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http://www.europrise.org The European HIV Prevention R&D Network Europrise SCIENCE UPDATE Issued on every Monday - The Companion to the EUROPRISE NEWS (issued on every Friday) - Sources: NCBI (NLM/NIH) – MIS (Medical Intelligence Solutions) - Scope: S&T information of interest to any organisation involved in HIV/AIDS PREVENTION RESEARCH AND INNOVATION – i.e. research re science, technology, strategies and policies - Distribution: free Search Term: “HIV” Selection ratio: +/- 65/100 - This bulletin includes references of articles that are already printed as well as e-publications (ahead of print) ----------------------------------------------------------------------------------------------------INTENDED FOR WIDE DISTRIBUTION: TELL YOUR FRIENDS! EUROPRISE SCIENCE UPDATE N° 12-21 21 May 2012 Main Headings Adjuvants 7 Diagnosis 7 Epidemiology 8 Health economics 10 Immunology 11 Immunology, other vaccines Microbicides 20 Other prevention, circumcision Other prevention, condoms Other prevention, PrEP 25 Pathology, cellular & molecular Pathology, coinfections 32 Therapeutic vaccines 33 Therapy, ART 34 Therapy, cell 35 Vaccines 36 Vaccines, research 36 Virology 41 Virology, resistance 46 20 22 23 27 ---------------------------------------------------------------------------------------------------------Free for Distribution to any interested reader - EUROPRISE contact: [email protected] Searching within this issue use EDIT / SEARCH function of MS Word Accuracy of information depends on reliability of sources The Europrise members do not necessarily share the opinions expressed in the reported items EUROPRISE SCIENCE UPDATE 12-21 CONTENTS ADJUVANTS ......................................................................................................................................... 7 Effects of Adjuvants on IgG Subclasses Elicited by Virus-Like Particles ............................................................. 7 DIAGNOSIS........................................................................................................................................... 7 The Relationship Between HIV Testing and CD4 Counts at HIV Diagnosis Among Newly Diagnosed HIV-1 Patients in Japan .............................................................................................................................................. 7 EPIDEMIOLOGY ................................................................................................................................. 8 HIV Prevalence Among Men Who Have Sex With Men in New Zealand 1985-2009: 25 Years of Public Health Monitoring ....................................................................................................................................................... 8 Disparities in Sexually Transmitted Disease Rates Across the "Eight Americas" ............................................... 8 High HIV Incidence and Socio-Behavioral Risk Patterns in Fishing Communities on the Shores of Lake Victoria, Uganda............................................................................................................................................................. 9 HIV: A Growing Concern in the Elderly Population ......................................................................................... 10 HEALTH ECONOMICS .................................................................................................................... 10 Does Donor Assistance for Hiv Respond to Media Pressure?.......................................................................... 10 Cost-Effectiveness of the National HIV/AIDS Strategy (NHAS) Goal of Increasing Linkage to Care for HIVInfected Persons ............................................................................................................................................ 11 IMMUNOLOGY ................................................................................................................................. 11 Characteristics of Cd8+ T Cell Subsets in Chinese Patients With Chronic Hiv Infection During Initial Art ........ 11 The Development of CD4 Binding Site Antibodies During HIV-1 Infection ...................................................... 12 Specific CD8+ T Cell Responses Correlate With Control of SIV Replication in Mauritian Cynomolgus Macaques ....................................................................................................................................................................... 12 HLA-C and HIV-1: Friends or Foes? ................................................................................................................. 13 Psoriasis Patients Are Enriched for Genetic Variants That Protect Against HIV-1 Disease............................... 13 Immunogenetic Surveillance of HIV/AIDS ...................................................................................................... 14 HIV-1 Capture and Antigen Presentation by Dendritic Cells: Enhanced Viral Capture Does Not Correlate With Better T Cell Activation .................................................................................................................................. 15 Single-Cell Level Response of HIV-Specific and CMV-Specific CD4 T Cells Correlate With Viral Control in Chronic HIV-1 Subtype A Infection ................................................................................................................. 15 Aminopeptidase Substrate Preference Affects HIV Epitope Presentation and Predicts Immune Escape Patterns in HIV-Infected Individuals ............................................................................................................... 16 -------------------------------------------------------------------------------------------------------------- 2 / 57 EUROPRISE SCIENCE UPDATE 12-21 T Cell Independent Secondary Antibody Responses to the Envelope Protein of Simian Immunodeficiency Virus............................................................................................................................................................... 17 Vitamin D Inhibits Human Immunodeficiency Virus Type 1 and Mycobacterium Tuberculosis Infection in Macrophages Through the Induction of Autophagy ....................................................................................... 17 Vpu Mediates IRF3 Depletion During HIV Infection by a Lysosomal-Dependent Mechanism ......................... 18 CD56+ T Cells Inhibit HIV-1 Infection of Macrophages .................................................................................... 18 Iron Metabolism and the Innate Immune Response to Infection ................................................................... 19 Association of HLA-Alleles With the Immune Regulation of Chronic Viral Infections ...................................... 19 IMMUNOLOGY, OTHER VACCINES ............................................................................................ 20 Commentary: Immunologic Response to Oral Polio Vaccine in Human Immunodeficiency Virus-Infected and Uninfected Zimbabwean Children .................................................................................................................. 20 MICROBICIDES ................................................................................................................................ 20 Future Prospects and Perspectives on Microbicides ....................................................................................... 20 Reformulated Tenofovir Gel for Use As a Dual Compartment Microbicide ..................................................... 21 Colposcopy: Still Useful in Microbicide Safety Trials? ..................................................................................... 21 OTHER PREVENTION, CIRCUMCISION .................................................................................... 22 Biological Basis for the Protective Effect Conferred by Male Circumcision Against HIV Infection ................... 22 A Cost-Effective Analysis of Male Circumcision for the Prevention of HIV in the United States ...................... 22 OTHER PREVENTION, CONDOMS.............................................................................................. 23 Condom Use Among Female Sex Workers and Their Non-Commercial Partners: Effects of a Sexual Risk Intervention in Two Mexican Cities ................................................................................................................ 23 Condom Migration Resulting From Circumcision, Microbicides and Vaccines: Brief Review and Methodological Considerations...................................................................................................................... 23 Condom Use Errors and Problems: a Global View .......................................................................................... 24 Condom Social Marketing in Sub-Saharan Africa and the Total Market Approach ......................................... 24 OTHER PREVENTION, PREP ....................................................................................................... 25 Limited SHIV Env Diversification in Macaques Failing Oral Antiretroviral Pre-Exposure Prophylaxis .............. 25 New Success With Microbicides and Pre-Exposure Prophylaxis for Human Immunodeficiency Virus (HIV): Is Female-Controlled Prevention the Answer to the HIV Epidemic? ................................................................... 26 AIDS Research. FDA Panel Recommends Anti-HIV Drug for Prevention .......................................................... 26 -------------------------------------------------------------------------------------------------------------- 3 / 57 EUROPRISE SCIENCE UPDATE 12-21 Willingness of Kenyan HIV-1 Serodiscordant Couples to Use Antiretroviral Based HIV-1 Prevention Strategies ....................................................................................................................................................................... 26 PATHOLOGY, CELLULAR & MOLECULAR ............................................................................... 27 Mitochondrial DNA: a Proinflammatory 'Enemy From Within' During HIV Infection? .................................... 27 Macroautophagy Regulation During HIV-1 Infection of CD4+ T Cells and Macrophages ................................. 27 Superresolution Imaging of HIV in Infected Cells With FlAsH-PALM ............................................................... 28 Differential Regulation of the Let-7 Family of MicroRNAs in CD4+ T Cells Alters IL-10 Expression .................. 28 IFN-Lambda Inhibits HIV-1 Integration and Post-Transcriptional Events in Vitro, but There Is Only Limited in Vivo Repression of Viral Production ............................................................................................................... 29 The Molecular Basis of HIV Entry ................................................................................................................... 30 Genetic and Functional Analysis of HIV-1 Nef Gene Derived From LTNP Children: Association of Attenuated Variants With Slow Progression to Pediatric AIDS .......................................................................................... 30 Cis-Acting Determinants of 7SL RNA Packaging by HIV-1 ................................................................................ 31 Expression of Human Endogenous Retrovirus Type-K (HML-2) Is Activated by the Tat Protein of HIV-1 ......... 31 PATHOLOGY, COINFECTIONS..................................................................................................... 32 Hepatitis B, C and D Coinfection in HIV-Infected Patients: Prevalence and Progress ...................................... 32 HIV-HBV Coinfection--a Global Challenge ....................................................................................................... 32 Seroepidemiology of Novel Influenza A (H1N1) Infection Among HIV-Infected Patients in the Era of Highly Active Antiretroviral Therapy ......................................................................................................................... 33 THERAPEUTIC VACCINES ............................................................................................................ 33 Single DermaVir Immunization: Dose-Dependent Expansion of Precursor/Memory T Cells Against All HIV Antigens in HIV-1 Infected Individuals ............................................................................................................ 33 THERAPY, ART ................................................................................................................................ 34 The Elvitegravir Quad Pill: the First Once-Daily Dual-Target Anti-HIV Tablet .................................................. 34 Are There Benefits to Starting Antiretroviral Therapy During Primary HIV Infection? Conclusions From the Seattle Primary Infection Cohort Vary by Control Group ................................................................................ 35 THERAPY, CELL ............................................................................................................................... 35 CD34-Derived Dendritic Cells Transfected Ex Vivo With HIV-Gag MRNA Induce Polyfunctional T-Cell Responses in Nonhuman Primates ................................................................................................................. 35 VACCINES .......................................................................................................................................... 36 -------------------------------------------------------------------------------------------------------------- 4 / 57 EUROPRISE SCIENCE UPDATE 12-21 Use of Conjoint Analysis to Assess HIV Vaccine Acceptability: Feasibility of an Innovation in the Assessment of Consumer Health-Care Preferences ........................................................................................................... 36 VACCINES, RESEARCH................................................................................................................... 36 Macaque Studies of Vaccine and Microbicide Combinations for Preventing HIV-1 Sexual Transmission ........ 36 Improved Outlook on HIV-1 Prevention and Vaccine Development ............................................................... 37 International Network for Comparison of HIV Neutralization Assays: The NeutNet Report II ........................ 37 PD-1/PD-L1 Blockade Can Enhance HIV-1 Gag-Specific T Cell Immunity Elicited by Dendritic Cell-Directed Lentiviral Vaccines ......................................................................................................................................... 38 Accelerated Heterologous Adenovirus Prime-Boost SIV Vaccine in Neonatal Rhesus Monkeys ..................... 39 Gene-Based Vaccination With a Mis-Matched Envelope Protects Against Simian Immunodeficiency Virus Infection in Non-Human Primates .................................................................................................................. 39 Association of Enhanced HIV-1 Neutralization by a Single Y681H Substitution in Gp41 With Increased Gp120CD4 Interaction and Macrophage Infectivity .................................................................................................. 40 HIV Vaccine Design: the Neutralizing Antibody Conundrum ........................................................................... 40 VIROLOGY ......................................................................................................................................... 41 Co-Evolution of Primate SAMHD1 and Lentivirus Vpx Leads to the Loss of the Vpx Gene in HIV-1 Ancestor .. 41 Refined Identification of Neutralization-Resistant HIV-1 CRF02_AG Viruses .................................................. 41 [Study on the Molecular-Epidemiological Characteristics of HIV-1 in Shenzhen, 1992-2008].......................... 42 HIV-2 Infection in Providence, Rhode Island From 2002 to 2011 .................................................................... 42 Characterization of HIV-1 Subtypes and Drug Resistance Mutations Among Individuals Infected With HIV in Georgia .......................................................................................................................................................... 43 Meeting the Challenge of HIV Diversity: Strategies to Mitigate the Impact of HIV-1 Genetic Heterogeneity on Performance of Nucleic Acid Testing Assays ................................................................................................... 43 Feline Immunodeficiency Virus in South America .......................................................................................... 44 Viral Diversity and Diversification of Major Non-Structural Genes Vif, Vpr, Vpu, Tat Exon 1 and Rev Exon 1 During Primary HIV-1 Subtype C Infection ...................................................................................................... 44 Two Unique Recombinant Forms Identified in Incident HIV-1 Infections in Thai Blood Donors ...................... 45 New Insights into the Evolutionary Rate of HIV-1 at the Within-Host and Epidemiological Levels ................. 45 VIROLOGY, RESISTANCE .............................................................................................................. 46 Virological Response and HIV Drug Resistance 12 Months After Antiretroviral Therapy Initiation at 2 Clinics in Nigeria ........................................................................................................................................................... 46 -------------------------------------------------------------------------------------------------------------- 5 / 57 EUROPRISE SCIENCE UPDATE 12-21 Surveillance of HIV Drug Resistance in Children Receiving Antiretroviral Therapy: A Pilot Study of the World Health Organization's Generic Protocol in Maputo, Mozambique .................................................................. 46 Prevalence of HIV Drug Resistance Before and 1 Year After Treatment Initiation in 4 Sites in the Malawi Antiretroviral Treatment Program ................................................................................................................. 47 A Retrospective Survey of HIV Drug Resistance Among Patients 1 Year After Initiation of Antiretroviral Therapy at 4 Clinics in Malawi ........................................................................................................................ 47 Initial Virologic Response and HIV Drug Resistance Among HIV-Infected Individuals Initiating First-Line Antiretroviral Therapy at 2 Clinics in Chennai and Mumbai, India .................................................................. 48 Surveillance of Transmitted HIV Drug Resistance Using Matched Plasma and Dried Blood Spot Specimens From Voluntary Counseling and Testing Sites in Ho Chi Minh City, Vietnam, 2007-2008 ................................ 48 Transmitted Antiretroviral Drug Resistance Among Drug-Naive Female Sex Workers With Recent Infection in Kampala, Uganda ........................................................................................................................................... 49 Surveillance of Transmitted HIV-1 Drug Resistance in Gauteng and KwaZulu-Natal Provinces, South Africa, 2005-2009 ...................................................................................................................................................... 49 Transmitted HIV Drug Resistance Among Drug-Naive Subjects Recently Infected With HIV in Mexico City: A World Health Organization Survey to Classify Resistance and to Field Test Two Alternative Patient Enrollment Methods......................................................................................................................................................... 50 Prevalence of Transmitted HIV Drug Resistance Among Newly Diagnosed Antiretroviral Therapy-Naive Pregnant Women in Lilongwe and Blantyre, Malawi ...................................................................................... 50 Surveys of Transmitted HIV Drug Resistance in 7 Geographic Regions in China, 2008-2009 ........................... 51 Surveillance of Transmitted Drug-Resistant HIV Among Young Pregnant Women in Ouagadougou, Burkina Faso................................................................................................................................................................ 51 Monitoring of Early Warning Indicators for HIV Drug Resistance in Antiretroviral Therapy Clinics in Zimbabwe ....................................................................................................................................................................... 52 Combining Cohort Analysis and Monitoring of HIV Early-Warning Indicators of Drug Resistance to Assess Antiretroviral Therapy Services in Vietnam .................................................................................................... 52 Experience in Piloting HIV Drug Resistance Early Warning Indicators to Improve the Antiretroviral Program in Papua New Guinea ......................................................................................................................................... 53 Monitoring HIV Drug Resistance Using Early Warning Indicators in China: Results From a Pilot Survey Conducted in 2008 ......................................................................................................................................... 53 Implementing Early-Warning Indicators of HIV Drug Resistance in the Caribbean ......................................... 54 HIV Drug Resistance Early Warning Indicators in Cohorts of Individuals Starting Antiretroviral Therapy Between 2004 and 2009: World Health Organization Global Report From 50 Countries ................................ 54 Genotyping External Quality Assurance in the World Health Organization HIV Drug Resistance Laboratory Network During 2007-2010 ............................................................................................................................ 55 Are Countries Using Global Fund Support to Implement HIV Drug Resistance Surveillance? A Review of Funded HIV Grants ......................................................................................................................................... 55 -------------------------------------------------------------------------------------------------------------- 6 / 57 EUROPRISE SCIENCE UPDATE 12-21 Update on World Health Organization HIV Drug Resistance Prevention and Assessment Strategy: 2004-2011 ....................................................................................................................................................................... 56 The World Health Organization HIV Drug Resistance Prevention and Assessment Strategy: Global, Regional, and Country Progress ..................................................................................................................................... 