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Clinical HIV infection Gail Crowe Princess Alexandra Hospital 2003/04 1 Objectives Epidemiology Natural history Seroconversion Testing for HIV HIV indicator diseases Treatment 2003/04 2 Global Estimates for Adults and Children 2007 2003/04 4 Estimated Number of People Living With HIV Globally 19902007 2003/04 5 Estimated Number of Adult and Child Deaths Due to HIV Globally 19902007 2003/04 6 Adults and Children Living With HIV Globally 2007 2003/04 7 Estimated number of adults (15-59 years) living with HIV (both diagnosed and undiagnosed) in the UK: 2008 Estimated number of people living HIV 25,000 24,350 Diagnosed Undiagnosed Total = 77,550 (73,000 - 83,300) Excludes 5,450 HIV infections among individuals outside the 15-59 years age range 20,000 15,000 13,850 10,000 8,950 6,550 5,450 5,000 4,050 2,850 4,550 2,250 2,150 1,200 450 550 150 0 MSM 2003/04 Heterosexual men born in Africa Heterosexual Heterosexual Heterosexual women born in men born in women born in Africa UK/elsewhere UK/elsewhere Injecting drug user men Injecting drug user women MESH Department - Centre for Infections 8 Diagnosed HIV-infected persons accessing care by prevention group1 and ethnic group2, UK 20,000 White MSM Black African heterosexuals White heterosexuals Non-white MSM Numbers accessing care 15,000 All other heterosexuals IDU Other 10,000 5,000 0 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 1Numbers 2Ethnic accessing care exclude those where exposure category was not reported (1,552 in 2006) group was allocated proportionally where it was not reported 2003/04 Annual survey of HIV-infected persons accessing care 9 UK number of HIV diagnoses by year of diagnosis 9000 8000 7000 6000 5000 4000 3000 2000 1000 2003/04 07 06 08 20 20 20 05 20 04 20 03 20 02 20 00 01 20 99 20 19 98 19 97 19 96 19 95 93 94 19 19 19 92 19 91 19 90 19 89 19 87 88 19 19 19 86 0 10 Number of new HIV diagnoses¹ by prevention group², UK: 1999-2008 4,500 4,000 New HIV diagnoses 3,500 MSM Heterosexual contact in the UK Heterosexual contact abroad IDU Blood product recipients Mother-to-child transmission 3,000 2,500 2,000 1,500 1,000 500 0 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 ¹ Numbers will rise as further reports are received, particularly for recent years ² Adjustments made for missing information relating to patient exposure MESH Department - Centre for Infections 2003/04 11 Estimated late diagnosis of HIV infection by prevention group among adults aged ≥ 15 years, UK: 2008 100% CD4 cell counts <200 cells/mm³ within three months of diagnosis 90% <200 Percentage diagnosed late 80% <350 70% 65% 61% 60% 55% 52% 50% 43% 44% 40% 36% 30% 32% 30% 20% 20% 10% 0% MSM Number diagnosed = 2,760 Heterosexual men 1,630 Heterosexual women Injecting drug users 2,950 170 Overall 7,218 MESH Department - Centre for Infections 2003/04 12 HIV in the UK: 2008 83,000 living with HIV 40% of HIV probably acquired in UK 2/3 of these are in gay men 31% of new diagnoses “late” 22,400 unaware of diagnosis ie CD4 <200 56,556 HIV+ people accessed care 2003/04 70% on ARVs 8% >55 yrs old 14 HIV Attendances at PAH 160 140 120 100 3-D Column 1 80 60 40 20 0 1997 2003/04 1999 2001 2003 2005 2007 2009 15 HIV Attendances by Risk Factor 100 90 80 70 60 50 40 30 20 10 0 Gay men Black African IVDU White Heterosexual Other 1997 1999 2001 2003 2005 2007 2009 2003/04 16 Attendances by CDC Grade 120 100 80 A B C 60 40 20 0 1997 2003/04 1999 2001 2003 2005 2007 2009 17 Natural history Over course of infection: CD4 count declines & HIV viral load increases Increasing risk of developing infections and tumours The severity of these illnesses is greater the lower the CD4 count Most AIDS diagnoses occur at CD4 count <200 2003/04 18 Natural history Acute infection – seroconversion Asymptomatic HIV related illnesses AIDS defining illness Death 2003/04 19 Primary HIV / seroconversion 2003/04 Approximately 30 - 60% of patients have a seroconversion illness. Abrupt onset 2 – 4 weeks post exposure, self limiting 1 – 2 weeks Symptoms generally non-specific and differential diagnosis includes range of common conditions Serological tests for HIV antibodies may be negative or show indeterminate response 20 Symptoms include: 2003/04 Flu-like illness Fever Malaise and lethargy Pharyngitis Lymphadenopathy Toxic exanthema