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HIV/AIDS in Practice An Expert Commentary With Carl Dieffenbach, PhD A Clinical Context Report Clinical Context: HIV/AIDS in Practice Expert Commentary Jointly Sponsored by: and Clinical Context: HIV/AIDS in Practice Expert Commentary This activity is supported by an independent educational grant from Bristol-Myers Squibb. HIV/AIDS in Practice Clinical Context Series The goal of this series is to provide up-todate information and multiple perspectives on the pathogenesis, symptoms, risk factors, and complications of HIV/AIDS, as well as current and emerging treatments and best practices in the management of HIV/AIDS. HIV/AIDS in Practice Clinical Context Series Target Audience HIV/AIDS specialists, virologists, infectious disease specialists, primary care physicians, nurses, nurse practitioners, physician assistants, pharmacists, and other healthcare professionals involved in the management of HIV/AIDS Activity Learning Objective CME Information: Physicians • Statement of Accreditation This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Projects In Knowledge and MedPage Today. Projects In Knowledge is accredited by the ACCME to provide continuing medical education for physicians. CME Information • Credit Designation Projects In Knowledge designates this educational activity for a maximum of 0.5 AMA PRA Category 1 Credits.™ Physicians should claim only the credit commensurate with the extent of their participation in the activity. CME Information: Physicians • Credit for Family Physicians MedPage Today "News-Based CME" has been reviewed and is acceptable for up to 2098 Elective credits by the American Academy of Family Physicians. AAFP accreditation begins January 1, 2011. Term of approval is for one year from this date. Each article is approved for 0.5 Elective credits. Credit may be claimed for one year from the date of each article. CE Information: Nurses • Statement of Accreditation – Projects In Knowledge, Inc. (PIK) is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation. – Projects In Knowledge is also an approved provider by the California Board of Registered Nursing, Provider Number CEP-15227. – This activity is approved for 0.50 nursing contact hours. – There is no fee for this activity. DISCLAIMER: Accreditation refers to educational content only and does not imply ANCC, CBRN, or PIK endorsement of any commercial product or service. CE Information: Pharmacists • Projects In Knowledge® is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. This program has been planned and implemented in accordance with the ACPE Criteria for Quality and Interpretive Guidelines. This activity is worth up to 0.5 contact hours (0.05 CEUs). The ACPE Universal Activity Number assigned to this knowledge-type activity is 0052-9999-11-2108-H04-P. Discussant Carl W. Dieffenbach, PhD Director Division of AIDS (DAIDS) National Institute of Allergy & Infectious Diseases (NIAID) National Institutes of Health (NIH) Bethesda, Maryland Disclosure Information Carl W. Dieffenbach, PhD, has disclosed that he has no relevant financial relationships or conflicts of interest to report. Disclosure Information Dori F. Zaleznik, MD, Associate Clinical Professor of Medicine, Harvard Medical School, Boston; Michael Smith; and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner, have disclosed that they have no relevant financial relationships or conflicts of interest with commercial interests related directly or indirectly to this educational activity. The staffs of Projects In Knowledge and MedPage Today have no relevant financial relationships or conflicts of interest with commercial interests related directly or indirectly to this educational activity. Seminal/Vaginal FluidSSe Prevent contact with HIV Prevent contact with HIV Barrier methods Reduce/eliminate infectivity from the source ART as prevention reduces the amount of virus in secretions Reduce target cell susceptibility Prophylaxis with ART Acute HIV-1 Infection Virus Concentration in Extracellular Fluid or Plasma (Copies/ml) plasma gp41 Antibody, Day 13 (Non-Neutralizing) 108 Autologous gp120 Neutralizing Antibody 11 Weeks ? Delay 107 106 105 104 eclipse 103 102 CD8 T Cell Responses 101 0 10-1 10-2 Transit 10-3 T0 Autologous Neutralizing Antibody Escape (new Plasma virus mutants) Virus (new virus mutants) dissemination 10-4 10-5 0 Transmission 5 10 15 20 25 30 35 40 45 50 55 60 65 70 Time Post Exposure (days) T Cell Induced Mutations No Antibody Induced Mutations First Definite Antibody Induced Mutations Establishment of a Pool of LatentlyInfected, Resting CD4+ T Cells During Primary HIV Infection HIV Replication Cycle fusion binding core and preintegration complex reverse transcription APOBEC uncoating TRIM5α nuclear import transcription mRNA translation integration assembly coreceptor CD4 APOBEC Vif budding HIV Replication Cycle fusion binding core and preintegration complex reverse transcription APOBEC uncoating TRIM5α nuclear import transcription mRNA translation integration assembly coreceptor CD4 APOBEC Vif budding A Cure for HIV Infection The problem: current HIV therapy, while effective, is merely suppressive Summary At the end of this activity, participants should understand: • HIV targets activated CD4-positive T cells • Transmission is made easier by breaks in the genital and anal mucosa • HIV forms a reservoir in lymphoid tissue early in the course of infection Summary • The course of untreated infection includes a period of latency of months or years during which a patient may have few or no symptoms • The HIV replication cycle offers several targets for intervention, including reverse transcription, maturation, entry, and integration