56 [Survey on the Transmission of HIV Drug Resistance in Kunming, Yunnan Province in 2010] ......................... 56 Prevalence of Drug Resistance and Associated Mutations in a Population of HIV-1(+) Puerto Ricans: 20062010 ............................................................................................................................................................... 57 -------------------------------------------- Adjuvants 1 Adjuvants Effects of Adjuvants on IgG Subclasses Elicited by Virus-Like Particles VISCIANO ML, Tagliamonte M, Tornesello ML, Buonaguro FM, and Buonaguro L J Transl Med ,10, 4 ,2012 AD - Lab, of Molecular Biology and Viral Oncogenesis, Istituto Nazionale Tumori Fond, G, Pascale, NaplesItaly eng PT Journal Article PT - Research Support, Non-U.S. Gov't BACKGROUND: Virus-Like Particles (VLPs) represent an efficient strategy to present and deliver conformational antigens to the immune system, inducing both arms of the adaptive immune response. Moreover, their particulate structure surrounded by cell membrane provides an adjuvanted effect to VLP-based immunizations. In the present study, the elicitation of different patterns of IgG subclasses by VLPs, administered in CpG ODN1826 or poly(I:C) adjuvants, has been evaluated in an animal model. RESULTS: Adjuvanted VLPs elicited a higher titer of total specific IgG compared to VLPs alone. Furthermore, while VLPs alone induced a balanced TH2 pattern, VLPs formulated with either adjuvant elicited a TH1-biased IgG subclasses (IgG2a and IgG3), with poly(I:C) more potent than CpG ODN1826. CONCLUSIONS: The results confirmed that adjuvants efficiently improve antigen immunogenicity and represent a suitable strategy to skew the adaptive immune response toward the differentiation of the desired T helper subset, also using VLPs as antigen Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 221900 Diagnosis 2 Diagnosis The Relationship Between HIV Testing and CD4 Counts at HIV Diagnosis Among Newly Diagnosed HIV-1 Patients in Japan TAKANO M, Okada M, Oka S, and Wagatsuma Y Int J STD AIDS ,23 (4), 262-266 ,2012 AD - Social and Environmental Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba -------------------------------------------------------------------------------------------------------------- 7 / 57 EUROPRISE SCIENCE UPDATE 12-21 eng PT - Journal Article The aim of this study was to investigate the factors relating to CD4 level at HIV diagnosis and HIV testing behaviour. Participants were newly diagnosed patients (n = 654) in Japan from 2000 to 2005. Around 75% of participants were diagnosed at hospital and clinics. Mean CD4 counts at diagnosis through voluntary HIV testing, screening tests and testing due to concomitant sexually transmitted infection (STI) were 368, 336 and 316 cells/muL, respectively. In contrast, the mean CD4 count where testing was due to the presence of HIV-related clinical symptoms was 151 cells/muL (P < 0.0001). Compared with those diagnosed at their first HIV test, those who had undertaken multiple HIV tests prior to diagnosis showed CD4 counts that increased significantly (P < 0.0001) in relation to the number of tests undertaken: CD4 count at first test was 232 cells/muL, second test 346 cells/muL and third or additional tests 439 cells/muL. According to our results, HIV testing policy that promotes HIV testing in medical settings and among STI patients is needed to facilitate earlier HIV diagnosis in Japan Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 581950 Epidemiology 3 Epidemiology HIV Prevalence Among Men Who Have Sex With Men in New Zealand 1985-2009: 25 Years of Public Health Monitoring SAXTON PJ, Dickson NP, McAllister SM, Hughes AJ, and Sharples K Int J STD AIDS ,23 (4), 274-279 ,2012 AD - AIDS Epidemiology Group, Department of Preventive and Social Medicine, University of Otago Medical School, PO Box 913, Dunedin eng PT - Journal Article Annual population-based estimates of the number of men who have sex with men (MSM) with diagnosed HIV infection (HIV prevalence pool), and the proportion of all MSM this represents (HIV prevalence), have been insufficiently described over the long term. We investigated the dynamic effects of ongoing HIV diagnoses, lower mortality due to treatment and growth in the MSM population over time on these two epidemic indicators using national HIV/AIDS surveillance data in New Zealand, 1985-2009. The diagnosed HIV prevalence pool rose 79% between 1989 and 1999, and 137% between 1999 and 2009. Estimates of diagnosed HIV prevalence as a proportion of MSM were 0.2% of MSM in 1985, and were between 1.5% and 5.0% of MSM by 2009. New Zealand continues to have a relatively lowprevalence HIV epidemic among MSM; however, the number of MSM living with diagnosed infection is growing rapidly 25 years after HIV testing was introduced Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 581952 -----------------------------------------------------4 Epidemiology Disparities in Sexually Transmitted Disease Rates Across the "Eight Americas" CHESSON HW, Kent CK, Owusu-Edusei K Jr, Leichliter JS, and Aral SO Sex Transm Dis ,39 (6), 458-464 ,2012 AD - From the Division of STD Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA -------------------------------------------------------------------------------------------------------------- 8 / 57 EUROPRISE SCIENCE UPDATE 12-21 eng PT - Journal Article BACKGROUND: : The purpose of this study was to examine rates of 3 bacterial sexually transmitted diseases (STDs; syphilis, gonorrhea, and chlamydia) in 8 subpopulations (known as the "eight Americas") defined by race and a small number of county-level sociodemographic and geographical characteristics. The eight Americas are (1) Asians and Pacific Islanders in specific counties; (2) Northland low-income rural white; (3) Middle America; (4) Low-income whites in Appalachia and Mississippi Valley; (5) Western Native American; (6) Black middle America; (7) Southern low-income rural black; and (8) High-risk urban black. METHODS: : A list of the counties comprising each of the eight Americas was obtained from the corresponding author of the original eight Americas project, which examined disparities in mortality rates across the eight Americas. Using county-level STD surveillance data, we calculated syphilis, gonorrhea, and chlamydia rates (new cases per 100,000) for each of the eight Americas. RESULTS: : Reported STD rates varied substantially across the eight Americas. STD rates were generally lowest in Americas 1 and 2 and highest in Americas 6, 7, and 8. CONCLUSIONS: : Although disparities in STDs across the eight Americas are generally similar to the well-established disparities in STDs across race/ethnicity, the grouping of counties into the eight Americas does offer additional insight into disparities in STDs in the United States. The high STD rates we found for black Middle America are consistent with the assertion that sexual networks and social factors are important drivers of racial disparities in STDs Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 592832 -----------------------------------------------------5 Epidemiology High HIV Incidence and Socio-Behavioral Risk Patterns in Fishing Communities on the Shores of Lake Victoria, Uganda SEELEY J, Nakiyingi-Miiro J, Kamali A, Mpendo J, Asiki G, Abaasa A, De Bont J, Nielsen L, and Kaleebu P Sex Transm Dis ,39 (6), 433-439 ,2012 AD - From the *Medical Research Council/Uganda Virus Research Institute, Uganda Research Unit on AIDS, Entebbe, Uganda; daggerSchool of International Development, University of East Anglia, Norwich, United Kingdom; double daggerLondon School of Hygiene and Tropical Medicine, London, United Kingdom; section signUganda Virus Research Institute, Entebbe, Uganda; paragraph signUganda Virus Research Institute/International Aids Vaccine Initiative HIV Vaccine Program, Entebbe, Uganda; and ||International AIDS Vaccine Initiative, New York, NY eng PT - Journal Article BACKGROUND: : We report on HIV acquisition and its associated risk factors in 5 fishing communities on the shores of Lake Victoria in Uganda. A cohort of 1000 HIV-uninfected at-risk volunteers aged 13 to 49 years were recruited in 2009 and followed up for 18 months. METHODS: : At enrollment and semiannual visits, socio-demographic and risk behavior data were collected through a structured questionnaire and blood samples tested for HIV and syphilis. Detailed life histories were collected from 78 volunteers using in-depth interviews. RESULTS: : Of the 1000 volunteers enrolled, 919 (91.9%) were followed up, with 762 (76.2%) reaching the study end points (either seroconverted or completed 4 visits). There were 59 incident cases in 1205.6 person-years at risk (PYAR), resulting in an incidence rate of 4.9 (95% CI = 3.8 to 6.3) per 100 PYAR. The highest HIV incidence rates were among those working in bars (9.8/100 PYAR [4.7-20.6]), protestants (8.6/100 PYAR [5.8-12.7]), those aged 13 to 24 years (7.5/100 PYAR [5.2-11.0]), and new immigrants (6.6/100 PYAR [4.9-8.9]). HIV infection was independently associated with being young (adjusted hazard ratio (aHR) = 2.5 [95% CI = 1.3-4.9]), reporting genital sores/discharge recently (aHR = 2.8 [1.6-5.0]), regular alcohol consumption (aHR = 3.3 [1.6-6.1]), use of marijuana (aHR = 2.9 [1.0-8.0]), cigarette smoking (aHR = 3.6 [1.4-9.3]), and religion (compared with Catholics, Protestants had aHR = 2.7 [1.4-5.3] and Muslims had aHR = 2.3 [1.1-4.8]). CONCLUSIONS: : These fishing communities experienced high HIV infection, -------------------------------------------------------------------------------------------------------------- 9 / 57 EUROPRISE SCIENCE UPDATE 12-21 which was mainly explained by high-risk behavior. There is an urgent need to target HIV prevention and research efforts to this vulnerable and neglected group Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 592828 -----------------------------------------------------6 Epidemiology HIV: A Growing Concern in the Elderly Population VOURI SM and Blaszczyk AT Consult Pharm ,27 (5), 358-364 ,2012 AD St Louis College of Pharmacy, St Louis, Missouri eng PT - Journal Article HIV infections are a growing concern in the elderly as a result of improvements in therapeutics and monitoring, which have extended the life span for this HIV-infected population. Elderly patients potentially are more complicated to treat than younger HIV-infected individuals because of comorbidities and the physiological effects of aging on pharmacokinetics and pharmacodynamics. The patient, a 67-year-old African-American HIV-infected male, presents to the transitional care unit of university-affiliated hospital refusing to take medications and undergo laboratory testing, including blood draws. This patient's treatment is further complicated by poor renal function, medications with potential interactions, and a recent diagnosis of depression. This case demonstrates treatment and monitoring of an elderly patient with HIV and reveals the complications associated with this disease state. Specifically, it identifies nonadherence to medications and a lack of laboratory results, which affect the efficacy of treatment and monitoring, medication adjustments based on metabolism and renal excretion, monitoring of adverse effects of HIV and antiretro-viral therapy, and comorbid conditions that may be linked to HIV and antiretroviral therapy such as depression and bone disease. Education on HIV medications, monitoring, and standards of care for pharmacists working with the geriatric population is warranted and should be emphasized as the HIV-infected elderly population continues to grow Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 591980 Health economics 7 Health economics Does Donor Assistance for Hiv Respond to Media Pressure? CARMIGNANI F, Lordan G, and Tang KK Health Econ ,21 Suppl 1, 18-32 ,2012 AD - Department of Accounting, Finance, and Economics, Griffith Business School, Griffith University, Brisbane, Australia; School of Economics, The University of Queensland, Brisbane, Australia eng PT - Journal Article HIV/AIDS is a heavily mediatised disease. In this article, we test whether media attention is affecting donors' disbursement of aid for HIV to African countries. We use information available on the number of articles and press documents on HIV issues and other health concerns published in donor countries to construct a proxy of media coverage. This proxy is then included as an explanatory variable in a regression of aid for HIV to Africa. After controlling for several donor characteristics, we find that greater media coverage increases aid disbursement. This may be good news for the HIV campaign but -------------------------------------------------------------------------------------------------------------- 10 / 57 EUROPRISE SCIENCE UPDATE 12-21 may result in displacement effects to the extent that other diseases that cause greater mortality and morbidity receive less media coverage than HIV and thus less health aid. Copyright (c) 2012 John Wiley & Sons, Ltd Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 555998 -----------------------------------------------------8 Health economics Cost-Effectiveness of the National HIV/AIDS Strategy (NHAS) Goal of Increasing Linkage to Care for HIV-Infected Persons GOPALAPPA C, Farnham PG, Hutchinson AB, and Sansom SL J Acquir Immune Defic Syndr ,2012 AD Centers for Disease Control and Prevention, Atlanta, GA ENG PT - JOURNAL ARTICLE BACKGROUND:: One of the goals of the National HIV/AIDS Strategy (NHAS) is to increase the proportion of HIV-infected individuals linked to care within 3 months of diagnosis (early linkage) from 65% to 85%. Earlier access to care, and eventually, to treatment, increases life-expectancy and quality of life for HIV-infected persons. However, longer treatment is also associated with higher costs, especially for antiretroviral drugs. We evaluated the cost-effectiveness of achieving the NHAS goal and estimated the maximum cost that HIV programs could spend on linkage to care and remain cost-effective. METHODS:: We used the Progression and Transmission of HIV/AIDS (PATH) model to estimate the effects on life-measures and costs associated with increasing early linkage to care from 65% to 85%. We estimated an incremental cost-effectiveness ratio as the additional cost required to reach the target divided by the quality-adjusted life-years (QALYs) gained and assumed that programs costing $100,000 or less per QALY gained are cost-effective. RESULTS:: Achieving the NHAS linkage-to-care goal increased life expectancy by 0.4 years and delayed the onset of AIDS by 1.2 years on average for every HIV-diagnosed person. Increasing early linkage to care cost an extra $62,200 per qualityadjusted life-year gained, considering only benefits to index persons. The maximum that could be cost-effectively spent on early linkage-to-care interventions was approximately $ 5,100 per HIVdiagnosed person. CONCLUSION:: Considerable investment can be cost-effectively made to achieve the NHAS goal on early linkage to care Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 580563 Immunology 9 Immunology Characteristics of Cd8+ T Cell Subsets in Chinese Patients With Chronic Hiv Infection During Initial Art JIAO Y. and Wu, H. ,Geneva; Switzerland, 1396 ,2011 Capital Medical University, Beijing, China 4th Congress of European Microbiologists of the Federation of European Microbiological Societies (FEMS)Geneva; Switzerland- June 29, 2011http://www2.kenes.com/fems2011/pages/home.aspx ------------------------------------------------------------------------------------------------------------------------------------------------------------------- 11 / 57 EUROPRISE SCIENCE UPDATE 12-21 10 Immunology The Development of CD4 Binding Site Antibodies During HIV-1 Infection LYNCH RM, Tran L, Louder MK, Schmidt SD, Cohen M, Dersimonian R, Euler Z, Gray ES, Abdool Karim S, Kirchherr J, Montefiori DC, Sibeko S, Soderberg K, Tomaras G, Yang ZY, Nabel GJ, Schuitemaker H, Morris L, Haynes BF, and Mascola JR J Virol ,2012 AD Vaccine Research Center ENG PT - JOURNAL ARTICLE Broadly neutralizing antibodies to the CD4 binding site (CD4bs) of gp120 are generated by some HIV-1 infected individuals, but little is known about the prevalence and evolution of this antibody response during the course of HIV-1 infection. We analyzed the sera of 113 HIV-1 seroconverters from three cohorts for binding to a panel of gp120 core proteins and their corresponding CD4bs knockout mutants. Among sera collected between 99-258 weeks post HIV-1 infection, 88% contained antibodies to the CD4bs and 47% contained antibodies to resurfaced stabilized core (RSC) probes that react preferentially with broadly neutralizing CD4bs antibodies (BNCD4) such as monoclonal antibodies (mAbs) VRC01 and VRC-CH31. Analysis of longitudinal serum samples from a subset of 18 subjects revealed that CD4bs antibodies to gp120 arose within the first 4 to 16 weeks of infection, while the development of RSC-reactive antibodies was more varied, occurring between 10 and 152 weeks post HIV-1 infection. Despite the presence of these antibodies, serum neutralization mediated by RSC-reactive antibodies was only detected in sera from a few donors infected for more than three years. Thus, CD4bs antibodies that bind a VRC01-like epitope are often induced during HIV-1 infection, but the level and potency required to mediate serum neutralization may take years to develop. An improved understanding of the immunological factors associated with the development and maturation of neutralizing CD4bs antibodies during HIV-1 infection may provide insights into the requirements for eliciting this response by vaccination Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 573869 -----------------------------------------------------11 Immunology Specific CD8+ T Cell Responses Correlate With Control of SIV Replication in Mauritian Cynomolgus Macaques BUDDE ML, Greene JM, Chin EN, Ericsen AJ, Scarlotta M, Cain BT, Pham NH, Becker EA, Harris M, Weinfurter JT, O'Connor SL, Piatak M Jr, Lifson JD, Gostick E, Price DA, Friedrich TC, and O'Connor DH J Virol ,2012 AD - Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin, USA ENG PT - JOURNAL ARTICLE Specific major histocompatibility complex (MHC) class I alleles are associated with an increased frequency of spontaneous control of human and simian immunodeficiency viruses (HIV and SIV). The mechanism of control is thought to involve MHC class I-restricted CD8+ T cells, but it is not clear whether particular CD8+ T cell responses or a broad repertoire of epitope-specific CD8+ T cell populations (termed T cell breadth) is principally responsible for mediating immunologic control. To test the hypothesis that heterozygous macaques control SIV replication as a function of superior T cell breadth, we infected MHC-homozygous and MHC-heterozygous cynomolgus macaques with the pathogenic virus SIVmac239. As measured by IFN-gamma ELISPOT in blood, T cell breadth did not differ significantly between homozygotes and heterozygotes. Surprisingly, macaques that controlled SIV replication, regardless of their MHC zygosity, shared durable T cell responses against similar -------------------------------------------------------------------------------------------------------------- 12 / 57 EUROPRISE SCIENCE UPDATE 12-21 regions of Nef. While the limited genetic variability in these animals prevents us from making generalizations about the importance of Nef-specific T cell responses in controlling HIV, these results suggest that the T cell-mediated control of virus replication that we observed is more likely the consequence of targeting specificity rather than T cell breadth Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 573864 -----------------------------------------------------12 Immunology HLA-C and HIV-1: Friends or Foes? ZIPETO D and Beretta A Retrovirology ,9 (1), 39 ,2012 ENG PT - JOURNAL ARTICLE ABSTRACT: The major histocompatibility complex class I protein HLA-C plays a crucial role as a molecule capable of sending inhibitory signals to both natural killer (NK) cells and cytotoxic T lymphocytes (CTL) via binding to killer cell Ig-like receptors (KIR). Recently HLA-C has been recognized as a key molecule in the immune control of HIV-1. Expression of HLA-C is modulated by a microRNA binding site. HLA-C alleles that bear substitutions in the microRNA binding site are more expressed at the cell surface and associated with the control of HIV-1 viral load, suggesting a role of HLA-C in the presentation of antigenic peptides to CTLs. This review highlights the role of HLA-C in association with HIV-1 viral load, but also addresses the contradiction of the association between high cell surface expression of an inhibitory molecule and strong cell-mediated immunity. To explore additional mechanisms of control of HIV-1 replication by HLA-C, we address specific features of the molecule, like its tendency to be expressed as open conformer upon cell activation, which endows it with a unique capacity to associate with other cell surface molecules as well as with HIV-1 proteins Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 571741 -----------------------------------------------------13 Immunology Psoriasis Patients Are Enriched for Genetic Variants That Protect Against HIV-1 Disease CHEN H, Hayashi G, Lai OY, Dilthey A, Kuebler PJ, Wong TV, Martin MP, Fernandez Vina MA, McVean G, Wabl M, Leslie KS, Maurer T, Martin JN, Deeks SG, Carrington M, Bowcock AM, Nixon DF, and Liao W PLoS Genet ,8 (2), e1002514 ,2012 AD - Department of Dermatology, University of California San Francisco, San Francisco, California, United States of America eng PT - Journal Article An important paradigm in evolutionary genetics is that of a delicate balance between genetic variants that favorably boost host control of infection but which may unfavorably increase susceptibility to autoimmune disease. Here, we investigated whether patients with psoriasis, a common immunemediated disease of the skin, are enriched for genetic variants that limit the ability of HIV-1 virus to replicate after infection. We analyzed the HLA class I and class II alleles of 1,727 Caucasian psoriasis cases and 3,581 controls and found that psoriasis patients are significantly more likely than controls to have gene variants that are protective against HIV-1 disease. This includes several HLA class I alleles associated with HIV-1 control; amino acid residues at HLA-B positions 67, 70, and 97 that mediate HIV-1 peptide binding; and the deletion polymorphism rs67384697 associated with high -------------------------------------------------------------------------------------------------------------- 13 / 57 EUROPRISE SCIENCE UPDATE 12-21 surface expression of HLA-C. We also found that the compound genotype KIR3DS1 plus HLA-B Bw480I, which respectively encode a natural killer cell activating receptor