Occasionally HIV / AIDS defining illness due to profound damage to immune system (often temporary) e.g. oro-pharyngeal candida, zoster, PCP 21 Natural history Acute infection – seroconversion Asymptomatic HIV related illnesses AIDS defining illness Death 2003/04 22 HIV associated conditions Most of these conditions are common in the general population. Think of HIV if presentation is: atypical recurrent problem severe Suspicion may be increased if the individual is at possible risk of HIV infection 2003/04 23 Healing herpes zoster Picture from St George’s Hospital for educational use only 2003/04 24 Oral Candida 2003/04 Picture from St George’s Hospital for educational use only 25 Severe oral hairy leukoplakia Picture from St George’s Hospital for educational use only 2003/04 26 Symptoms and parameters over time Opportunistic Infections Symptomatic HIV Infection 0 2003/04 HIV RNA HIV ab CD4 Time 27 Treatment for HIV Monotherapy Dual therapy Triple / quadruple therapy 2003/04 28 Treatment for HIV (2) Nucleoside / nucleotide reverse transcriptase inhibitors (Nucs) Non nucleoside reverse transcriptase inhibitors (NNRTI) Protease inhibitors (PI) Fusion inhibitors Integrase inhibitors CCR5 inhibitors 2003/04 29 Treatment for HIV (3) Nucs: AZT, 3TC, , Abacavir, DDI, D4T, FTC, Tenofovir NNRTIs: Efavirenz, Nevirapine, Etravirine PIs: Lopinavir, Atazanavir, Darunavir, Amprenavir, Saquinavir, Indinavir, Ritonavir Fusion Inhibitors: T20 Integrase Inhibitors: Raltegravir CCR5 Inhibitors: Maraviroc 2003/04 30 Side Effects of Treatment Nausea and vomiting, diarrhoea Anaemia / pancytopaenia / abn LFTs Insomnia Rash Lipodystrophy Pancreatitis, peripheral neuropathy, lactic acidosis, renal stones 2003/04 31 Monitoring Treatment See 3 monthly Viral load CD4 count Resistance tests Therapeutic drug monitoring 2003/04 32 BHIVA Guidelines Launched September 2008 Suggest HIV testing should be offered and recommended in 2003/04 Gay men Intravenous drug users People from high prevalence areas (sub Saharan Africa) Sexual partners of the above 33 Risk Assessment Gay men – London Gay men – outside London IVDU – London IVDU – not London Sub-Saharan Africa 2003/04 19.1% 4.3% 3.5%(M) 5.0%(F) 0.77%(M) 0.34%(F) 5.8%(M) 8.9% (F) 34 BHIVA Guidelines Also suggest universal testing in 2003/04 GUM clinics Antenatal services TOP services Drug dependency units TB units Patients with Hepatitis B Patients with Hepatitis C Patients with lymphoma 35 BHIVA Guidelines Also suggest universal testing in 2003/04 GUM clinics Antenatal services TOP services Drug dependency units TB units Patients with Hepatitis B Patients with Hepatitis C Patients with lymphoma ✔ ✔ ✔ ✔ ✔ ✘ ✘ ✘ 36 BHIVA Guidelines Suggest that where an HIV indicator disease is present, then testing should be offered 2003/04 37 Clinical Indicator Disease for HIV TB PCP Toxo Cerebral lymphoma Crypto meningitis PML 2003/04 Bacterial pneumonia Aspergillosis Aseptic meningitis Encephalitis SOL Cerebral abscess Guillain Barre Dementia Peripheral neuropathy Transverse myelitis 38 Clinical Indicator Disease for HIV KS Cryptospoidiosis 2003/04 Seb dermatitis Severe psoriasis Severe shingles Oral candida OHL Persistent diarrhoea Shigella, Campylobacter, Salmonella Unexplained wt loss Hep B, Hep C 39 Kaposi’s sarcoma Picture from St George’s Hospital for educational use only 2003/04 40 Clinical Indicator Disease for HIV KS Cryptospoidiosis 2003/04 Seb dermatitis Severe psoriasis Severe shingles Oral candida OHL Persistent diarrhoea Shigella, Campylobacter, Salmonella Unexplained wt loss Hep B, Hep C 41 Clinical Indicator Disease for HIV NHL Cervical cancer 2003/04 Hodgkins lymphoma Lung ca Anal cancer / AIN Head and neck cancers Seminoma Castlemans disease VIN CIN 2 or above Thrombocytopenia, neutropenia, 42 Clinical Indicator Disease for HIV CMV retinitis 2003/04 Infective retinal disease or unexplained retinopathy Unexplained lyphadenopathy Chronic parotitis “Glandular fever” PUO Any STI 43 BHIVA Guidelines on HIV Testing Suggest that, where prevalence of HIV exceeds 2/1000 consideration should be given to testing 2003/04 all medical admissions all patients registering with a GP 44 HIV Prevalence By PCT PCT Number accessing HIV care Population in HIV 1000s prevalence per 1000 Lambeth 2,339 196.2 11.9 Tower Hamlets 836 152 5.5 Southend 259 93.8 2.76 Harlow 101 48 2.1 2003/04 45 HIV – pre test discussion Informed consent Advantages and disadvantages Risk assessment 3 month window period Preparing for the result Getting the result Health promotion 2003/04 46 Raising the subject of an HIV test Communication strategies Raising the subject of HIV with a patient can be difficult. ‘The problems that you have had recently are quite common, and usually minor. However, very occasionally they can give a clue that your immune system is not working as well as it should.’ ‘I don’t know if you are at risk of HIV, but this is one condition that can affect the immune system. Could I ask you some questions to see if you could be at risk?’ . 2003/04 47 Raising the subject of an HIV test Communication strategies 2003/04 • Raise the subject of HIV before a sexual history has been taken – perhaps in a contraception or smear consultation. ‘HIV is much more common in people from Africa. Do you know people who have been affected? Would you like to consider having a test?’ • Raise the subject of sexual health in a new patient check. ‘We find that quite a lot of young men are at risk of having sexual health problems. Could I ask you a few questions to see if you are at risk?’ 48 Raising the subject of an HIV test Communication strategies • Raise the subject of HIV once a sexual history has been taken. ‘Because two of your partners in the last year have been male, like you, it is possible that you are at higher risk of HIV. Have you ever considered having an HIV test?’ • Raise the subject of HIV when a history of injecting drug use has been identified. ‘Current advice is that everyone who has injected drugs in the past should be offered a test for HIV. Have you ever considered having a test?’ • Remember to emphasise the benefits of earlier HIV diagnosis. 2003/04 49 Risk Assement Sexual behaviour and that of partners Nationality, country of exposure History of IVDU Rape/sexual assault Occupational exposure Invasive procedures in unsterile conditions Blood/blood products / organ recipient 1975-1985 (UK) 2003/04 50 Medical benefits of early HIV diagnosis Treatments available (HAART) not cure, but prevent people becoming unwell Prophylaxis against opportunistic infections if appropriate Appropriate investigations if unwell Reduce perinatal transmission 2003/04 treatment for mother delivery method avoidance of breastfeeding (in UK) 51 Other benefits Minimise the risk of infecting others Partner notification Ability to inform important life decisions Relief of anxiety about knowing HIV status Access to help from social services, drug services etc 2003/04 52 Case Presentation 1 S.J 26 yr old woman from Sierra Leone Attended GP with 6/52 hist of fever, intermittent cough, cervical lymphadenopathy Nine months previously had seen GP with fatigue and was found to have mild anaemia Now Rx Penicillin – helped initially but fevers returned 2003/04 53 Admitted to hospital with PUO Temp 39 C, P100, BP 85/50 LN all areas, 3 cm hepar Rx multiple ab – no or temp effect Reluctantly agreed to HIV test – pos Eventually diagnosed with TB on sputum culture Had visited GP regularly over past 9 months c/o fatigue / malaise for which only Ix had been FBC 2003/04 54 Case Presentation 2 Mr S.S. 53 yr old salesman, recently separated from wife since 2000 Unwell for several yrs Admitted Addenbrookes Jan 2006 with ?EBV/?CMV and abn LFTs Seen by GP June 2007 with fatigue / malaise Pancytopenia 2003/04 55 Discussed with Haematologist – told “no indication to do HIV test”! Transferred to different GP in B/S Still pancytopenia Now also oral Candida and wt loss Jan 2008, sent for HIV test – pos CD4 80 Started ARV and doing well 2003/04 56 Case Presentation 3 M.C. 36 year old Zimbabwean woman Diagnosed March 2007 CD4 0 Spent 41 days in PAH (£6,769) Transferred to BLT – further 9 months as inpatient (£63,720) Total £70,489 Died 2003/04 57 The Cost of Late Diagnosis 2007: 249 HIV bed-days 231/249 directly related to late diagnosis Total cost £54,072 (Cost of HIV test: £3.30) 2003/04 58 Summary Natural history Benefits of knowing status Seroconversion Other indicators of HIV infection - when to think of HIV Treatment and monitoring 2003/04 59 Where to Look for Help http://www.medfash.org.uk Has produced excellent booklet on HIV in Primary Care available free from website http://www.bhiva.org 2003/04 For testing and treatment guidelines 60