and its putative ligand, significantly increased psoriasis susceptibility. This compound genotype has also been associated with delay of progression to AIDS. Together, our results suggest that genetic variants that contribute to anti-viral immunity may predispose to the development of psoriasis Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 577363 -----------------------------------------------------14 Immunology Immunogenetic Surveillance of HIV/AIDS STEPHENS HA Infect Genet Evol ,2012 AD - UCL Centre for Nephrology and the Anthony Nolan Laboratories Royal Free Hospital Rowland Hill Street London NW3 2PF UK ENG PT - JOURNAL ARTICLE Evolutionary pressure by viruses is most likely responsible for the extraordinary allelic polymorphism of genes encoding class I human leukocyte antigens (HLA) and killer immunoglobulin-like receptors (KIR). Such genetic diversity has functional implications for the immune response to viruses and generates population-based variations in HLA class I allele frequencies and KIR gene profiles. The HIV-1 virus has relatively recently established itself as a major human pathogen, rapidly diversifying into a variety of phylogenetic subtypes or clades (A-G) and recombinants in different populations. HIV-1 clade C is the most common subtype in circulation accounting for 48% of all infections, followed by HIV-1 clades A and B which are responsible for 13% and 11% of infections in the current pandemic, respectively. Candidate gene studies of large cohorts of predominantly HIV-1 clade B but also clades C and A infected patients, have consistently shown significant associations between certain HLA class I alleles namely HLA-B *57, B *58, B *27, B *51 and relatively low viraemia. However, there is evidence that other associations between HLA-B *15, B *18 or B *53 and levels of HIV-1 viraemia are clade-specific. Recent genome-wide association studies of HIV-1 clade B exposed cohorts have confirmed that HLA-B, which is the most polymorphic locus in the human genome, is the major genetic locus contributing to immune control of viraemia. Moreover, the presence of natural killer cell receptors encoded by KIR-3DL1 and 3DS1 genes together with certain HLA class I alleles carrying the KIR target motif Bw4Ile80, provides an enhanced ability to control HIV-1 viraemia in some individuals. It is likely that rapid co-evolution of HIV-1 immune escape variants together with an adjustment of human immune response gene profiles has occurred in some exposed populations. Taken together, immunogenetic surveillance of HIV-1 exposed cohorts has revealed important correlates of natural immunity, which could provide a rational platform for the design and testing of future vaccines aimed at controlling the current AIDS pandemic Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 575339 ------------------------------------------------------ -------------------------------------------------------------------------------------------------------------- 14 / 57 EUROPRISE SCIENCE UPDATE 12-21 15 Immunology HIV-1 Capture and Antigen Presentation by Dendritic Cells: Enhanced Viral Capture Does Not Correlate With Better T Cell Activation RODRIGUEZ-PLATA MT, Urrutia A, Cardinaud S, Buzon MJ, Izquierdo-Useros N, Prado JG, Puertas MC, Erkizia I, Coulon PG, Cedeno S, Clotet B, Moris A, and Martinez-Picado J J Immunol ,2012 AD - Institut de Recerca de la SIDA IrsiCaixa, Hospital Germans Trias i Pujol, Universitat Autonoma de Barcelona, 08916 Badalona, Spain; ENG PT - JOURNAL ARTICLE During HIV-1 infection, dendritic cells (DC) facilitate dissemination of HIV-1 while trying to trigger adaptive antiviral immune responses. We examined whether increased HIV-1 capture in DC matured with LPS results in more efficient Ag presentation to HIV-1-specific CD4(+) and CD8(+) T cells. To block the DC-mediated trans-infection of HIV-1 and maximize Ag loading, we also evaluated a noninfectious integrase-deficient HIV-1 isolate, HIV(NL4-3DeltaIN). We showed that higher viral capture of DC did not guarantee better Ag presentation or T cell activation. Greater HIV(NL4-3) uptake by fully LPS-matured DC resulted in higher viral transmission to target cells but poorer stimulation of HIV-1-specific CD4(+) and CD8(+) T cells. Conversely, maturation of DC with LPS during, but not before, viral loading enhanced both HLA-I and HLA-II HIV-1-derived Ag presentation. In contrast, DC maturation with the clinical-grade mixture consisting of IL-1beta, TNF-alpha, IL-6, and PGE(2) during viral uptake only stimulated HIV-1-specific CD8(+) T cells. Hence, DC maturation state, activation stimulus, and time lag between DC maturation and Ag loading impact HIV-1 capture and virus Ag presentation. Our results demonstrate a dissociation between the capacity to capture HIV-1 and to present viral Ags. Integrase-deficient HIV(NL4-3DeltaIN) was also efficiently captured and presented by DC through the HLA-I and HLA-II pathways but in the absence of viral dissemination. HIV(NL4-3DeltaIN) seems to be an attractive candidate to be explored. These results provide new insights into DC biology and have implications in the optimization of DC-based immunotherapy against HIV-1 infection Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 581857 -----------------------------------------------------16 Immunology Single-Cell Level Response of HIV-Specific and CMV-Specific CD4 T Cells Correlate With Viral Control in Chronic HIV-1 Subtype A Infection ELLER MA, Eller LA, Ratto-Kim S, Ouma BJ, Lo V, de Souza M, Guwatudde D, Nails B, Michael NL, WabwireMangen F, Robb ML, Marovich MA, Sandberg JK, and Currier JR J Acquir Immune Defic Syndr ,2012 AD - US Military HIV Research Program, Silver Spring, USA Makerere University Walter Reed Project, Kampala, Uganda Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand Makerere University School of Public Health, Kampala, Uganda Karolinska Institutet Center for Infectious Medicine, Stockholm, Sweden ENG PT - JOURNAL ARTICLE BACKGROUND:: and Objective: HIV-1 subtype A is the second most prevalent subtype globally and is associated with reduced viral load, higher CD4 absolute counts, and slower disease progression. In order to study the possible role of T cells associated with better outcome, we examined CD4 and CD8 T cell responses against HIV-1 and CMV in Ugandans infected with subtype A HIV-1. METHODS AND -------------------------------------------------------------------------------------------------------------- 15 / 57 EUROPRISE SCIENCE UPDATE 12-21 RESULTS:: T cell responses were investigated using flow cytometry and novel subtype A variant inclusive peptide sets designed for this evaluation. CD4 T cell responses focused primarily on Gag, whereas CD8 T cell responses were broadly directed against Gag, gp41, and Nef VIP sets. CD4 T cells primarily responded with IFN-gamma, while CD8 cells were more diverse with degranulation (CD107a), IFN-gamma, and MIP-1beta production. No relationship was observed between CD8 T cell responses and the HIV-1 load. Similarly, the frequency of CD4 T cells responding to these antigens did not associate with viral control. However, in CD4 T cells responding against Gag or CMV, the IFNgamma intensity, indicative of production at the single-cell level, was inversely proportional to viral load. No significant relationship was found between T cell effector/memory phenotype and viral control. CONCLUSIONS:: The per cell production of IFN-gamma in CD4 T cells responding to HIV-1 or CMV correlated with viral control in chronic HIV-1 subtype A infection. These data suggest that quantitative aspects at the single-cell level may be more important than the frequency of antigenspecific CD4 T cells in HIV-1 subtype A infection control Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 580564 -----------------------------------------------------17 Immunology Aminopeptidase Substrate Preference Affects HIV Epitope Presentation and Predicts Immune Escape Patterns in HIV-Infected Individuals ZHANG SC, Martin E, Shimada M, Godfrey SB, Fricke J, Locastro S, Lai NY, Liebesny P, Carlson JM, Brumme CJ, Ogbechie OA, Chen H, Walker BD, Brumme ZL, Kavanagh DG, and Le Gall S J Immunol ,2012 AD - Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129; ENG PT - JOURNAL ARTICLE Viruses evade immune detection partly through immune-associated mutations. Analyses of HIV sequences derived from infected individuals have identified numerous examples of HLA-associated mutations within or adjacent to T cell epitopes, but the potential impact of most mutations on epitope production and presentation remains unclear. The multistep breakdown of proteins into epitopes includes trimming of N-extended peptides into epitopes by aminopeptidases before loading onto MHC class I molecules. Definition of sequence signatures that modulate epitope production would lead to a better understanding of factors driving viral evolution and immune escape at the population level. In this study, we identified cytosolic aminopeptidases cleavage preferences in primary cells and its impact on HIV Ag degradation into epitopes in primary human cell extracts by mass spectrometry and on epitope presentation to CTL. We observed a hierarchy of preferred amino acid cleavage by cytosolic aminopeptidases. We demonstrated that flanking mutations producing more or less cleavable motifs can increase or decrease epitope production and presentation by up to 14-fold. We found that the efficiency of epitope production correlates with cleavability of flanking residues. These in vitro findings were supported by in vivo population-level analyses of clinically derived viral sequences from 1134 antiretroviral-naive HIV-infected individuals: HLA-associated mutations immune pressures drove the selection of residues that are less cleavable by aminopeptidases predominantly at N-flanking sites, leading to reduced epitope production and immune recognition. These results underscore an important and widespread role of Ag processing mutations in HIV immune escape and identify molecular mechanisms underlying impaired epitope presentation Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 586036 ------------------------------------------------------------------------------------------------------------------------------------------------------------------- 16 / 57 EUROPRISE SCIENCE UPDATE 12-21 18 Immunology T Cell Independent Secondary Antibody Responses to the Envelope Protein of Simian Immunodeficiency Virus NABI G, Temchura V, Grossmann C, Kuate S, Tenbusch M, and Uberla K Retrovirology ,9 (1), 42 ,2012 ENG PT - JOURNAL ARTICLE ABSTRACT: BACKGROUND: During human (HIV) and simian (SIV) immunodeficiency virus infection, loss of CD4+ T cells and progression to AIDS are associated with a decline in antibody titers to the viral Gag protein, while antibodies to the Env protein remain high, suggesting a T cell independent antibody response to Env. RESULTS: To explore differential regulation of Gag and Env antibody responses, immunocompetent BALB/c and T cell deficient nude mice were immunized with virus like particles (VLP) of simian immunodeficiency virus or adenoviral vectors expressing SIV Gag and Env. High levels of antibodies against Gag and Env could only be induced in immunocompetent mice, but not in the immunodeficient mice. Thus, neither cells expressing Env after adenoviral gene transfer nor VLPs induce a T cell independent primary anti-Env antibody response. However, secondary B cell responses to Env, but not to Gag, were observed in immunodeficient mice after transfer of primed B cells and boosting with VLPs or adenoviral vectors expressing Gag and Env. This T cell independent secondary antibody response to Env was reduced after stimulation with VLPs modified to contain monomeric membrane bound gp130 surface subunit of Env and undetectable after injection of soluble gp130. CONCLUSIONS: Membrane-bound trimeric Env seems to be responsible for the maintenance of high levels of anti-Env antibodies during progression to AIDS. This T cell independent secondary antibody response may prevent T cell-dependent affinity maturation and thus contribute to viral immune escape by favoring persistence of non-protective antibodies Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 583867 -----------------------------------------------------19 Immunology Vitamin D Inhibits Human Immunodeficiency Virus Type 1 and Mycobacterium Tuberculosis Infection in Macrophages Through the Induction of Autophagy CAMPBELL GR and Spector SA PLoS Pathog ,8 (5), e1002689 ,2012 AD - Department of Pediatrics, Division of Infectious Diseases, University of California San Diego, La Jolla, California, United States of America eng PT - Journal Article Low vitamin D levels in human immunodeficiency virus type-1 (HIV) infected persons are associated with more rapid disease progression and increased risk for Mycobacterium tuberculosis infection. We have previously shown that 1alpha,25-dihydroxycholecalciferol (1,25D3), the active form of vitamin D, inhibits HIV replication in human macrophages through the induction of autophagy. In this study, we report that physiological concentrations of 1,25D3 induce the production of the human cathelicidin microbial peptide (CAMP) and autophagic flux in HIV and M. tuberculosis co-infected human macrophages which inhibits mycobacterial growth and the replication of HIV. Using RNA interference for Beclin-1 and the autophagy-related 5 homologue, combined with the chemical inhibitors of autophagic flux, bafilomycin A(1), an inhibitor of autophagosome-lysosome fusion and subsequent acidification, and SID 26681509 an inhibitor of the lysosome hydrolase cathepsin L, we show that the 1,25D3-mediated inhibition of HIV replication and mycobacterial growth during single infection or dual infection is dependent not only upon the induction of autophagy, but also through phagosomal -------------------------------------------------------------------------------------------------------------- 17 / 57 EUROPRISE SCIENCE UPDATE 12-21 maturation. Moreover, through the use of RNA interference for CAMP, we demonstrate that cathelicidin is essential for the 1,25D3 induced autophagic flux and inhibition of HIV replication and mycobacterial growth. The present findings provide a biological explanation for the benefits and importance of vitamin D sufficiency in HIV and M. tuberculosis-infected persons, and provide new insights into novel approaches to prevent and treat HIV infection and related opportunistic infections Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 589721 -----------------------------------------------------20 Immunology Vpu Mediates IRF3 Depletion During HIV Infection by a LysosomalDependent Mechanism DOEHLE BP, Chang K, Rustagi A, McNevin J, McElrath MJ, and Gale M Jr J Virol ,2012 AD - University of Washington School of Medicine, Department of Immunology Seattle, WA 98195 ENG PT - JOURNAL ARTICLE HIV has evolved sophisticated mechanisms to avoid restriction by intracellular innate immune defenses that otherwise serve to control acute viral infection and virus dissemination. Innate defenses are triggered when pathogen recognition receptor (PRR) proteins of the host cell engage pathogenassociated molecule patterns (PAMPs) present in viral products. Interferon regulatory factor (IRF)3 plays a central role in PRR signaling of innate immunity to drive the expression of type I interferon (IFN) and interferon-stimulated genes (ISGs), including a variety of HIV restriction factors, that serve to limit viral replication directly and/or program adaptive immunity. Productive infection of T cells by HIV is dependent upon the targeted proteolysis of IRF3 that occurs through a virus-directed mechanism that results in suppression of innate immune defenses. However, the mechanisms by which HIV controls innate immune signaling and IRF3 function are not defined. Here, we examined the innate immune response induced by HIV strains identified through their differential control of PRR signaling. We identified viruses that unlike typical circulating HIV strains lack the ability to degrade IRF3. Our studies show that IRF3 regulation maps specifically to the HIV accessory protein Vpu. We define a molecular interaction between Vpu and IRF3 that redirects IRF3 to the endolysosome for proteolytic degradation, thus allowing HIV to avoid the innate antiviral immune response. Our studies reveal Vpu as an important IRF3 regulator that supports acute HIV infection through innate immune suppression. These observations define the Vpu/IRF3 interface as a novel target for therapeutic strategies aimed at enhancing the immune response to HIV Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 593165 -----------------------------------------------------21 Immunology CD56+ T Cells Inhibit HIV-1 Infection of Macrophages HOU W, Ye L, and Ho WZ J Leukoc Biol ,2012 AD *Animal Biosafety Level 3 Laboratory/Center for Animal Experiment ENG PT - JOURNAL ARTICLE CD56+ T cells, the crucial component of the host innate immune system, play an important role in defense against viral infections. We investigated the noncytolytic anti-HIV-1 activity of primary CD56+ T cells. SNs collected from CD56+ T cell cultures inhibited HIV-1 infection and replication. This CD56+ T SN-------------------------------------------------------------------------------------------------------------- 18 / 57 EUROPRISE SCIENCE UPDATE 12-21 mediated anti-HIV-1 activity was broad-spectrum, as CD56+ T SNs could inhibit infections by laboratory-adapted and clinical strains of HIV-1. The antibody to IFN-gamma could partially block the CD56+ T SN-mediated anti-HIV effect. Investigation of mechanism(s) of the CD56+ T cell action on HIV-1 showed that although CD56+ T SN had little effect on HIV-1 entry coreceptor CCR5 expression, CD56+ T SN induced the expression of CC-chemokines, the ligands for CCR5. The antibodies to CCchemokines also significantly blocked CD56+ T SN-mediated anti-HIV activity. Furthermore, CD56+ T SN up-regulated the expression of STAT-1/-2 and enhanced the expression of IRF1, -3, -7, and -9, resulting in the induction of endogenous IFN-alpha/beta expression in macrophages. Moreover, CD56+ T SN up-regulated intracellular expression of APOBEC3G/3F, the recently identified HIV-1 restriction factors. These findings provide compelling evidence that CD56+ T cells may have a critical role in innate immunity against HIV-1 infection Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 591692 -----------------------------------------------------22 Immunology Iron Metabolism and the Innate Immune Response to Infection JOHNSON EE and Wessling-Resnick M Microbes Infect ,14 (3), 207-216 ,2012 AD - John Carroll University, Department of Biology, 20700 North Park Boulevard, University Heights, OH 44118, USA eng PT Journal Article PT Research Support, N.I.H., Extramural PT - Review Host antimicrobial mechanisms reduce iron availability to pathogens. Iron proteins influencing the innate immune response include hepcidin, lactoferrin, siderocalin, haptoglobin, hemopexin, Nramp1, ferroportin and the transferrin receptor. Numerous global health threats are influenced by iron status and provide examples of our growing understanding of the connections between infection and iron metabolism Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 033148 -----------------------------------------------------23 Immunology Association of HLA-Alleles With the Immune Regulation of Chronic Viral Infections ELAHI S and Horton H Int J Biochem Cell Biol ,2012 AD - Viral Vaccine Program, Seattle Biomedical Research Institute (Seattle Biomed), Seattle, WA 98109, USA ENG PT - JOURNAL ARTICLE Cytotoxic CD8T lymphocytes (CTLs) have an astonishing ability to eliminate pathogen-infected cells. However, if uncontrolled, these CTLs could cause devastating pathology to host tissues. CD8(+) effector T cells, therefore, interact with antigen-presenting cells and other immune cells, such as regulatory T cells (Tregs), to regulate further on-site expansion and differentiation of the effector cells. This ensures protection of the host with minimal bystander pathological consequences. During prolonged chronic infections CTLs, however, often lose effector function. Induction of multiple -------------------------------------------------------------------------------------------------------------- 19 / 57 EUROPRISE SCIENCE UPDATE 12-21 inhibitory pathways is emerging as a major regulator converting effector CTLs into exhausted CTLs during chronic viral infections such as HIV, HCV and HBV. The mechanisms involved in induction of exhaustion during chronic viral infections are the focus of this article. Blockade of inhibitory pathways could potentially restore functional capabilities to exhausted CTLs and represents a potential immune-based intervention in chronic viral infections Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 595281 Immunology, other vaccines 24 Immunology, other vaccines Commentary: Immunologic Response to Oral Polio Vaccine in Human Immunodeficiency Virus-Infected and Uninfected Zimbabwean Children JAFARI HS Pediatr Infect Dis J ,31 (2), 181-183 ,2012 AD - National Polio Surveillance Project, World Health Organization, India jafariha@npsuindiaorg eng PT Comment PT Journal ArticleLink : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 252205 ------------------------------------------------------ Microbicides 25 Microbicides Future Prospects and Perspectives on Microbicides ANTON PA Curr HIV Res ,10 (1), 113-115 ,2012 AD - David Geffen School of Medicine and Center for HIV Prevention Research, University of California Los Angeles, Los Angeles, CA, USA panton@mednetuclaedu eng PT Journal Article PT Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't As 'proof of concept' has now been well validated for topical microbicides, the progress has, appropriately, refined the questions of who, how, when and at what risk and cost. These are welcome challenges requiring intensified, cross-disciplinary responses. This is especially true in the areas of adherence and pharmacokinetic/pharmacodynamics (PK/PD) sampling and modeling to optimize preventive trials measuring "efficacy", which is well known to reduce when measured as "effectiveness" in realworld use. Intensified exploratory and Phase 1 safety trials to investigate acceptability, adherence, PK and ex vivo efficacy with drug-exposed tissue biopsies/compartment fluids even though they are complex in design, management, assays and monitoring are moving forward As well, great strides in recent efforts in a variety of delivery formulations are promising. These current and future efforts will provide potential insights earlier that at Phase IIb or III in the development pipeline -------------------------------------------------------------------------------------------------------------- 20 / 57 EUROPRISE SCIENCE UPDATE 12-21 Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 264086 -----------------------------------------------------26 Microbicides Reformulated Tenofovir Gel for Use As a Dual Compartment Microbicide DEZZUTTI CS, Rohan LC, Wang L, Uranker K, Shetler C, Cost M, Lynam JD, and Friend D J Antimicrob Chemother ,2012 AD - University of Pittsburgh, 204 Craft Avenue, Pittsburgh, PA 15213, USA ENG PT - JOURNAL ARTICLE OBJECTIVES: Coital use of 1% tenofovir gel was shown to be modestly effective at preventing HIV transmission when applied vaginally in the CAPRISA 004 trial. Because the gel is hyperosmolar, which would reduce the integrity of the epithelium and induce fluid movement into the lumen, rectal use may not be acceptable. This study evaluated the pre-clinical safety and efficacy of a reformulated (reduced osmolality) tenofovir gel product. METHODS: Reduced glycerine (RG)-tenofovir gel was compared with the original tenofovir gel for physiochemical characteristics, product safety and antiHIV-1 activity. RESULTS: The formulations were similar in all characteristics except for osmolality and spreadability/firmness. The RG-tenofovir gel had a 73% lower osmolality, a 29.6% increase in spreadability and a 27% decrease in firmness as compared with the original tenofovir gel. When applied to epithelial cell monolayers, tenofovir gel showed a transient reduction in the transepithelial resistance while the RG-tenofovir gel did not. Both gels retained ectocervical and colorectal explant viability. However, tenofovir gel treatment resulted in epithelial stripping that was absent after RGtenofovir gel treatment of the polarized explants. Anti-HIV-1 activity was confirmed by lack of HIV-1 infection in polarized explants treated with either gel as compared with the control explants. CONCLUSIONS: Reducing the osmolality of the tenofovir gel resulted in improved epithelial integrity, which suggests better safety upon rectal use. The improved gel safety did not compromise drug release or anti-HIV-1 activity. These data support the use of this gel as a dual compartment microbicide Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 581908 -----------------------------------------------------27 Microbicides Colposcopy: Still Useful in Microbicide Safety Trials? MAUCK CK, Weiner DH, Lai JJ, and Schwartz JL Sex Transm Dis ,39 (6), 465-469 ,2012 AD - From *CONRAD, Arlington,VA; and daggerFamily Health International 360, Durham, NC eng PT - Journal Article BACKGROUND: : Colposcopy is used to evaluate vaginal microbicides, but its link to risk of HIV is unknown. This reanalysis of 9 safety studies determined the impact of omitting colposcopy on the number of findings detected and assessed whether colposcopy was useful in identifying nonoxynol-9 (N-9) as an unsafe product in one study. METHODS: : Product-related findings seen with naked eye and colposcopy or by colposcopy alone were evaluated. Using data from one study, the ratio of findings in N-9 users to those in hydroxyethylcellulose (HEC) users was compared for findings seen by naked eye and colposcopy versus findings detected only by colposcopy. RESULTS: : Of the 403 finding observations in the 9 studies, 173 (43%) would have been missed without colposcopy. Data -------------------------------------------------------------------------------------------------------------- 21 / 57 EUROPRISE SCIENCE UPDATE 12-21 from the N-9/HEC study showed that without colposcopy, there would have been 7 times as many observations in the N-9 group as in the HEC group (63 vs. 9). With colposcopy, the N-9/HEC ratio was 13:9 or 1.4. Considering epithelial integrity, finding type, and size showed similar patterns, except that among the smallest findings (<5 mm), the N-9/HEC ratio was 1.2 by naked eye and nearly the same at 1.4 by colposcopy. CONCLUSION: : Colposcopy was not helpful in identifying an unsafe product: the conclusions reached using naked eye examination alone were more alarming regarding the safety of N-9 than reached by including colposcopy. Recommendations include: (1) naked eye examinations should be continued in microbicide studies; (2) colposcopy may be considered for early studies, such as first-in-human studies, but has no place in large studies; and (3) colposcopy should be replaced as soon as possible with a more objective validated biomarker of HIV risk Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 592833 ------------------------------------------------------ Other prevention, circumcision 28 Other prevention, circumcision Biological Basis for the Protective Effect Conferred by Male Circumcision Against HIV Infection MORRIS BJ and Wamai RG Int J STD AIDS ,23 (3), 153-159 ,2012 AD - Basic & Clinical Genomics Laboratory, School of Medical Sciences and Bosch Institute, University of Sydney, Sydney, NSW, Australia eng PT - Journal Article Here we provide an up-to-date review of research that explains why uncircumcised men are at higher risk of HIV infection. The inner foreskin is a mucosal epithelium deficient in protective keratin, yet rich in HIV target cells. Soon after sexual exposure to infected mucosal secretions of a HIV-positive partner, infected T-cells from the latter form viral synapses with keratinocytes and transfer HIV to Langerhans cells via dendrites that extend to just under the surface of the inner foreskin. The Langerhans cells with internalized HIV migrate to the basal epidermis and then pass HIV on to T-cells, thus leading to the systemic infection that ensues. Infection is exacerbated in inflammatory states associated with balanoposthitis, the presence of smegma and ulceration - including that caused by infection with herpes simplex virus type 2 and some other sexually transmitted infections (STIs). A high foreskin surface area and tearing of the foreskin or associated frenulum during sexual intercourse also facilitate HIV entry. Thus, by various means, the foreskin is the primary biological weak point that permits HIV infection during heterosexual intercourse. The biological findings could explain why male circumcision protects against HIV infection Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 581866 -----------------------------------------------------29 Other prevention, circumcision A Cost-Effective Analysis of Male Circumcision for the Prevention of HIV in the United States DRENNAN S. and Gala, R. ,San Diego, CA; USA ,2012 -------------------------------------------------------------------------------------------------------------- 22 / 57 EUROPRISE SCIENCE UPDATE 12-21 Ochsner Clinic Foundation, New Orleans, Louisiana 60th Annual Meeting of the American College of Obstetricians and Gynecologists (ACOG) San Diego, CA; USA6 May 2012 http://www.acog.org/About_ACOG/News_Room/News_Releases/2012/Awards_Presented_at_the_60 th_ACM Other prevention, condoms 30 Other prevention, condoms Condom Use Among Female Sex Workers and Their NonCommercial Partners: Effects of a Sexual Risk Intervention in Two Mexican Cities ULIBARRI MD, Strathdee SA, Lozada R, Staines-Orozco HS, Abramovitz D, Semple S, Martinez GA, and Patterson TL Int J STD AIDS ,23 (4), 229-234 ,2012 AD Department of Psychiatry eng PT - Journal Article The purpose of this study was to examine whether a brief behavioural intervention promoting condom use among female sex workers (FSWs) and their clients had the added benefit of increasing condom use among FSWs and their steady, non-commercial partners (e.g. husbands, boyfriends). Participants were 362 FSWs, aged >/=18 years, living in Tijuana or Ciudad Juarez, Mexico, who received a behavioural intervention to promote condom use with clients. Repeated-measures negative binomial regression was used to assess FSWs' condom use with steady partners versus clients across time. Results showed that FSWs engaged in unprotected sex with steady partners more than with their clients, and that the intervention changed FSWs' condom use with clients but not their steady partners. HIV-prevention interventions for FSWs should promote consistent condom use across partner type. Targeting couples rather than individuals may also be necessary Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 581944 -----------------------------------------------------31 Other prevention, condoms Condom Migration Resulting From Circumcision, Microbicides and Vaccines: Brief Review and Methodological Considerations CROSBY RA, Ricks J, and Young A Sex Health ,9 (1), 96-102 ,2012 AD - College of Public Health, University of Kentucky, 111 Washington Avenue, Lexington, KY 40536-0003, USA crosby@ukyedu eng PT Journal Article PT - Review OBJECTIVE: To provide an updated review of condom migration as a means of highlighting methodological issues for future studies of this behavioural issue. METHODS: Electronic searches of PubMed, MEDLINE and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases were carried out in October 2010 and updated in January 2011 for English-language articles published from 1994 onward. RESULTS: Evidence addressing condom migration from microbicides and vaccines is vastly underdeveloped, simply because these products are still experimental. In contrast, the more advanced evidence regarding male circumcision is hopeful because it suggests that -------------------------------------------------------------------------------------------------------------- 23 / 57 EUROPRISE SCIENCE UPDATE 12-21 migration may not be an overwhelming issue. Nonetheless, the entire body of empirical evidence on this question could be substantially expanded and improved. CONCLUSION: Until stronger evidence suggests that condom migration is unlikely, it is important to be mindful of the potential for condom migration to occur in response to biomedical interventions (circumcision, microbicides and vaccines) Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 348637 -----------------------------------------------------32 Other prevention, condoms Condom Use Errors and Problems: a Global View SANDERS SA, Yarber WL, Kaufman EL, Crosby RA, Graham CA, and Milhausen RR Sex Health ,9 (1), 81-95 ,2012 AD - The Kinsey Institute for Research in Sex, Gender, IN, USA sanders@indianaedu eng PT Journal Article PT - Review BACKGROUND: Significantly more research attention has been devoted to the consistency of condom use, with far fewer studies investigating condom use errors and problems. The purpose of this review was to present the frequency of various condom use errors and problems reported worldwide. METHODS: A systematic literature search was conducted for peer-reviewed articles, published in Englishlanguage journals between 1995 and 2011. RESULTS: Fifty articles representing 14 countries met criteria for inclusion. The most common errors included not using condoms throughout sex, not leaving space at the tip, not squeezing air from the tip, putting the condom on upside down, not using water-based lubricants and incorrect withdrawal. Frequent problems included breakage, slippage, leakage, condom-associated erection problems, and difficulties with fit and feel. Prevalence estimates showed great variation across studies. Prevalence varied as a function of the population studied and the period assessed. CONCLUSION: Condom use errors and problems are common worldwide, occurring across a wide spectrum of populations. Although breakage and slippage were most commonly investigated, the prevalence of other condom use errors and problems found in this review were substantially higher. As a framework for understanding the role of condom errors and problems in inadequate protection, we put forward a new model: the Condom Use Experience model. This model can be used to generate testable hypotheses for future research. Addressing condom use errors and problems in research and interventions is crucial to closing the gap between the perfect use and typical use of condoms Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 348636 -----------------------------------------------------33 Other prevention, condoms Condom Social Marketing in Sub-Saharan Africa and the Total Market Approach CHAPMAN S, Jafa K, Longfield K, Vielot N, Buszin J, Ngamkitpaiboon L, and Kays M Sex Health ,9 (1), 44-50 ,2012 AD - Population Services International, 1120 19th Street, NW #600, Washington, DC 20036, USA schapman@psiorg eng PT - Journal Article BACKGROUND: Social marketing interventions are important in developing nations. Both increasing use and shifting users from receiving subsidised condoms need to be pursued using a Total Market -------------------------------------------------------------------------------------------------------------- 24 / 57 EUROPRISE SCIENCE UPDATE 12-21 Approach (TMA). This paper reviews the performance of social marketing through a cross-country comparison of condom use, equity and market share, plus a case study illustrating how TMA can be applied. METHODS: Demographic and Health Survey data (1998-2007) provide condom use trends, concentration indices and sources of supply by gender for 11 African countries. Service delivery information and market research provide market share data for the same period. For the case study, two-yearly surveys (2001-09) are the source of condom trends, and retail audit data (2007-09) provide sustainability data. RESULTS: Among women, condom use with a non-marital, non-cohabiting partner increased significantly in 7 of 11 countries. For men, 5 of 11 countries showed an increase in condom use. Equity improved for men in five countries and was achieved in two; for women, equity improved in three. Most obtained condoms from shops and pharmacies; social marketing was the dominant source of supply. Data from Kenya were informative for TMA, showing improvements in condom use over time, but sustainability results were mixed and equity was not measured. Overall market value and number of brands increased; however, subsidies increased over time. CONCLUSIONS: Condom social marketing interventions have advanced and achieved the goals of improving use and making condoms available in the private sector. It is time to manage interventions and influence markets to improve equity and sustainability Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 348632 ------------------------------------------------------ Other prevention, PrEP 34 Other prevention, PrEP Limited SHIV Env Diversification in Macaques Failing Oral Antiretroviral Pre-Exposure Prophylaxis ZHENG Q, Ruone S, Switzer WM, Heneine W, and Garcia-Lerma JG Retrovirology ,9 (1), 40 ,2012 ENG PT - JOURNAL ARTICLE ABSTRACT: BACKGROUND: Pre-exposure prophylaxis (PrEP) with daily Truvada [a combination of emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF)] is a novel HIV prevention strategy recently found to prevent HIV transmission among men who have sex with men and heterosexual couples. Acute infection in persons who fail PrEP will inevitably occur under concurrent antiretroviral therapy, thus raising questions regarding the potential impact of PrEP on early viral dynamics. We investigated viral evolution dynamics in a macaque model of PrEP consisting of repeated rectal exposures to SHIV162P3 in the presence of PrEP. RESULTS: Two macaques were infected during daily or intermittent PrEP with FTC or FTC/TDF, and five were untreated controls. SHIV env sequence evolution was monitored by single genome amplification with phylogenetic and sequence analysis. Mean nucleotide divergence from transmitted founder viruses calculated 17 weeks (range = 12-20) post peak viremia was significantly lower in PrEP failures than in control animals (7.2 x 10-3 compared to 1.6 x 10-2 nucleotide substitutions per site per year, respectively, p < 0.0001). Mean virus diversity was also lower in PrEP failures after 17 weeks (0.13% vs. 0.53% in controls, p < 0.0001). CONCLUSIONS: Our results in a macaque model of acute HIV infection suggest that infection during PrEP limits early virus evolution likely because of a direct antiviral effect of PrEP and/or reduced target cell availability. Reduced virus diversification during early infection might enhance immune control by slowing the selection of escape mutants Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 571771 ------------------------------------------------------------------------------------------------------------------------------------------------------------------- 25 / 57 EUROPRISE SCIENCE UPDATE 12-21 35 Other prevention, PrEP New Success With Microbicides and Pre-Exposure Prophylaxis for Human Immunodeficiency Virus (HIV): Is Female-Controlled Prevention the Answer to the HIV Epidemic? OPOKU-ANANE J, Diouf K, and Nour NM Rev Obstet Gynecol ,5 (1), 50-55 ,2012 eng PT - Journal Article Women who cannot negotiate condom use with their partners, often due to socioeconomic factors and sexual abuse, have no means of preventing themselves from acquiring the human immunodeficiency virus (HIV). There is a need to develop HIV-preventive methods initiated and controlled by women. Microbicides and other pre-exposure prophylaxis may help fill that need. Although two decades of research on broad-spectrum microbicides have generally been disappointing, recent trials with HIVspecific agents have yielded promising initial results. A new era of clinical research involves novel biochemical prevention methods, including HIV-specific vaginal microbicides and oral antiretroviral chemoprophylaxis drugs (pre-exposure prophylaxis; PrEP) that may help provide more control for women Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 582127 -----------------------------------------------------36 Other prevention, PrEP AIDS Research. FDA Panel Recommends Anti-HIV Drug for Prevention COHEN J Science ,336 (6083), 792 ,2012 eng PT NewsLink : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 605725 -----------------------------------------------------37 Other prevention, PrEP Willingness of Kenyan HIV-1 Serodiscordant Couples to Use Antiretroviral Based HIV-1 Prevention Strategies HEFFRON R, Ngure K, Mugo N, Celum C, Kurth A, Curran K, and Baeten JM J Acquir Immune Defic Syndr ,2012 AD - Departments of 1Epidemiology 2Global Health, and 3Medicine, and 4School of Nursing, University of Washington, Seattle, WA, USA 5University of Nairobi, Nairobi, Kenya 6Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya 7Department of Obstetrics and Gynaecology, Kenyatta National Hospital, Nairobi, Kenya 8School of Nursing, New York University, New York, NY, USA ENG PT - JOURNAL ARTICLE INTRODUCTION:: Antiretroviral treatment (ART) and pre-exposure prophylaxis (PrEP) have demonstrated efficacy as new HIV-1 prevention approaches for HIV-1 serodiscordant couples. METHODS:: Among Kenyan HIV-1 serodiscordant heterosexual couples participating in a clinical trial -------------------------------------------------------------------------------------------------------------- 26 / 57 EUROPRISE SCIENCE UPDATE 12-21 of PrEP, we conducted a cross-sectional study and used descriptive statistical methods to explore couples' willingness to use antiretrovirals for HIV-1 prevention. The study was conducted prior to July 2011, when studies among heterosexual populations reported that ART and PrEP reduced HIV-1 risk. RESULTS:: For 181 couples in which the HIV-1 infected partner had a CD4 count >/=350 cells/muL and had not yet initiated ART (and thus did not qualify for ART under Kenyan guidelines), 60.2% of HIV-1 infected partners (69.4% of men and 57.9% of women) were willing to use early ART (at CD4 >/=350 cells/muL) for HIV-1 prevention. Among HIV-1 uninfected partners, 92.7% (93.8% of men and 86.1% of women) reported willingness to use PrEP. When given a hypothetical choice of early ART or PrEP for HIV-1 prevention, 52.5% of HIV-1 infected participants would prefer to initiate ART early and 56.9% of HIV-1 uninfected participants would prefer to use PrEP. CONCLUSIONS:: Nearly 40% of Kenyan HIV-1 infected individuals in known HIV-1 serodiscordant partnerships reported reservations about early ART initiation for HIV-1 prevention. PrEP interest in this PrEP-experienced population was high. Strategies to achieve high uptake and sustained adherence to ART and PrEP for HIV-1 prevention in HIV-1 serodiscordant couples will require responding to couples' preferences for prevention strategies Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 595872 ------------------------------------------------------ Pathology, cellular & molecular 38 Pathology, cellular & molecular Mitochondrial DNA: a Proinflammatory 'Enemy From Within' During HIV Infection? PINTI M, Mussini C, and Cossarizza A Cell Death Dis ,3, 307 ,2012 AD - Department of Biomedical Sciences, University of Modena and Reggio Emilia, via Campi 287, Modena 41125, Italy eng PT Journal ArticleLink : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 573036 -----------------------------------------------------39 Pathology, cellular & molecular Macroautophagy Regulation During HIV-1 Infection of CD4+ T Cells and Macrophages BOREL S, Espert L, and Biard-Piechaczyk M Front Immunol ,3, 97 ,2012 AD - Centre d'etudes d'agents Pathogenes et Biotechnologies pour la Sante, CNRS UMR5236, UM1/UM2 Montpellier, France eng PT - Journal Article Autophagy is an intracellular mechanism whereby pathogens, particularly viruses, are destroyed in autolysosomes after their entry into targets cells. Therefore, to survive and replicate in host cells, viruses have developed multiple strategies to either counteract or exploit this process. The aim of this review is to outline the known relationships between HIV-1 and autophagy in CD4+ T lymphocytes and macrophages, two main HIV-1 cell targets. The differential regulation of autophagy in these two -------------------------------------------------------------------------------------------------------------- 27 / 57 EUROPRISE SCIENCE UPDATE 12-21 cell-types is highlighted and its potential consequences in terms of viral replication and physiopathology discussed Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 586428 -----------------------------------------------------40 Pathology, cellular & molecular Superresolution Imaging of HIV in Infected Cells With FlAsH-PALM LELEK M, Di Nunzio F, Henriques R, Charneau P, Arhel N, and Zimmer C Proc Natl Acad Sci U S A ,2012 AD - Institut Pasteur, Groupe Imagerie et Modelisation; Centre National de la Recherche Scientifique Unite de Recherche Associee 2582 ENG PT - JOURNAL ARTICLE Imaging protein assemblies at molecular resolution without affecting biological function is a long-standing goal. The diffraction-limited resolution of conventional light microscopy ( approximately 200-300 nm) has been overcome by recent superresolution (SR) methods including techniques based on accurate localization of molecules exhibiting stochastic fluorescence; however, SR methods still suffer important restrictions inherent to the protein labeling strategies. Antibody labels are encumbered by variable specificity, limited commercial availability and affinity, and are mostly restricted to fixed cells. Fluorescent protein fusions, though compatible with live cell imaging, substantially increase protein size and can interfere with their biological activity. We demonstrate SR imaging of proteins tagged with small tetracysteine motifs and the fluorescein arsenical helix binder (FlAsH-PALM). We applied FlAsH-PALM to image the integrase enzyme (IN) of HIV in fixed and living cells under experimental conditions that fully preserved HIV infectivity. The obtained resolution ( approximately 30 nm) allowed us to characterize the distribution of IN within virions and intracellular complexes and to distinguish different HIV structural populations based on their morphology. We could thus discriminate approximately 100 nm long mature conical cores from immature Gag shells and observe that in infected cells cytoplasmic (but not nuclear) IN complexes display a morphology similar to the conical capsid. Together with the presence of capsid proteins, our data suggest that cytoplasmic IN is largely present in intact capsids and that these can be found deep within the cytoplasm. FlAsH-PALM opens the door to in vivo SR studies of microbial complexes within host cells and may help achieve truly molecular resolution Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 586087 -----------------------------------------------------41 Pathology, cellular & molecular Differential Regulation of the Let-7 Family of MicroRNAs in CD4+ T Cells Alters IL-10 Expression SWAMINATHAN S, Suzuki K, Seddiki N, Kaplan W, Cowley MJ, Hood CL, Clancy JL, Murray DD, Mendez C, Gelgor L, Anderson B, Roth N, Cooper DA, and Kelleher AD J Immunol ,2012 AD - Immunovirology Laboratory, St Vincent's Centre for Applied Medical Research, Darlinghurst, New South Wales 2010, Australia; ENG PT - JOURNAL ARTICLE MicroRNAs (miRNAs) are approximately 22-nt small RNAs that are important regulators of mRNA turnover and translation. Recent studies have shown the importance of the miRNA pathway in HIV-1 -------------------------------------------------------------------------------------------------------------- 28 / 57 EUROPRISE SCIENCE UPDATE 12-21 infection, particularly in maintaining latency. Our initial in vitro studies demonstrated that HIV-1infected HUT78 cells expressed significantly higher IL-10 levels compared with uninfected cultures. IL-10 plays an important role in the dysregulated cytotoxic T cell response to HIV-1, and in silico algorithms suggested that let-7 miRNAs target IL10 mRNA. In a time course experiment, we demonstrated that let-7 miRNAs fall rapidly following HIV-1 infection in HUT78 cells with concomitant rises in IL-10. To show a direct link between let-7 and IL-10, forced overexpression of let-7 miRNAs resulted in significantly reduced IL-10 levels, whereas inhibition of the function of these miRNAs increased IL-10. To demonstrate the relevance of these results, we focused our attention on CD4(+) T cells from uninfected healthy controls, chronic HIV-1-infected patients, and long-term nonprogressors. We characterized miRNA changes in CD4(+) T cells from these three groups and demonstrated that let-7 miRNAs were highly expressed in CD4(+) T cells from healthy controls and let-7 miRNAs were significantly decreased in chronic HIV-1 infected compared with both healthy controls and long-term nonprogressors. We describe a novel mechanism whereby IL-10 levels can be potentially modulated by changes to let-7 miRNAs. In HIV-1 infection, the decrease in let-7 miRNAs may result in an increase in IL-10 from CD4(+) T cells and provide the virus with an important survival advantage by manipulating the host immune response Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 586040 -----------------------------------------------------42 Pathology, cellular & molecular IFN-Lambda Inhibits HIV-1 Integration and Post-Transcriptional Events in Vitro, but There Is Only Limited in Vivo Repression of Viral Production TIAN RR, Guo HX, Wei JF, Yang CK, He SH, and Wang JH Antiviral Res ,2012 AD - Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China ENG PT - JOURNAL ARTICLE The lambda interferons (IL-28a, 28b, and IL-29) inhibit the replication of many viruses, but their role in the inhibition of HIV-1 infection remains unclear. During this study, we monitored IL-29 production in HIV-1 infected individuals and analyzed the in vitro and in vivo inhibition of HIV-1 production. Prior treatment with IL-28a or IL-29 induced an antiviral state in cultured primary T-cells, which suppressed HIV-1 integration and post-transcriptional events. The antiviral factors MxA, OAS, and PKR were up-regulated. In HIV-1 infected patients, IL-29 level was increased along with the depletion of CD4(+) T-cells in peripheral blood, while the elevated IL-29 did not show a significantly negative correlation with viral load. Further analysis of HIV-1 infected individuals showed that IL-29 was positively correlated with IFN-beta and anti-inflammatory cytokine IL-10, and was negatively correlated with IFN-gamma, which might suggest that IFN-lambda participates in modulating antiviral immune responses during HIV-1 infection in vivo. Together, although IFN-lambda impeded HIV-1 infection of T-cells in vitro, IFN-lambda showed only limited in vivo repression of viral production. The modulation of IFN-lambda on inflammatory factors might be worthy for further concentrating on for better understanding the host immune response during HIV-1 infection Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 584351 ------------------------------------------------------ -------------------------------------------------------------------------------------------------------------- 29 / 57 EUROPRISE SCIENCE UPDATE 12-21 43 Pathology, cellular & molecular The Molecular Basis of HIV Entry KLASSE PJ Cell Microbiol ,2012 AD - Department of Microbiology and Immunology, Cornell University, Weill Cornell Medical College, 1300 York Avenue, Box 62, New York, NY, 10065-4896 ENG PT - JOURNAL ARTICLE Infection by HIV starts when the virus attaches to a susceptible cell. For viral replication to continue, the viral envelope must fuse with a cellular membrane, thereby delivering the viral core to the cytoplasm, where the RNA genome is reverse-transcribed. The key players in this entry by fusion are the envelope glycoprotein, on the viral side, and CD4 and a co-receptor, CCR5 or CXCR4, on the cellular side. Here, the interplay of these molecules is reviewed from cell-biological, structural, mechanistic, and modeling-based perspectives. Hypotheses are evaluated regarding the cellular compartment for entry, the transfer of virus through direct cell-to-cell contact, the sequence of molecular events, and the number of molecules involved on each side of the virus-cell divide. An emerging theme is the heterogeneity among the entry mediators on both sides, a diversity that affects the efficacy of entry inhibitors, be they small-molecule ligands, peptides, or neutralizing antibodies. These insights inform rational strategies for therapy as well as vaccination Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 583677 -----------------------------------------------------44 Pathology, cellular & molecular Genetic and Functional Analysis of HIV-1 Nef Gene Derived From LTNP Children: Association of Attenuated Variants With Slow Progression to Pediatric AIDS CORRO G, Rocco C, De Candia C, Catano G, Turk G, Aulicino P, Bologna R, and Sen L AIDS Res Hum Retroviruses ,2012 AD - Hospital de Pediatria J P Garrahan, Laboratorio de Biologia Celular y Retrovirus - CONICET (Consejo Nacional de Investigaciones Cientificas y Tecnicas), Buenos Aires, Argentina; gcorro2@gmailcom ENG PT - JOURNAL ARTICLE Background. Among persons infected by HIV-1, the rate of progression to AIDS is multi-factorial being affected by host and viral factors, including the HIV-encoded negative factor (Nef). Our aim was to define whether variations in the nef gene as well as its functions may be associated with slower HIV disease course in infected children. Methods. Proviral HIV-1 nef gene was cloned, sequenced and compared in children with contrasting disease course: 10 long-term non-progressors (LTNP) and 6 rapid progressor (RP). CD4 and MHC-I downmodulation ability of nef alleles derived from LTNP and RP children were analyzed. Results. We observed that only one of our 10 LTNP had a protective genetic background, and out of them, 40% had defective nef genes, carrying substitutions at the (AWLEAQ56-61) and the (Rxx22-24) domains, and that those alleles were unable of downregulate CD4 and MHC-I. The emergence or presence of Nef L58V substitution was associated with viral attenuation, indicated by a reduction in HIV viral loads, a persistent preservation of CD4+ T cell counts and lack of AIDS related symptoms. Conclusions. Our results demonstrate that HIV-1 perinatally infected children carrying functionally defective nef HIV-1 strains have prolonged asymptomatic phases without therapy, suggesting a relevant role of CD4 and MHC-I downmodulation Nef domains on in vivo HIV-1 pathogenesis and pediatric immunodeficiency outcome Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 583022 -------------------------------------------------------------------------------------------------------------- 30 / 57 EUROPRISE SCIENCE UPDATE 12-21 -----------------------------------------------------45 Pathology, cellular & molecular Cis-Acting Determinants of 7SL RNA Packaging by HIV-1 KEENE SE and Telesnitsky A J Virol ,2012 AD - Department of Microbiology and Immunology, University of Michigan, Ann Arbor ENG PT - JOURNAL ARTICLE The host noncoding RNA 7SL is highly enriched in the virions of retroviruses. Here, we examined the regions of 7SL that mediate packaging by HIV-1. Both the Alu domain and the S domain were sufficient to mediate specific packaging when expressed separately as truncations of 7SL. However, while the Alu domain competed with endogenous 7SL for packaging in proportion to Gag, the S domain was packaged additively, implying that the Alu and S domains are packaged via separate mechanisms and that the Alu domain is packaged by the same mechanism as endogenous 7SL. Further truncations of the Alu domain or mutation of the Alu domain helix 5c region significantly reduced packaging efficiency, implicating helix 5c as critical for packaging, reinforcing the finding that 7SL packaging is highly selective, and confirming that 7SL is not passively acquired. Surprisingly, when the Alu domain was mutated so that it no longer contained a binding site for the SRP protein heterodimer SRP9/14, it was no longer packaged in a competitive manner, but instead was packaged additively with endogenous 7SL. These data support a model in which 7SL RNA is packaged via interactions between Gag and a 7SL RNA structure that exists transiently at a discrete stage of SRP biogenesis. Our data further indicate that a secondary "additive" pathway exists that can result in the packaging of certain 7SL derivatives in molar excess to endogenously packaged 7SL Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 593161 -----------------------------------------------------46 Pathology, cellular & molecular Expression of Human Endogenous Retrovirus Type-K (HML-2) Is Activated by the Tat Protein of HIV-1 GONZALEZ-HERNANDEZ MJ, Swanson MD, Contreras-Galindo R, Cookinham S, King SR, Noel RJ Jr, Kaplan MH, and Markovitz DM J Virol ,2012 AD Department of Internal Medicine ENG PT - JOURNAL ARTICLE Human Endogenous Retroviruses (HERVs) make up 8% of the human genome. Expression of HERV-K (HML-2), the family of HERVs that most recently entered the genome, is tightly regulated but becomes markedly increased following infection with HIV-1. To better understand the mechanisms involved in this activation, we explored the role of the HIV-1 Tat protein in inducing expression of these endogenous retroviral genes. Administration of recombinant HIV-1 Tat protein caused a 13-fold increase in HERV-K (HML-2) gag RNA transcripts in Jurkat T cells and a 10-fold increase in primary lymphocytes, and expression of the HERV-K (HML-2) rec and np9 oncogenes was also markedly increased. This activation was seen especially in lymphocytes and monocytic cells, the natural hosts for HIV-1 infection. Luciferase reporter gene assays demonstrated that the effect of Tat on HERV-K (HML-2) expression occurred at the level of the transcriptional promoter. The transcription factors NF-kappaB and NF-AT contribute to the Tat-induced activation of the promoter, as shown by chromatin immunoprecipitation assays, mutational analysis of the HERV-K (HML-2) LTR, and treatments with agents that inhibit NF-kappaB or NF-AT activation. These studies demonstrate that -------------------------------------------------------------------------------------------------------------- 31 / 57 EUROPRISE SCIENCE UPDATE 12-21 HIV-1 Tat plays an important role in activating expression of HERV-K (HML-2) in the setting of HIV-1 infection Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 593154 Pathology, coinfections 47 Pathology, coinfections Hepatitis B, C and D Coinfection in HIV-Infected Patients: Prevalence and Progress IONESCU B and Mihaescu G Roum Arch Microbiol Immunol ,70 (3), 129-133 ,2011 AD - University of Bucharest, Faculty of Biology, Microbiology and Immunology Department, Bucharest, Romania bogdanionescu87@yahoocom eng PT - Journal Article The HAART therapy has improved life expectancy enabling long latency conditions caused by the hepatitis viruses that became the leading cause of death in HIV infected patients. In this study a group of 300 patients aged from 18 to 63 years were selected in order to assess the prevalence and consequences of HIV and the hepatitis B (HBV), C (HCV) and D (HDV) viruses coinfections. Study groups were designed for each coinfection. These groups were in turn divided in case groups formed of coinfected participants and control groups consisting of mono-infected participants. This classification was obtained by testing the participants for the presence of specific infection markers using the ELISA technique. As a result, in regard to the HIV/HBV coinfection the study group consisted of 16 coinfected participants and 114 HBV-infected participants resulting in a prevalence of the coinfection of 14%. In the case of the HIV/HDV coinfection the study group consisted of 5 coinfected participants and 45 HDV-infected participants. The prevalence of the HIV/HCV coinfection was 25% out of the 170 HCV-infected participants. The effect of the coinfections on the expression and levels of the infection markers was analyzed in constrast to those encountered in the case of the mono-infection. The observed changes in the expression of the specific hepatitis markers indicate the impact of the coinfection with HIV on the progression of the hepatitis infections. In addition, the inadequate immune response towards the hepatitis viruses in the case of the coinfected participants leads to the development of cirrhosis and end stage liver disease Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 570927 -----------------------------------------------------48 Pathology, coinfections HIV-HBV Coinfection--a Global Challenge KOURTIS AP, Bulterys M, Hu DJ, and Jamieson DJ N Engl J Med ,366 (19), 1749-1752 ,2012 AD - Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, USA eng PT Journal ArticleLink : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 571198 -------------------------------------------------------------------------------------------------------------- 32 / 57 EUROPRISE SCIENCE UPDATE 12-21 -----------------------------------------------------49 Pathology, coinfections Seroepidemiology of Novel Influenza A (H1N1) Infection Among HIV-Infected Patients in the Era of Highly Active Antiretroviral Therapy HUNG CC, Zhao TL, Sun HY, Yang YF, Su YC, Chang SF, Liu WC, Wu CH, Chang SY, and Chang SC J Microbiol Immunol Infect ,2012 AD - Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan ENG PT - JOURNAL ARTICLE BACKGROUND: The seroprevalence and seroincidence of novel influenza A infection among HIV-infected patients, who were believed to have more severe outcomes than healthy individuals, are rarely investigated in the era of highly active antiretroviral therapy (HAART). Our aim was to determine the seroprevalence and seroincidence of novel influenza A infection among HIV-infected patients in Taiwan. METHODS: Between September and November 2009, before the implementation of a nationwide vaccination for novel influenza A in Taiwan, 931 HIV-infected patients and 566 persons seeking voluntary counseling and testing (VCT) for HIV infection at our university hospital were enrolled in this study. Antibody responses to novel influenza A were determined using a hemagglutination-inhibition (HI) assay. RESULTS: HIV-infected patients had a significantly lower seroprevalence of novel influenza A infection than VCT clients (14.7% vs. 33.9%, p < 0.001). The seroincidence of novel influenza A infection among HIV-infected patients was 9.4% (95% confidence interval [CI]: 7.6-11.4). On the multivariate analysis, heterosexual (odds ratio [OR]: 1.89; 95% CI: 1.105-3.227) and baseline HI titer (OR: 1.02; 95% CI: 1.001-1.038) were significantly associated with seroconversion to novel influenza A virus. CONCLUSION: HIV-infected patients demonstrated a lower seroprevalence of novel influenza A infection than HIV-uninfected patients in Taiwan in the HAART era. Among HIV-infected patients, seroconversion to novel influenza A virus, which was infrequent during the 2009 influenza epidemic, was associated with heterosexual behavior and baseline HI titer Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 579505 Therapeutic vaccines 50 Therapeutic vaccines Single DermaVir Immunization: Dose-Dependent Expansion of Precursor/Memory T Cells Against All HIV Antigens in HIV-1 Infected Individuals LISZIEWICZ J, Bakare N, Calarota SA, Banhegyi D, Szlavik J, Ujhelyi E, Toke ER, Molnar L, Lisziewicz Z, Autran B, and Lori F PLoS One ,7 (5), e35416 ,2012 AD - Genetic Immunity, Budapest, Hungary and Genetic Immunity Inc, Mclean, Virginia, United States of America eng PT - Journal Article BACKGROUND: The GIHU004 study was designed to evaluate the safety and immunogenicity of three doses of DermaVir immunization in HIV-infected subjects on fully suppressive combination antiretroviral therapy (cART). METHODOLOGY/PRINCIPAL FINDINGS: This first-in-human dose escalation study was conducted with three topical DermaVir doses targeted to epidermal Langerhans -------------------------------------------------------------------------------------------------------------- 33 / 57 EUROPRISE SCIENCE UPDATE 12-21 cells to express fifteen HIV antigens in draining lymph nodes: 0.1 mg DNA targeted to two, 0.4 mg and 0.8 mg DNA targeted to four lymph nodes. Particularly, in the medium dose cohort 0.1 mg DNA was targeted per draining lymph node via approximately 8 million Langerhans cells located in 80 cm(2) epidermis area. The 28-days study with 48-week safety follow-up evaluated HIV-specific T cell responses against Gag p17, Gag p24 and Gag p15, Tat and Rev antigens. DermaVir-associated side effects were mild, transient and not dose-dependent. Boosting of HIV-specific effector CD4(+) and CD8(+) T cells expressing IFN-gamma and IL-2 was detected against several antigens in every subject of the medium dose cohort. The striking result was the dose-dependent expansion of HIV-specific precursor/memory T cells with high proliferation capacity. In low, medium and high dose cohorts this HIV-specific T cell population increased by 325-, 136,202 and 50,759 counts after 4 weeks, and by 3,899, 9,878 and 18,382 counts after one year, respectively, compared to baseline. CONCLUSIONS/SIGNIFICANCE: Single immunization with the DermaVir candidate therapeutic vaccine was safe and immunogenic in HIV-infected individuals. Based on the potent induction of Gag, Tat and Rev-specific memory T cells, especially in the medium dose cohort, we speculate that DermaVir boost T cell responses specific to all the 15 HIV antigens expressed from the single DNA. For durable immune reactivity repeated DermaVir immunization might be required since the frequency of DermaVir-boosted HIV-specific memory T cells decreased during the 48-week follow up. TRIAL REGISTRATION: ClinicalTrial.gov NCT00712530 Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 590502 Therapy, ART 51 Therapy, ART The Elvitegravir Quad Pill: the First Once-Daily Dual-Target Anti-HIV Tablet MARCHAND C Expert Opin Investig Drugs ,2012 AD - National Cancer Institute, National Institutes of Health, Center for Cancer Research, Laboratory of Molecular Pharmacology , Bethesda, MD, 20892 , USA +1 301 435 2463 ; marchand@nihgov ENG PT - JOURNAL ARTICLE Anti-HIV combination therapies in a single formulation currently target only HIV-1 reverse transcriptase via two different mechanisms of action by associating a nucleoside and a non-nucleoside reverse transcriptase inhibitor. These combination therapies are therefore referred to as multi-class combination products. The elvitegravir Quad pill (Gilead Sciences), when approved by the Food and Drug Administration for the treatment of HIV/AIDS, will become the first once-daily dual-target antiHIV tablet. This "4 in 1" tablet targets HIV-1 integrase by elvitegravir boosted by the pharmacoenhancer cobicistat and HIV-1 reverse transcriptase by the two nucleoside reverse transcriptase inhibitors emtricitabine + tenofovir disoproxil fumarate. A second pill referred to as the 572-Trii pill (Shionogi-ViiV Healthcare, LLC), also based on the dual inhibition of integrase and reverse transcriptase, is currently in late-phase clinical trials. The availability of these novel once-daily antiHIV tablets will improve treatment adherence and offer new perspective for patient failing existing antiviral regimens Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 571404 ------------------------------------------------------ -------------------------------------------------------------------------------------------------------------- 34 / 57 EUROPRISE SCIENCE UPDATE 12-21 52 Therapy, ART Are There Benefits to Starting Antiretroviral Therapy During Primary HIV Infection? Conclusions From the Seattle Primary Infection Cohort Vary by Control Group STEKLER JD, Wellman R, Holte S, Maenza J, Stevens CE, Corey L, and Collier AC Int J STD AIDS ,23 (3), 201-206 ,2012 AD Department of Medicine eng PT - Journal Article It is controversial whether starting combination antiretroviral therapy (cART) during primary HIV infection (PHI) is beneficial. Subjects in this observational cohort began cART <30 days (group 1: acute treatment, n = 40), 31-180 days (group 2: early treatment, n = 82) or >180 days (group 3: delayed treatment, n = 35) after HIV infection, and were compared with 27 historical and 60 contemporary controls. Time to HIV-related diagnoses did not differ for group 1 (adjusted hazard ratio [aHR] 1.44, P = 0.3) or group 2 (aHR 1.17, P = 0.5) compared with contemporary controls, but it was delayed for both treated groups (aHR 0.38 for group 1, P = 0.01; and aHR 0.28 for group 2, P < 0.0001) compared with historical controls. Although rates of HIV-related diagnoses were similar in acutely treated subjects and contemporary controls, results were confounded by associations between higher CD4 counts, lower HIV RNA levels and delayed disease progression as reasons for deferring treatment. Randomized trials are needed to address benefits of cART during PHI Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 581875 Therapy, cell 53 Therapy, cell CD34-Derived Dendritic Cells Transfected Ex Vivo With HIV-Gag MRNA Induce Polyfunctional T-Cell Responses in Nonhuman Primates ROMAIN G, van Gulck E, Epaulard O, Oh S, Li D, Zurawski G, Zurawski S, Cosma A, Adam L, Chapon C, Todorova B, Banchereau J, Dereuddre-Bosquet N, Vanham G, Le Grand R, and Martinon F Eur J Immunol ,2012 AD - CEA, Division of Immuno-Virology, Institute for Emerging Diseases and Innovative Therapies (iMETI), DSV, Fontenay-aux-Roses, France; Universite Paris-Sud, UMR E1, Orsay, France ENG PT - JOURNAL ARTICLE The pivotal role of DCs in initiating the immune responses led to their use as vaccine vectors. However, the relationship between DC subsets involved in antigen presentation and the type of elicited immune responses underlined the need for the characterization of the DCs generated in vitro. The phenotypes of tissue-derived APCs from a cynomolgus macaque model for human vaccine development were compared with ex vivo-derived DCs. Monocyte/macrophages predominated in bone marrow (BM) and blood. Myeloid DCs (mDCs) were present in all tested tissues and were more highly represented than plasmacytoid DCs (pDCs). As in human skin, Langerhans cells (LCs) resided exclusively in the macaque epidermis, expressing CD11c, high levels of CD1a and Langerin (CD207). Most DC subsets were endowed with tissue-specific combinations of PRRs. DCs generated from CD34(+) BM cells (CD34-DCs) were heterogeneous in phenotype. CD34-DCs shared properties (differentiation and PRR) of dermal and epidermal DCs. After injection into macaques, CD34-DCs expressing HIV-Gag induced Gag-specific CD4(+) and CD8(+) T cells producing IFN-gamma, TNF-alpha, MIP-1beta or IL-2. In high responding animals, the numbers of polyfunctional CD8(+) T cells increased with the number of -------------------------------------------------------------------------------------------------------------- 35 / 57 EUROPRISE SCIENCE UPDATE 12-21 booster injections. This DC-based vaccine strategy elicited immune responses relevant to the DC subsets generated in vitro Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 585548 Vaccines 54 Vaccines Use of Conjoint Analysis to Assess HIV Vaccine Acceptability: Feasibility of an Innovation in the Assessment of Consumer HealthCare Preferences LEE SJ, Newman PA, Comulada WS, Cunningham WE, and Duan N Int J STD AIDS ,23 (4), 235-241 ,2012 AD - University of California Los Angeles, Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, Center for Community Health, Los Angeles, CA, USA eng PT - Journal Article Engaging consumers in prospectively shaping strategies for dissemination of health-care innovations may help to ensure acceptability. We examined the feasibility of using conjoint analysis to assess future HIV vaccine acceptability among three diverse communities: a multiethnic sample in Los Angeles, CA, USA (n = 143); a Thai resident sample in Los Angeles (three groups; n = 27) and an Aboriginal peoples sample in Toronto (n = 13). Efficacy had the greatest impact on acceptability for all three groups, followed by cross-clade protection, side-effects and duration of protection in the Los Angeles sample; side-effects and duration of protection in the Thai-Los Angeles sample; and number of doses and duration of protection in the Aboriginal peoples-Toronto sample. Conjoint analysis provided insights into universal and population-specific preferences among diverse end users of future HIV vaccines, with implications for evidence-informed targeting of dissemination efforts to optimize vaccine uptake Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 581945 Vaccines, research 55 Vaccines, research Macaque Studies of Vaccine and Microbicide Combinations for Preventing HIV-1 Sexual Transmission BAROUCH DH, Klasse PJ, Dufour J, Veazey RS, and Moore JP Proc Natl Acad Sci U S A ,2012 AD Beth Israel Deaconess Medical Center, Boston, MA 02115 ENG PT - JOURNAL ARTICLE Vaccination and the application of a vaginal microbicide have traditionally been considered independent methods to prevent the sexual transmission of HIV-1 to women. Both techniques can be effective in macaque models, and limited efficacy has been observed in clinical trials for each. Here, we have addressed whether vaccines and microbicides can be used together to provide reinforced protection against virus challenge of rhesus macaques. In two separate experiments, four groups of animals were vaccinated with a T-cell-based adenovirus (Ad) vectored vaccine aimed at reducing postinfection viral -------------------------------------------------------------------------------------------------------------- 36 / 57 EUROPRISE SCIENCE UPDATE 12-21 loads and/or a partially effective dose of a vaginal microbicide aimed at blocking infection of a highdose vaginal challenge with SIVmac251 or SHIV-162P3. In the first study, the only two protected animals were in the group that received Ad26/Ad5HVR48 vaccine vectors combined with the fusion inhibitor T-1249 as the vaginal microbicide before SIVmac251 challenge. In the second study, vaccination with Ad35/Ad26 vectors combined with the CCR5 inhibitor maraviroc as the vaginal microbicide led to significant reductions of both acquisition of infection and postinfection viral loads following SHIV-SF162P3 challenge. As expected, the vaccine by itself reduced viral loads but had no acquisition effect, whereas the microbicide had a partial acquisition effect but minimal impact on viral loads. For both measures of protective efficacy, the vaccine-microbicide combination differed more from controls than did either separate intervention. Overall, the data suggest that vaccines and microbicides are complementary techniques that may protect better when used together than separately Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 586094 -----------------------------------------------------56 Vaccines, research Improved Outlook on HIV-1 Prevention and Vaccine Development VASAN S and Michael NL Expert Opin Biol Ther ,2012 AD - US Military HIV Research Program (MHRP), Armed Forces Research Institute of Medical Sciences (AFRIMS) , Bangkok , Thailand +1 301 500 3601 ; nmichael@hivresearchorg ENG PT - JOURNAL ARTICLE Introduction: The development of an effective vaccine against HIV-1 has been challenging but recent advances in both the HIV prevention landscape and the partial efficacy of the recent RV144 vaccine efficacy trial in Thailand provide hope for an improved arsenal of approaches to prevent HIV-1 transmission. Areas covered: This review describes recent advances in HIV-1 prevention such as circumcision, microbicides and pre-exposure prophylaxis with antiretroviral therapy, but focuses mainly on the current state of HIV-1 vaccine development in the post-RV144 era. Expert opinion: The field of HIV-1 vaccine development has been plagued by the unprecedented challenges involved with designing a vaccine effective in preventing transmission of a retrovirus, due in part to sequence diversity, retroviral integration into host chromosomes, establishment of reservoir sites and glycosylation shielding of the HIV-1 envelope. The partial efficacy of the recent RV144 vaccine trial in Thailand may allow for better understanding of immune correlates of infection risk, which could enable iterative improvements to vaccine regimens in the development pipeline. In parallel, a number of promising vaccine strategies incorporating viral vectors, novel immunogens, delivery systems and adjuvants are advancing in clinical development. Vaccine development must occur in parallel with continued advances in HIV-1 prevention Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 583109 -----------------------------------------------------57 Vaccines, research International Network for Comparison of HIV Neutralization Assays: The NeutNet Report II HEYNDRICKX L, Heath A, Sheik-Khalil E, Alcami J, Bongertz V, Jansson M, Malnati M, Montefiori D, Moog C, Morris L, Osmanov S, Polonis V, Ramaswamy M, Sattentau Q, Tolazzi M, Schuitemaker H, Willems B, Wrin T, Fenyo EM, and Scarlatti G -------------------------------------------------------------------------------------------------------------- 37 / 57 EUROPRISE SCIENCE UPDATE 12-21 PLoS One ,7 (5), e36438 ,2012 AD - Virology Unit, Biomedical Department, Institute of Tropical Medicine, Antwerp, Belgium eng PT - Journal Article BACKGROUND: Neutralizing antibodies provide markers for vaccine-induced protective immunity in many viral infections. By analogy, HIV-1 neutralizing antibodies induced by immunization may well predict vaccine effectiveness. Assessment of neutralizing antibodies is therefore of primary importance, but is hampered by the fact that we do not know which assay(s) can provide measures of protective immunity. An international collaboration (NeutNet) involving 18 different laboratories previously compared different assays using monoclonal antibodies (mAbs) and soluble CD4 (Phase I study). METHODS: In the present study (Phase II), polyclonal reagents were evaluated by 13 laboratories. Each laboratory evaluated nine plasmas against an 8 virus panel representing different genetic subtypes and phenotypes. TriMab, a mixture of three mAbs, was used as a positive control allowing comparison of the results with Phase I in a total of nine different assays. The assays used either uncloned virus produced in peripheral blood mononuclear cells (PBMCs) (Virus Infectivity Assays, VIA), or Env (gp160)-pseudotyped viruses (pseudoviruses, PSV) produced in HEK293T cells from molecular clones or from uncloned virus. Target cells included PBMC and genetically engineered cell lines in either single- or multiple-cycle infection format. Infection was quantified by using a range of assay read-outs including extra- or intra-cellular p24 antigen detection, luciferase, betagalactosidase or green fluorescent protein (GFP) reporter gene expression. FINDINGS: Using TriMab, results of Phase I and Phase II were generally in agreement for six of the eight viruses tested and confirmed that the PSV assay is more sensitive than PBMC (p = 0.014). Comparisons with the polyclonal reagents showed that sensitivities were dependent on both virus and plasma. CONCLUSIONS: Here we further demonstrate clear differences in assay sensitivities that were dependent on both the neutralizing reagent and the virus. Consistent with the Phase I study, we recommend parallel use of PSV and VIA for vaccine evaluation Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 590544 -----------------------------------------------------58 Vaccines, research PD-1/PD-L1 Blockade Can Enhance HIV-1 Gag-Specific T Cell Immunity Elicited by Dendritic Cell-Directed Lentiviral Vaccines DAI B, Xiao L, Bryson PD, Fang J, and Wang P Mol Ther ,2012 AD - Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California, USA ENG PT - JOURNAL ARTICLE Exhaustion of CD8(+) T cells and upregulation of programmed death 1 (PD-1), a negative regulator of T cell activation, are characteristic features of individuals chronically infected with human immunodeficiency virus type 1. In a previous study, we showed in mice that a dendritic cell-directed lentiviral vector (DCLV) system encoding the human immunodeficiency virus (HIV)-1 Gag protein was an efficient vaccine modality to induce a durable Gag-specific T cell immune response. In this study, we demonstrate that blocking of the PD-1/PD-1 ligand (PD-L) inhibitory signal via an anti-PD-L1 antibody generated an enhanced HIV-1 Gag-specific CD8(+) immune response following both a single round of DCLV immunization and a homologous prime/boost regimen. The prime/boost regimen combined with PD-L1 blockade generated very high levels of Gag-specific CD8(+) T cells comprising several valuable features: improved ability to produce multiple cytokines, responding to a broader range of Gag-derived epitopes, and long-lasting memory. This enhanced cellular immune response generated by DCLV immunization combined with anti-PD-L1 blockade correlated with improved viral control following challenge with Gag-expressing vaccinia virus. Taken together, our studies offer -------------------------------------------------------------------------------------------------------------- 38 / 57 EUROPRISE SCIENCE UPDATE 12-21 evidence to support the use of PD-1/PD-L1 blockade as an adjuvant modality to enhance antigenspecific immune responses elicited by T cell-based immunizations such as DCLV Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 588271 -----------------------------------------------------59 Vaccines, research Accelerated Heterologous Adenovirus Prime-Boost SIV Vaccine in Neonatal Rhesus Monkeys LIU J, Li H, Iampietro MJ, and Barouch DH J Virol ,2012 AD - Division of Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215 ENG PT - JOURNAL ARTICLE A pediatric HIV-1 vaccine would be desirable to protect infants against HIV-1 transmission from breastfeeding. Such a vaccine would need to induce protective immunity at mucosal surfaces in neonates as soon as possible after birth. Recombinant adenovirus (rAd) vectors have been shown to elicit potent systemic and mucosal virus-specific immune responses in adult non-human primates and humans, but these vectors have not previously been comprehensively studied in infants. In this study, we demonstrate that a single injection of rAd26 encoding SIVmac239 Gag on the day of birth elicited detectable Gag-specific cellular immune responses in rhesus monkeys, but these responses were transient and waned quickly. In contrast, an accelerated heterologous prime-boost regimen involving administration of rAd35 at birth and rAd26 at 4 weeks of life elicited potent and durable Gag-specific cellular and humoral immune responses in neonatal rhesus monkeys, including mucosal responses that remained detectable at one year of age. These results suggest the potential of an accelerated heterologous rAd prime-boost regimen as a candidate HIV-1 vaccine for newborns Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 593160 -----------------------------------------------------60 Vaccines, research Gene-Based Vaccination With a Mis-Matched Envelope Protects Against Simian Immunodeficiency Virus Infection in Non-Human Primates FLATZ L, Cheng C, Wang L, Foulds K, Ko SY, Kong WP, Roychoudhuri R, Shi W, Bao S, Todd JP, Asmal M, Shen L, Donaldson M, Schmidt SD, Gall J, Pinschewer DD, Letvin NL, Rao S, Mascola JR, Roederer M, and Nabel GJ J Virol ,2012 AD - Vaccine Research Center, NIAID, National Institutes of Health, Bldg 40, Room 4502, MSC-3005, 40 Convent Drive, Bethesda, MD 20892-3005 ENG PT - JOURNAL ARTICLE The RV144 trial demonstrated that an experimental AIDS vaccine can prevent human immunodeficiency virus-1 (HIV-1) infection in humans. Because of its limited efficacy, further understanding of the mechanism of preventive AIDS vaccines remains a priority, and non-human primate models of lentiviral infection provide an opportunity to define immunogens, vectors, and correlates of immunity. In this study, we show that prime-boost vaccination with a mis-matched HIV-1 Envelope (env) gene, derived from SIVmac239, prevents infection by the SIVsmE660 virus intra-rectally. -------------------------------------------------------------------------------------------------------------- 39 / 57 EUROPRISE SCIENCE UPDATE 12-21 Analysis of different gene-based prime-boost immunization regimens revealed that recombinant adenovirus 5 (rAd5) prime followed by replication-defective lymphocytic choriomeningitis virus (rLCMV) boost elicited robust CD4 and CD8 T-cell and humoral immune responses. This vaccine protected against infection after repetitive mucosal challenge with an efficacy of 82% per exposure and 62% cumulatively. No effect was seen on viremia in infected vaccinated monkeys compared to controls. Protection correlated with the presence of neutralizing antibodies to the challenge viruses tested in peripheral blood mononuclear cells. These data indicate that a vaccine expressing a mismatched Env gene alone can prevent SIV infection in NHP and identifies an immune correlate that may guide immunogen selection and immune monitoring for clinical efficacy trials Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 593152 -----------------------------------------------------61 Vaccines, research Association of Enhanced HIV-1 Neutralization by a Single Y681H Substitution in Gp41 With Increased Gp120-CD4 Interaction and Macrophage Infectivity RINGE R and Bhattacharya J PLoS One ,7 (5), e37157 ,2012 AD - Department of Molecular Virology, National AIDS Research Institute, Indian Council of Medical Research, Bhosari, Pune, India ENG PT - JOURNAL ARTICLE HIV-1 variants that show unusual sensitivity to autologous antibodies due to presence of critical neutralization signatures would likely contribute towards rational envelope based HIV-1 vaccine design. In the present study, we found that presence of a naturally occurring H681 in gp41 membrane proximal external region (MPER) of a clade C envelope (Env) obtained from a recently infected Indian patient conferred increased sensitivity to autologous and heterologous plasma antibodies. Furthermore, Env-pseudotyped viruses expressing H681 showed increased sensitivity to soluble CD4, b12 and 4E10 monoclonal antibodies both in related and unrelated Envs and was corroborated with increased Env susceptibility and binding to cellular CD4 as well as with prolonged exposure of MPER epitopes. The increased gp120-CD4 interaction was further associated with relative exposure of CD4induced epitopes and macrophage infectivity. In summary, our data indicate that Y681H substitution exposes neutralizing epitopes in CD4bs and MPER towards comprehensive interference in HIV-1 entry Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 606344 -----------------------------------------------------62 Vaccines, research HIV Vaccine Design: the Neutralizing Antibody Conundrum STAMATATOS L Curr Opin Immunol ,2012 AD - Seattle BioMed and the University of Washington, Seattle, WA, United States ENG PT JOURNAL ARTICLELink : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 595693 -------------------------------------------------------------------------------------------------------------- 40 / 57 EUROPRISE SCIENCE UPDATE 12-21 ------------------------------------------------------ Virology 63 Virology Co-Evolution of Primate SAMHD1 and Lentivirus Vpx Leads to the Loss of the Vpx Gene in HIV-1 Ancestor ZHANG C, de Silva S, Wang JH, and Wu L PLoS One ,7 (5), e37477 ,2012 AD Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu, China eng PT - Journal Article Cross-species transmission and adaptation of simian immunodeficiency viruses (SIVs) to humans have given rise to human immunodeficiency viruses (HIVs). HIV type 1 (HIV-1) and type 2 (HIV-2) were derived from SIVs that infected chimpanzee (SIVcpz) and sooty mangabey (SIVsm), respectively. The HIV-1 restriction factor SAMHD1 inhibits HIV-1 infection in human myeloid cells and can be counteracted by the Vpx protein of HIV-2 and the SIVsm lineage. However, HIV-1 and its ancestor SIVcpz do not encode a Vpx protein and HIV-1 has not evolved a mechanism to overcome SAMHD1mediated restriction. Here we show that the co-evolution of primate SAMHD1 and lentivirus Vpx leads to the loss of the vpx gene in SIVcpz and HIV-1. We found evidence for positive selection of SAMHD1 in orangutan, gibbon, rhesus macaque, and marmoset, but not in human, chimpanzee and gorilla that are natural hosts of Vpx-negative HIV-1, SIVcpz and SIVgor, respectively, indicating that vpx drives the evolution of primate SAMHD1. Ancestral host state reconstruction and temporal dynamic analyses suggest that the most recent common ancestor of SIVrcm, SIVmnd, SIVcpz, SIVgor and HIV-1 was a SIV that had a vpx gene; however, the vpx gene of SIVcpz was lost approximately 3643 to 2969 years ago during the infection of chimpanzees. Thus, HIV-1 could not inherit the lost vpx gene from its ancestor SIVcpz. The lack of Vpx in HIV-1 results in restricted infection in myeloid cells that are important for antiviral immunity, which could contribute to the AIDS pandemic by escaping the immune responses Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 574228 -----------------------------------------------------64 Virology Refined Identification of Neutralization-Resistant HIV-1 CRF02_AG Viruses JACOB RA, Abrahams F, Tongo M, Schomaker M, Roux P, Mpoudi Ngole E, Burgers WA, and Dorfman JR J Virol ,2012 AD - International Centre for Genetic Engineering and Biotechnology, Cape Town ENG PT - JOURNAL ARTICLE We studied neutralization of CRF02_AG HIV-1-infected plasma samples. In contrast to previous reports, these samples neutralized CRF02_AG viruses better than other viruses. This included six of eight CRF02_AG viruses previously designated as resistant (tier 2/3 or 3). Only 253-11 and 278-50 remained highly resistant, but were sensitive to membrane proximal external region (MPER)-specific monoclonal antibodies, suggesting neutralization targets for even these viruses. We propose testing viruses with neutralizing within-subtype samples for evaluating neutralization resistance Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 573859 -------------------------------------------------------------------------------------------------------------- 41 / 57 EUROPRISE SCIENCE UPDATE 12-21 -----------------------------------------------------65 Virology [Study on the Molecular-Epidemiological Characteristics of HIV-1 in Shenzhen, 1992-2008] ZHAO GL, Yu W, Zhang JJ, Chen L, Feng TJ, Wang F, Hong FC, Wang XH, and Li Q Zhonghua Liu Xing Bing Xue Za Zhi ,33 (1), 82-87 ,2012 AD Shenzhen Center for Chronic Disease Control, Shenzhen 518020, China chi PT English Abstract PT - Journal Article OBJECTIVE: To investigate the epidemiological characteristics of HIV-1 subtype in Shenzhen from 1992 to 2008. METHODS: 489 HIV-1 positive plasma samples were collected from 1992 to 2008 in Shenzhen.HIV-1 env genes were amplified by nested-PCR from RNA. Phylogenetic analysis was performed on data regarding the nucleotide sequence. RESULTS: A total of 464 sequences were amplified and genotyped. Data from this study revealed that CRF01_AE was a predominant HIV-1 subtype in Shenzhen (64.4%, 299/464), followed by subtypes CRF_BC (17.5%, 81/464), B' (14.7%, 68/464) and B (2.4%, 11/464). Subtype C (0.4%, 2/464), A1 (0.2%, 1/464), CRF02_AG (0.2%, 1/464) and CRF06_cpx (0.2%, 1/464) were also prevalent in Shenzhen. CRF01_AE and CRF_BC were predominant among heterosexuals, homosexuals and injection drug users, while B' was predominant among blood donors. Results from phylogenetic tree analysis showed that some of the HIV-1 clusters had been defined in CRF01_AE strains at different time or groups with different transmission routes. Cross-infections were also seen. CONCLUSION: CRF01_AE was the predominant HIV-1 subtype in Shenzhen while CRF_BC, B, B', C, A1, CRF02_AG and a small amount of CRF06_cpx or recombinant subtypes were prevalent in this city. Different subtypes showed great variation in the process of epidemics Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 575118 -----------------------------------------------------66 Virology HIV-2 Infection in Providence, Rhode Island From 2002 to 2011 HOLLENBECK B and Beckwith C HIV Med ,2012 AD - Department of Medicine, Alpert Medical School of Brown University, Providence, RI, USA ENG PT - JOURNAL ARTICLE OBJECTIVES: In contrast to HIV-1 infection, little is known about the natural disease course of HIV-2 and its response to antiretrovirals (ARVs). We describe a cohort of HIV-2-infected patients, focusing on the method of diagnosis, ARV treatment and complications. METHODS: Through a retrospective review of medical records at our centre, we identified 12 patients with HIV-2 infection in our clinic population (1400 active patients) who received care between 2002 and 2011. We summarized clinical characteristics, ARV treatment and outcomes. RESULTS: Seven of the patients were male and five were female. All patients were born in West African countries. The mode of transmission was heterosexual intercourse in 11 patients, and injecting drug use in one patient. The median CD4 count at the time of diagnosis was 668 cells/muL (range 23 to 1546 cells/muL). HIV-2 quantitative viral load measurements were not uniformly available to clinicians. Four patients were treated with protease inhibitor-based regimens, with a mean increase in CD4 count of 183 cells/muL (range 43 to 341 cells/muL). The other eight patients have been observed off ARVs. Two patients experienced complications from HIV, one patient had HIV encephalopathy and molluscom contagiosum, and another had microsporidiosis infection in the setting of AIDS. CONCLUSION: Our results support those -------------------------------------------------------------------------------------------------------------- 42 / 57 EUROPRISE SCIENCE UPDATE 12-21 of previous studies indicating that HIV-2 has a more indolent disease course than HIV-1, with a spectrum of disease ranging from asymptomatic to AIDS. Development of a reliable quantitative HIV-2 viral load assay to guide management is needed. Further research studies are needed to establish the best time to start ARV treatment in HIV-2-infected patients Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 574645 -----------------------------------------------------67 Virology Characterization of HIV-1 Subtypes and Drug Resistance Mutations Among Individuals Infected With HIV in Georgia DVALI N, Parker MM, Chkhartishvili N, Sharvadze L, Gochitashvili N, Abutidze A, Karchava M, Dehovitz JA, and Tsertsvadze T J Med Virol ,84 (7), 1002-1008 ,2012 AD - Infectious Diseases, AIDS and Clinical Immunology Research Center, Tbilisi, Georgia natia_dvali@yahoocom eng PT - Journal Article In order to describe HIV-1 subtypes and drug resistance mutations in Georgia, blood samples from 153 patients infected with HIV-1 collected from 2006 to 2008 were genotyped. Of these, 126 samples were from newly diagnosed, antiretroviral (ARV)-naive patients and 27 from ARV-treated patients. Partial pol region sequences were used to identify drug resistance mutations and to conduct phylogenetic analysis for subtype determination. The results indicated that 138 (90.2%) patients harbored subtype A viruses, 11 (7.2%) carried subtype B virus, two subtype G (1.3%), one (0.6%) subtype F and one (0.6%) 03_AB recombinant. All subtype A strains clustered with the Former Soviet Union A (A FSU) subtype. Among patients with no prior exposure to ARVs, mutations associated with resistance were detected in five patients: three (2.4%) patients had reverse transcriptase (RT) inhibitor mutations and two other patients had the protease (PI) inhibitor associated mutation M46I. PI mutation V77I was found in 42 of subtype A isolates. Of 27 ARV-treated patients, 22 (81.5%) harbored at least one nucleoside reverse transcriptase inhibitors (NRTI), a non-NRTI (NNRTI) and/or a PI mutation. The most common NRTI resistance mutation was M184V/I (74.1%). Frequency of thymidine analog mutations was relatively low (25.9%). With regard to NNRTI mutations, G190S/A was the most frequent mutation, which might be a preferred mutations for subtype A. Georgia's HIV epidemic continues to be dominated by Subtype A FSU. The prevalence of transmitted drug resistance is low, but has the potential to increase with increasing use of ARVs. J. Med. Virol. 84: 1002-1008, 2012. (c) 2012 Wiley Periodicals, Inc Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 585715 -----------------------------------------------------68 Virology Meeting the Challenge of HIV Diversity: Strategies to Mitigate the Impact of HIV-1 Genetic Heterogeneity on Performance of Nucleic Acid Testing Assays HACKETT J JR Clin Lab ,58 (3-4), 199-202 ,2012 AD - Emerging Pathogens and Virus Discovery Program, Abbott Diagnostics, Abbott Park, IL 60064-3500, USA johnhackett@abbottcom -------------------------------------------------------------------------------------------------------------- 43 / 57 EUROPRISE SCIENCE UPDATE 12-21 eng PT Journal ArticleLink : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 582491 -----------------------------------------------------69 Virology Feline Immunodeficiency Virus in South America TEIXEIRA BM, Hagiwara MK, Cruz JC, and Hosie MJ Viruses ,4 (3), 383-396 ,2012 AD - Department of Pathology and Center for Biodefense and Emerging Infectious Diseases, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0609, USA eng PT - Journal Article The rapid emergence of AIDS in humans during the period between 1980 and 2000 has led to extensive efforts to understand more fully similar etiologic agents of chronic and progressive acquired immunodeficiency disease in several mammalian species. Lentiviruses that have gene sequence homology with human immunodeficiency virus (HIV) have been found in different species (including sheep, goats, horses, cattle, cats, and several Old World monkey species). Lentiviruses, comprising a genus of the Retroviridae family, cause persistent infection that can lead to varying degrees of morbidity and mortality depending on the virus and the host species involved. Feline immunodeficiency virus (FIV) causes an immune system disease in domestic cats (Felis catus) involving depletion of the CD4+ population of T lymphocytes, increased susceptibility to opportunistic infections, and sometimes death. Viruses related to domestic cat FIV occur also in a variety of nondomestic felids. This is a brief overview of the current state of knowledge of this large and ancient group of viruses (FIVs) in South America Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 590677 -----------------------------------------------------70 Virology Viral Diversity and Diversification of Major Non-Structural Genes Vif, Vpr, Vpu, Tat Exon 1 and Rev Exon 1 During Primary HIV-1 Subtype C Infection ROSSENKHAN R, Novitsky V, Sebunya TK, Musonda R, Gashe BA, and Essex M PLoS One ,7 (5), e35491 ,2012 AD - Department of Biological Sciences, University of Botswana, Gaborone, Botswana eng PT - Journal Article To assess the level of intra-patient diversity and evolution of HIV-1C non-structural genes in primary infection, viral quasispecies obtained by single genome amplification (SGA) at multiple sampling timepoints up to 500 days post-seroconversion (p/s) were analyzed. The mean intra-patient diversity was 0.11% (95% CI; 0.02 to 0.20) for vif, 0.23% (95% CI; 0.08 to 0.38) for vpr, 0.35% (95% CI; -0.05 to 0.75) for vpu, 0.18% (95% CI; 0.01 to 0.35) for tat exon 1 and 0.30% (95% CI; 0.02 to 0.58) for rev exon 1 during the time period 0 to 90 days p/s. The intra-patient diversity increased gradually in all non-structural genes over the first year of HIV-1 infection, which was evident from the vif mean intrapatient diversity of 0.46% (95% CI; 0.28 to 0.64), vpr 0.44% (95% CI; 0.24 to 0.64), vpu 0.84% (95% CI; 0.55 to 1.13), tat exon 1 0.35% (95% CI; 0.14 to 0.56 ) and rev exon 1 0.42% (95% CI; 0.18 to 0.66) during the time period of 181 to 500 days p/s. There was a statistically significant increase in viral -------------------------------------------------------------------------------------------------------------- 44 / 57 EUROPRISE SCIENCE UPDATE 12-21 diversity for vif (p = 0.013) and vpu (p = 0.002). No associations between levels of viral diversity within the non-structural genes and HIV-1 RNA load during primary infection were found. The study details the dynamics of the non-structural viral genes during the early stages of HIV-1C infection Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 590503 -----------------------------------------------------71 Virology Two Unique Recombinant Forms Identified in Incident HIV-1 Infections in Thai Blood Donors RUTVISUTTINUNT W, Sirivichayakul S, Oota S, Assawadarachai V, Poltavee K, Savadsuk H, Pattanachaiwit S, Chaemchuen S, Arroyo MA, Paris RM, Michael NL, Kim JH, Ruxruthgam K, Phanuphak P, de Souza MS, and Tovanabutra S AIDS Res Hum Retroviruses ,2012 AD - Armed Forces Research Institute of Medical Sciences, Department of Retrovirology, Bangkok, Thailand; wiriyar@afrimsorg ENG PT - JOURNAL ARTICLE HIV-1 genetic diversity of recently seroconverting (<12 months) Thai repeated blood donors attending the National Blood Centre, Thai Red Cross Society (NBC, TRCS) from September 2007 until March 2008 was assessed. Ten HIV-1 recent seroconvertors (10/239,134 donations) were identified during the study period. The estimated median time to seroconversion was 67.3 days (range: 45.5 - 102.0 days), and viral load ranged from 307 to 341,805 copies HIV-1 RNA/ml. MHAbce, a real-time based PCR genotyping assay, identified six CRF01_AE, two CRF01_AE/B recombinants, one subtype B and one CRF01_AE/B dual infection. Nine samples were further characterized by full genome sequencing, identifying CRF01_AE (N=6), unique CRF01_AE/B recombinants (N=2), and subtype B (N=1). One recombinant contained 13 breakpoints located in gag, pol, vif, vpr, env and nef while the other recombinant contained 10 breakpoints located in pol, vif, env and nef. This study found two unique CRF01B recombinants circulating in 10 recent HIV-1 positive subjects from a blood donor population in Thailand Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 587412 -----------------------------------------------------72 Virology New Insights into the Evolutionary Rate of HIV-1 at the Within-Host and Epidemiological Levels LYTHGOE KA and Fraser C Proc Biol Sci ,2012 AD - Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, , St Mary's Campus, London W2 1PG, UK ENG PT - JOURNAL ARTICLE Over calendar time, HIV-1 evolves considerably faster within individuals than it does at the epidemic level. This is a surprising observation since, from basic population genetic theory, we would expect the genetic substitution rate to be similar across different levels of biological organization. Three different mechanisms could potentially cause the observed mismatch in phylogenetic rates of divergence: temporal changes in selection pressure during the course of infection; frequent reversion of adaptive -------------------------------------------------------------------------------------------------------------- 45 / 57 EUROPRISE SCIENCE UPDATE 12-21 mutations after transmission; and the storage of the virus in the body followed by the preferential transmission of stored ancestral virus. We evaluate each of these mechanisms to determine whether they are likely to make a major contribution to the mismatch in phylogenetic rates. We conclude that the cycling of the virus through very long-lived memory CD4(+) T cells, a process that we call 'store and retrieve', is probably the major contributing factor to the rate mismatch. The preferential transmission of ancestral virus needs to be integrated into evolutionary models if we are to accurately predict the evolution of immune escape, drug resistance and virulence in HIV-1 at the population level. Moreover, early infection viruses should be the major target for vaccine design, because these are the viral strains primarily involved in transmission Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 593106 Virology, resistance 73 Virology, resistance Virological Response and HIV Drug Resistance 12 Months After Antiretroviral Therapy Initiation at 2 Clinics in Nigeria UGBENA R, Aberle-Grasse J, Diallo K, Bassey O, Jelpe T, Rottinghaus E, Azeez A, Akpan R, Muhammad M, Shanmugam V, Singh S, and Yang C Clin Infect Dis ,54 Suppl 4, S375-S380 ,2012 AD CDC-Nigeria, Centers for Disease Control and Prevention, Abuja eng PT - Journal Article This report describes a pilot study, conducted in Nigeria, of the World Health Organization protocol for monitoring human immunodeficiency virus (HIV) drug resistance (HIVDR) and associated program factors among patients receiving first-line antiretroviral therapy (ART). In 2008, 283 HIV-infected patients starting ART were consecutively enrolled at 2 ART clinics in Abuja. Twelve months after ART initiation, 62% were alive and on first-line ART, 3% had died, 1% had transferred out of the program, and 34% were lost to follow-up. Among patients on first-line ART at 12 months, 90% had viral suppression. However, in view of the high loss to follow-up rate (34%), strategies for patient retention and tracking are critical to minimize possible HIVDR and optimize treatment outcomes Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 544206 -----------------------------------------------------74 Virology, resistance Surveillance of HIV Drug Resistance in Children Receiving Antiretroviral Therapy: A Pilot Study of the World Health Organization's Generic Protocol in Maputo, Mozambique VAZ P, Augusto O, Bila D, Macassa E, Vubil A, Jani IV, Pillon R, Sandstrom P, Sutherland D, Giaquinto C, Jordan MR, and Bertagnolio S Clin Infect Dis ,54 Suppl 4, S369-S374 ,2012 AD - Department of Pediatrics, Hospital Dia Pediatrico, Maputo Central Hospital eng PT - Journal Article Between 2007 and 2008, the Mozambique Ministry of Health conducted an assessment of human immunodeficiency virus drug resistance (HIVDR) using World Health Organization (WHO) methods in -------------------------------------------------------------------------------------------------------------- 46 / 57 EUROPRISE SCIENCE UPDATE 12-21 a cohort of children initiating antiretroviral therapy (ART) at the main pediatric ART referral center in Mozambique. It was shown that prior to ART initiation 5.4% of children had HIVDR that was associated with nevirapine perinatal exposure (P < .001). Twelve months after ART initiation, 77% had viral load suppression (<1000 copies/mL), exceeding the WHO target of >/=70%; 10.3% had HIVDR at 12 months. Baseline HIVDR (P = .04), maternal prevention of mother-to-child transmission (P = .02), and estimated days of missed medication (P = .03) predicted HIVDR at 12 months. As efforts to eliminate pediatric AIDS are intensified, implementation of ritonavir-boosted protease inhibitor regimens in children with prevention of mother-to-child transmission exposure may reduce risk of virological failure in our setting Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 544205 -----------------------------------------------------75 Virology, resistance Prevalence of HIV Drug Resistance Before and 1 Year After Treatment Initiation in 4 Sites in the Malawi Antiretroviral Treatment Program WADONDA-KABONDO N, Bennett D, van Oosterhout JJ, Moyo K, Hosseinipour M, Devos J, Zhou Z, AberleGrasse J, Warne TR, Mtika C, Chilima B, Banda R, Pasulani O, Porter C, Phiri S, Jahn A, Kamwendo D, Jordan MR, Kabuluzi S, Chimbwandira F, Kagoli M, Matatiyo B, Demby A, and Yang C Clin Infect Dis ,54 Suppl 4, S362-S368 ,2012 AD Department of Preventive Health, Ministry of Health, Lilongwe, Malawi eng PT - Journal Article Since 2004, the Malawi antiretroviral treatment (ART) program has provided a public health-focused system based on World Health Organization clinical staging, standardized first-line ART regimens, limited laboratory monitoring, and no patient-level monitoring of human immunodeficiency virus drug resistance (HIVDR). The Malawi Ministry of Health conducts periodic evaluations of HIVDR development in prospective cohorts at sentinel clinics. We evaluated viral load suppression, HIVDR, and factors associated with HIVDR in 4 ART sites at 12-15 months after ART initiation. More than 70% of patients initiating ART had viral suppression at 12 months. HIVDR prevalence (6.1%) after 12 months of ART was low and largely associated with baseline HIVDR. Better follow-up, removal of barriers to on-time drug pickups, and adherence education for patients 16-24 years of age may further prevent HIVDR Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 544204 -----------------------------------------------------76 Virology, resistance A Retrospective Survey of HIV Drug Resistance Among Patients 1 Year After Initiation of Antiretroviral Therapy at 4 Clinics in Malawi WADONDA-KABONDO N, Hedt BL, van Oosterhout JJ, Moyo K, Limbambala E, Bello G, Chilima B, Schouten E, Harries A, Massaquoi M, Porter C, Weigel R, Hosseinipour M, Aberle-Grasse J, Jordan MR, Kabuluzi S, and Bennett DE Clin Infect Dis ,54 Suppl 4, S355-S361 ,2012 AD Ministry of Health, Lilongwe, Malawi eng PT - Journal Article -------------------------------------------------------------------------------------------------------------- 47 / 57 EUROPRISE SCIENCE UPDATE 12-21 In 2004, Malawi began scaling up its national antiretroviral therapy (ART) program. Because of limited treatment options, population-level surveillance of acquired human immunodeficiency virus drug resistance (HIVDR) is critical to ensuring long-term treatment success. The World Health Organization target for clinic-level HIVDR prevention at 12 months after ART initiation is >/=70%. In 2007, viral load and HIVDR genotyping was performed in a retrospective cohort of 596 patients at 4 ART clinics. Overall, HIVDR prevention (using viral load </=400 copies/mL) was 72% (95% confidence interval [CI], 67%-77%; range by site, 60%-83%) and detected HIVDR was 3.4% (95% CI, 1.8%-5.8%; range by site, 2.5%-4.7%). Results demonstrate virological suppression and HIVDR consistent with previous reports from sub-Saharan Africa. High rates of attrition because of loss to follow-up were noted and merit attention Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 544203 -----------------------------------------------------77 Virology, resistance Initial Virologic Response and HIV Drug Resistance Among HIVInfected Individuals Initiating First-Line Antiretroviral Therapy at 2 Clinics in Chennai and Mumbai, India HINGANKAR NK, Thorat SR, Deshpande A, Rajasekaran S, Chandrasekar C, Kumar S, Srikantiah P, Chaturbhuj DN, Datkar SR, Deshmukh PS, Kulkarni SS, Sane S, Reddy DC, Garg R, Jordan MR, Kabra S, Tripathy SP, and Paranjape RS Clin Infect Dis ,54 Suppl 4, S348-S354 ,2012 AD National AIDS Research Institute, Pune eng PT - Journal Article Human immunodeficiency virus drug resistance (HIVDR) in cohorts of patients initiating antiretroviral therapy (ART) at clinics in Chennai and Mumbai, India, was assessed following World Health Organization (WHO) guidelines. Twelve months after ART initiation, 75% and 64.6% of participants at the Chennai and Mumbai clinics, respectively, achieved viral load suppression of <1000 copies/mL (HIVDR prevention). HIVDR at initiation of ART (P <.05) and 12-month CD4 cell counts <200 cells/muL (P <.05) were associated with HIVDR at 12 months. HIVDR prevention exceeded WHO guidelines (>/=70%) at the Chennai clinic but was below the target in Mumbai due to high rates of loss to follow-up. Findings highlight the need for defaulter tracing and scale-up of routine viral load testing to identify patients failing first-line ART Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 544202 -----------------------------------------------------78 Virology, resistance Surveillance of Transmitted HIV Drug Resistance Using Matched Plasma and Dried Blood Spot Specimens From Voluntary Counseling and Testing Sites in Ho Chi Minh City, Vietnam, 20072008 DUC NB, Hien BT, Wagar N, Tram TH, Giang le T, Yang C, Wolfe MI, Hien NT, and Tuan NA Clin Infect Dis ,54 Suppl 4, S343-S347 ,2012 -------------------------------------------------------------------------------------------------------------- 48 / 57 EUROPRISE SCIENCE UPDATE 12-21 AD - Department of Health and Human Services/US Centers for Disease Control and Prevention eng PT - Journal Article During 2007-2008, surveillance of transmitted human immunodeficiency virus (HIV) drug resistance (TDR) was performed following World Health Organization guidance among clients with newly diagnosed HIV infection attending voluntary counseling and testing (VCT) sites in Ho Chi Minh City (HCMC), Vietnam. Moderate (5%-15%) TDR to nonnucleoside reverse-transcriptase inhibitors (NNRTIs) was observed among VCT clients aged 18-21 years. Follow-up surveillance of TDR in HCMC and other geographic regions of Vietnam is warranted. Data generated will guide the national HIV drug resistance surveillance strategy and support selection of current and future first-line antiretroviral therapy and HIV prevention programs Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 544201 -----------------------------------------------------79 Virology, resistance Transmitted Antiretroviral Drug Resistance Among Drug-Naive Female Sex Workers With Recent Infection in Kampala, Uganda SSEMWANGA D, Ndembi N, Lyagoba F, Magambo B, Kapaata A, Bukenya J, Lubega GW, Bertagnolio S, Vandepitte J, Grosskurth H, and Kaleebu P Clin Infect Dis ,54 Suppl 4, S339-S342 ,2012 AD MRC/UVRI Uganda Research Unit on AIDS, Entebbe eng PT - Journal Article During 2006-2007, transmitted human immunodeficiency virus (HIV) drug resistance (TDR) among drugnaive women with newly diagnosed HIV infection and likely to be recently infected when attending antenatal clinics in Entebbe was found to be <5% with use of the World Health Organization (WHO) survey method. Using the same method, we attempted to classify TDR among women who seroconverted during 2008-2010 and who were identified from a cohort of recently infected sex workers in Kampala, Uganda. TDR mutations were identified using the 2009 WHO TDR mutations list. The WHO survey method could not be used to classify TDR because the necessary sample size was not reached during the survey period. However, a point prevalence estimate of 2.6% (95% confidence interval, 0.07%-13.8%) nonnucleoside reverse-transcriptase inhibitor TDR was determined Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 544200 -----------------------------------------------------80 Virology, resistance Surveillance of Transmitted HIV-1 Drug Resistance in Gauteng and KwaZulu-Natal Provinces, South Africa, 2005-2009 HUNT GM, Ledwaba J, Basson AE, Moyes J, Cohen C, Singh B, Bertagnolio S, Jordan MR, Puren A, and Morris L Clin Infect Dis ,54 Suppl 4, S334-S338 ,2012 AD National Institute for Communicable Diseases, Johannesburg, South Africa eng PT - Journal Article Surveillance of human immunodeficiency virus type 1 transmitted drug resistance (TDR) was conducted among pregnant women in South Africa over a 5-year period after the initiation of a large national -------------------------------------------------------------------------------------------------------------- 49 / 57 EUROPRISE SCIENCE UPDATE 12-21 antiretroviral treatment program. Analysis of TDR data from 9 surveys conducted between 2005 and 2009 in 2 provinces of South Africa suggests that while TDR remains low (<5%) in Gauteng Province, it may be increasing in KwaZulu-Natal, with the most recent survey showing moderate (5%-15%) levels of resistance to the nonnucleoside reverse transcriptase inhibitor drug class Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 544199 -----------------------------------------------------81 Virology, resistance Transmitted HIV Drug Resistance Among Drug-Naive Subjects Recently Infected With HIV in Mexico City: A World Health Organization Survey to Classify Resistance and to Field Test Two Alternative Patient Enrollment Methods BERTAGNOLIO S, Rodriguez-Diaz RA, Fuentes-Romero LL, Bennett DE, Viveros-Rogel M, Hart S, Pilon R, Sandstrom P, and Soto-Ramirez LE Clin Infect Dis ,54 Suppl 4, S328-S333 ,2012 AD World Health Organization, Geneva, Switzerland eng PT - Journal Article In 2004, the World Health Organization performed a survey to assess transmitted drug resistance in Mexico City among drug-naive persons with newly diagnosed human immunodeficiency virus (HIV) infection and likely to be recently infected who were attending 3 voluntary counseling and testing sites. A parallel study comparing 2 alternative methods of enrolling survey participant was conducted in 9 voluntary counseling and testing sites in central Mexico. In study arm 1, subject information, consent and blood specimens were obtained during the HIV diagnostic testing visit. In study arm 2, consent and blood specimens were obtained at the return visit, only from those who were HIV infected. This survey classified nonnucleoside reverse-transcriptase inhibitor and nucleoside reversetranscriptase inhibitor transmitted drug resistance as <5% and 5%-15%, respectively. Arm 2 yielded major advantages in cost and workload, with no evidence of increased sampling bias Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 544198 -----------------------------------------------------82 Virology, resistance Prevalence of Transmitted HIV Drug Resistance Among Newly Diagnosed Antiretroviral Therapy-Naive Pregnant Women in Lilongwe and Blantyre, Malawi WADONDA-KABONDO N, Banda R, Moyo K, M'bang'ombe M, Chiwaula M, Porter C, and Jordan MR Clin Infect Dis ,54 Suppl 4, S324-S327 ,2012 AD Community Health Sciences Unit, Ministry of Health, Lilongwe, Malawi eng PT - Journal Article In 2006, a survey of transmitted human immunodeficiency virus (HIV) drug resistance (TDR) was conducted in Lilongwe, Malawi. The survey followed the World Health Organization method to classify TDR to nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs) among primigravid women aged <25 years. Results of the 2006 survey showed <5% TDR in all drug classes. In 2009, TDR surveys using the -------------------------------------------------------------------------------------------------------------- 50 / 57 EUROPRISE SCIENCE UPDATE 12-21 same method were repeated in Lilongwe and expanded to Blantyre. Findings show that in Lilongwe TDR to NRTIs and PIs was <5%, whereas TDR to NNRTIs was 5%-15%. In Blantyre, TDR was <5% to all drug classes. Observed moderate TDR in Lilongwe is cause for concern and signals the need for closer monitoring of Malawi's antiretroviral therapy program Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 544197 -----------------------------------------------------83 Virology, resistance Surveys of Transmitted HIV Drug Resistance in 7 Geographic Regions in China, 2008-2009 LIAO L, Xing H, Dong Y, Qin G, Ma Y, Lu H, Chen L, Zhang L, Osborne C, Seguy N, Wei D, Sun F, Yang J, Ruan Y, and Shao Y Clin Infect Dis ,54 Suppl 4, S320-S323 ,2012 AD State Key Laboratory for Infectious Disease Prevention and Control eng PT - Journal Article In 2003, antiretroviral therapy became available free of charge in China's public health sector. During 2008 and 2009, 10 surveys to classify transmitted human immunodeficiency virus drug resistance (HIVDR) were conducted in 7 regions in 5 provinces (autonomous regions and municipalities) according to World Health Organization guidance. In 2008, transmitted HIVDR was classified as low (<5%) to nucleoside reverse-transcriptase inhibitors, nonnucleoside reverse-transcriptase inhibitors, and protease inhibitors in 6 surveys performed in 6 regions. In 2009, 3 of 4 surveys showed low rates of transmitted HIVDR to all drug classes, and 1 survey showed moderate (5%-15%) rates of transmitted protease inhibitor resistance. In China, routine surveillance of transmitted HIVDR should continue and be expanded to other regions of the country Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 544196 -----------------------------------------------------84 Virology, resistance Surveillance of Transmitted Drug-Resistant HIV Among Young Pregnant Women in Ouagadougou, Burkina Faso SOMDA A, Sangare L, Soro M, Yameogo S, Bazie B, Bigirimana F, Bertagnolio S, Peeters M, Mouacha F, Rivera AM, Jordan MR, and Sanou MJ Clin Infect Dis ,54 Suppl 4, S317-S319 ,2012 AD Ministry of Health/BFA, HIV Surveillance eng PT - Journal Article Burkina Faso began rapid antiretroviral therapy (ART) scale-up in 2003 and by December 2009, 26 448 individuals were on treatment. With rapid scale-up of ART, some degree of human immunodeficiency virus transmitted drug resistance (TDR) is inevitable. Following World Health Organization methods, between June 2008 and July 2009, Burkina Faso assessed TDR in primigravid pregnant women aged <25 years attending antenatal care clinics in Ouagadougou, Burkina Faso. TDR was classified as moderate (5%-15%) for both nucleoside reverse-transcriptase inhibitors and nonnucleoside reversetranscriptase inhibitors. The observed moderate TDR in Ouagadougou is a cause for concern and calls for closer monitoring of Burkina Faso's ART program -------------------------------------------------------------------------------------------------------------- 51 / 57 EUROPRISE SCIENCE UPDATE 12-21 Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 544195 -----------------------------------------------------85 Virology, resistance Monitoring of Early Warning Indicators for HIV Drug Resistance in Antiretroviral Therapy Clinics in Zimbabwe DZANGARE J, Gonese E, Mugurungi O, Shamu T, Apollo T, Bennett DE, Kelley KF, Jordan MR, Chakanyuka C, Cham F, and Banda RM Clin Infect Dis ,54 Suppl 4, S313-S316 ,2012 AD Ministry of Health and Child Welfare eng PT - Journal Article Monitoring human immunodeficiency virus drug resistance (HIVDR) early warning indicators (EWIs) can help national antiretroviral treatment (ART) programs to identify clinic factors associated with HIVDR emergence and provide evidence to support national program and clinic-level adjustments, if necessary. World Health Organization-recommended HIVDR EWIs were monitored in Zimbabwe using routinely available data at selected ART clinics between 2007 and 2009. As Zimbabwe's national ART coverage increases, improved ART information systems are required to strengthen routine national ART monitoring and evaluation and facilitate scale-up of HIVDR EWI monitoring. Attention should be paid to minimizing loss to follow-up, supporting adherence, and ensuring clinic-level drug supply continuity Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 544194 -----------------------------------------------------86 Virology, resistance Combining Cohort Analysis and Monitoring of HIV Early-Warning Indicators of Drug Resistance to Assess Antiretroviral Therapy Services in Vietnam DO TN, Nguyen TM, Do MH, Masaya K, Dang TB, Pham TL, Yoshikawa K, Cao TT, Nguyen TT, Bui DD, Nguyen VK, Nguyen TL, and Fujita M Clin Infect Dis ,54 Suppl 4, S306-S312 ,2012 AD Vietnam Authority of HIV/AIDS Control, Ministry of Health eng PT - Journal Article Antiretroviral therapy (ART) retention and 5 early-warning indicators (EWIs) of HIV drug resistance (HIVDR) were abstracted at 27 adult and 4 pediatric clinics in Vietnam in 2009. Of 4531 adults and 313 children, 81.2% and 84.4% respectively were still on ART at 12 months. More than 90% of the clinics monitored achieved the World Health Organization (WHO) targets for lost-to-follow-up (LTFU), ART prescribing practices, and ARV supply continuity. Only 83.9% of the clinics met the target for first-line ART retention and 79.3% met the target for clinic appointment-keeping. Clinic factors (i.e. number of patients, administrative level, and geographical region) were associated with ART retention and LFTU. Data were useful in guiding public health action to optimize ART services Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 544193 -------------------------------------------------------------------------------------------------------------- 52 / 57 EUROPRISE SCIENCE UPDATE 12-21 -----------------------------------------------------87 Virology, resistance Experience in Piloting HIV Drug Resistance Early Warning Indicators to Improve the Antiretroviral Program in Papua New Guinea DAONI E, Kitur U, Parunga A, Ndenzako F, Lloyd A, and Yu D Clin Infect Dis ,54 Suppl 4, S303-S305 ,2012 AD - HIV/AIDS Program, National Department of Health, Waigani, National Capital District, Papua New Guinea eng PT - Journal Article In 2009, World Health Organization human immunodeficiency virus drug resistance early warning indicator monitoring was piloted at 2 large antiretroviral therapy (ART) clinics in Papua New Guinea: Heduru Clinic in Port Moresby and Tininga Clinic in Mount Hagen. Results demonstrated that both Heduru and Tininga clinics met internationally suggested targets for prescribing appropriate first-line ART regimens in accordance with national ART guidelines, retention on first-line ART at 12 months, and drug supply continuity. However, both clinics failed to achieve suggested targets for rates of loss to follow-up and on-time pill pickup. Reasons for poor clinic performance on loss to follow-up and ontime pill pickup were explored, and appropriate corrective actions were implemented Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 544192 -----------------------------------------------------88 Virology, resistance Monitoring HIV Drug Resistance Using Early Warning Indicators in China: Results From a Pilot Survey Conducted in 2008 MA Y, Zhang F, Li H, Wu H, Zhang J, Ding Y, Zhao D, Fang H, Zhou S, Liu Z, Zhang L, Osborne C, Seguy N, and Zhao Y Clin Infect Dis ,54 Suppl 4, S300-S302 ,2012 AD - Division of Treatment and Care, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing eng PT - Journal Article Robust programmatic monitoring of factors associated with the emergence of human immunodeficiency virus (HIV) drug resistance is an essential component of antiretroviral therapy (ART) program evaluation and treatment optimization. China piloted World Health Organization HIV drug resistance early warning indicators to assess the feasibility and usefulness of results. Overall, early warning indicator monitoring showed high levels of appropriate ART prescribing, low rates of loss to follow-up 12 months after ART initiation, and high rates of retention of first-line ART at 12 months. On-time drug pick-up, which may signal treatment interruptions, was identified as a challenge. HIV drug resistance early warning indicator monitoring provides a valuable assessment of ART service delivery, and its application will be scaled up throughout China Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 544191 ------------------------------------------------------ -------------------------------------------------------------------------------------------------------------- 53 / 57 EUROPRISE SCIENCE UPDATE 12-21 89 Virology, resistance Implementing Early-Warning Indicators of HIV Drug Resistance in the Caribbean JACK N, Ravasi G, Schrooten W, Sutherland D, Ghidinelli M, and Del Riego A Clin Infect Dis ,54 Suppl 4, S290-S293 ,2012 AD - HIV Caribbean Office, Pan American Health Organization, Port of Spain, Trinidad and Tobago eng PT - Journal Article A key component of the World Health Organization's (WHO's) Global HIV Drug Resistance (HIVDR) prevention and assessment strategy is to monitor HIVDR early-warning indicators (EWIs), which provide strategic information for HIVDR containment. The Pan American Health Organization (PAHO)/WHO supported implementation of HIVDR EWI monitoring in 16 Caribbean countries. Results from 15 countries were analyzed by year of patient initiation of antiretroviral therapy for the period 2005-2009. This report demonstrates the need for capacity-building to standardize prescribing practices and to strengthen adherence strategies and antiretroviral drug procurement management systems Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 544189 -----------------------------------------------------90 Virology, resistance HIV Drug Resistance Early Warning Indicators in Cohorts of Individuals Starting Antiretroviral Therapy Between 2004 and 2009: World Health Organization Global Report From 50 Countries BENNETT DE, Jordan MR, Bertagnolio S, Hong SY, Ravasi G, McMahon JH, Saadani A, and Kelley KF Clin Infect Dis ,54 Suppl 4, S280-S289 ,2012 AD US Centers for Disease Control and Prevention, Atlanta, Georgia eng PT - Journal Article The World Health Organization developed a set of human immunodeficiency virus drug resistance (HIVDR) early warning indicators (EWIs) to assess antiretroviral therapy clinic and program factors associated with HIVDR. EWIs are monitored by abstracting data routinely recorded in clinical records, and the results enable clinics and program managers to identify problems that should be addressed to minimize preventable emergence of HIVDR in clinic populations. As of June 2011, 50 countries monitored EWIs, covering 131 686 patients initiating antiretroviral treatment between 2004 and 2009 at 2107 clinics. HIVDR prevention is associated with patient care (appropriate prescribing and patient monitoring), patient behavior (adherence), and clinic/program management efforts to reduce treatment interruptions (follow up, retention on first-line ART, procurement and supply management of antiretroviral drugs). EWIs measure these factors and the results have been used to optimize patient and population treatment outcomes Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 544188 ------------------------------------------------------ -------------------------------------------------------------------------------------------------------------- 54 / 57 EUROPRISE SCIENCE UPDATE 12-21 91 Virology, resistance Genotyping External Quality Assurance in the World Health Organization HIV Drug Resistance Laboratory Network During 20072010 PARKIN N, Bremer J, and Bertagnolio S Clin Infect Dis ,54 Suppl 4, S266-S272 ,2012 AD HIV Department, World Health Organization, Geneva, Switzerland eng PT - Journal Article The World Health Organization (WHO) has developed a global laboratory network to support human immunodeficiency virus drug resistance genotyping for public health surveillance in resource-limited countries. Blinded proficiency panels are an essential part of a genotyping quality-assurance program and are used to monitor the reliability of genotyping data in the WHO laboratory network. Laboratories in Europe, North America, Asia, Africa, and the Caribbean have tested panels annually since 2007; 103 of 131 submissions (79%) had >99% nucleotide sequence identity and resistance mutation concordance, compared with consensus. Most errors were associated with mixtures in the test specimen, leading to subjectivity in base-calling or amplification bias. Overall, genotyping assays used by the WHO laboratory network are reliable Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 544186 -----------------------------------------------------92 Virology, resistance Are Countries Using Global Fund Support to Implement HIV Drug Resistance Surveillance? A Review of Funded HIV Grants KELLEY KF, Caudwell E, Xueref S, Ha TH, and Bertagnolio S Clin Infect Dis ,54 Suppl 4, S250-S253 ,2012 AD World Health Organization eng PT - Journal Article The Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund) is the largest funder of human immunodeficiency virus (HIV) prevention and treatment programs worldwide. Since 2002, the Global Fund has encouraged grant recipients to implement drug resistance surveillance (DRS) as part of treatment programs. We reviewed documentation of 147 grants funded in 2004-2008 (funding rounds 4-8) to assess grantees' use of funds to support HIV DRS. Overall, 94 grants (64%) described HIV DRS as part of the national treatment program. However, only 32 grants (22%) specifically documented DRS as a grant-funded activity. This review provides baseline information suggesting limited use by countries of Global Fund financing to support HIV DRS. Additional assessment is required to evaluate barriers to using Global Fund grants to support DRS Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 544183 ------------------------------------------------------ -------------------------------------------------------------------------------------------------------------- 55 / 57 EUROPRISE SCIENCE UPDATE 12-21 93 Virology, resistance Update on World Health Organization HIV Drug Resistance Prevention and Assessment Strategy: 2004-2011 JORDAN MR, Bennett DE, Wainberg MA, Havlir D, Hammer S, Yang C, Morris L, Peeters M, Wensing AM, Parkin N, Nachega JB, Phillips A, De Luca A, Geng E, Calmy A, Raizes E, Sandstrom P, Archibald CP, Perriens J, McClure CM, Hong SY, McMahon JH, Dedes N, Sutherland D, and Bertagnolio S Clin Infect Dis ,54 Suppl 4, S245-S249 ,2012 AD World Health Organization, Geneva, Switzerland eng PT - Journal Article The HIV drug resistance (HIVDR) prevention and assessment strategy, developed by the World Health Organization (WHO) in partnership with HIVResNet, includes monitoring of HIVDR early warning indicators, surveys to assess acquired and transmitted HIVDR, and development of an accredited HIVDR genotyping laboratory network to support survey implementation in resource-limited settings. As of June 2011, 52 countries had implemented at least 1 element of the strategy, and 27 laboratories had been accredited. As access to antiretrovirals expands under the WHO/Joint United Nations Programme on HIV/AIDS Treatment 2.0 initiative, it is essential to strengthen HIVDR surveillance efforts in the face of increasing concern about HIVDR emergence and transmission Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 544182 -----------------------------------------------------94 Virology, resistance The World Health Organization HIV Drug Resistance Prevention and Assessment Strategy: Global, Regional, and Country Progress Clin Infect Dis ,54 Suppl 4, NP ,2012 eng PT Journal ArticleLink : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 544175 -----------------------------------------------------95 Virology, resistance [Survey on the Transmission of HIV Drug Resistance in Kunming, Yunnan Province in 2010] CHEN M, Ma YL, Chu CX, Xing H, Xu YS, Su YZ, Yang Y, Chen HC, Luo HB, Jia MH, and Lu L Zhonghua Liu Xing Bing Xue Za Zhi ,33 (1), 75-77 ,2012 AD - Yunnan Center for Disease Control and Prevention, Kunming 650022, China chi PT English Abstract PT - Journal Article OBJECTIVE: To study the HIV drug resistance (HIVDR) transmission in Kunming city of Yunnan province in 2010. METHODS: Referring to the guidelines for HIV drug resistance threshold survey (HIVDR-TS) set by WHO, 62 plasma samples of recently reported HIV-infected individuals who were older than 25 years of age, were collected from January to August 2010. Genotyping of pol genetic mutations associated with HIVDR with reverse transcriptional PCR was performed and the prevalence of HIV-1 drug resistance transmission was evaluated. RESULTS: Of the 62 plasma samples, 54 were -------------------------------------------------------------------------------------------------------------- 56 / 57 EUROPRISE SCIENCE UPDATE 12-21 successfully sequenced and genotyped on pol sequence. Based on the pol sequences, HIV subtypes including CRF08_BC (53.2%), CRF07_BC (25.5%), CRF01_AE (19.1%) and C (2.1%) were identified. According to the time of sampling, the first 47 sequenced samples were used for drug resistance prevalence analysis. A protease inhibitor (PI) relative mutation was found in one sample. Based on the WHO standard, the prevalence of transmitted HIV-1 drug resistance was < 5%. CONCLUSION: HIV-1 drug resistant strains transmission was still catalogued as low prevalence level in Kunming. To prevent the increase of HIVDR prevalence, normative treatment and scientific management to AIDS patients seemed to be quite important Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 575116 -----------------------------------------------------96 Virology, resistance Prevalence of Drug Resistance and Associated Mutations in a Population of HIV-1(+) Puerto Ricans: 2006-2010 SEPULVEDA-TORRES LDEL C, De La Rosa A, Cumba L, Boukli N, Rios-Olivares E, and Cubano LA AIDS Res Treat ,2012, 934041 ,2012 AD - Department of Microbiology and Immunology, Universidad Central del Caribe, PO Box 60327, Bayamon, PR 00960-6032, USA eng PT - Journal Article This is a continuation of our efforts to maintain a record of the evolution of HIV-1 infection in Puerto Rico by monitoring the expression levels of antiretroviral drug-resistance-associated mutations. Samples from 2,500 patients from 2006-2010 were analyzed using the TruGene HIV-1 genotyping kit and the OpenGene DNA sequencing system. Results show that 58.8% of males and 65.3% of females had HIV-1 with resistance to at least one medication. The average number of HIV mutations was 6.0 in males and 6.1 in females. Statistically significant differences between men and women were recorded in the levels of HIV-1 expressed mutations and antiretroviral drug resistance. The most prevalent antiretroviral medication resistance shifted from zalcitabine to nevirapine and efavirenz in the fiveyear period. M184V and L63P were the dominant mutations for the reverse transcriptase and the protease genes, respectively, but an increase in the incidence of minority mutations was observed Link : http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=pubmed&dopt=Citation&list_uids=22 593823 ------------------------------------------------------ -------------------------------------------------------------------------------------------------------------- 57 / 57
