HIV & AIDS

1. HIV & AIDS YP Beh ST6 GUM Coventry & Warwickshire PT 19.6.12

2. Objectives • Biology of HIV Virus • Epidemiology • Clinical Presentations • HIV Testing • HIV and Antiretroviral Treatment • Chronic HIV associated conditions • HIV and Pregnancy • Post exposure prophylaxis for HIV

3. Biology of HIV 1 • HIV is a retrovirus • It cannot replicate by itself and must utilise host cell machinery in order to produce new virus particles • It can convert its RNA genome into DNA • HIV DNA integration into the host cell genome allows it to access host biochemical pathways to reproduce • The RNA – DNA reaction is catalysed by reverse transcriptase • HIV DNA is subsequently integrated into the host cell’s genome

4. HIV life cycle • http://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter24/animation__how_the_hiv_infection_cycle_works.html

7. CD4 & Viral Load CD4 Lymphocyte count Normal Value 500 -1200 cells Indication ‘strength’ of the immune system AIDS if CD4 less than 200 cells Viral Load The amount of HIV Virus in the blood Measurement of viral copies/ml

9. Estimated number of people living with HIV infection: United Kingdom, 2010 Total with HIV = 91,500 (85,400 − 99,000)Total diagnosed = 69,250 (67,800 − 70,800)Total undiagnosed = 22,200 (16,350 − 29,650)

10. New HIV diagnoses by exposure group: United Kingdom, 2001 – 2010

11. Probable recent infection among people newly diagnosed with HIV by exposure group: England and Northern Ireland, 2010

12. New HIV diagnoses by probable country of infection : 2001-2010

13. Late diagnoses of HIV by exposure group: UK, 2010

14. Presentations of HIV • Asymptomatic • Seroconversion period • AIDS-related conditions • Chronic HIV-associated conditions

15. HIV Seroconversion

16. Primary HIV Infection • Two – four weeks post-infection • Symptoms • Fever, maculopapular rash, myalgia, pharyngitis, headache, lymphadenopathy • Varies from very mild to severe enough to require hospital admission • Be aware in high-risk groups! • Highly infectious time because of high viral load • Transient fall in CD4 count can lead to OI

17. HIV and the Lung • Infections • Tuberculosis • Pneumocystis jiroveci pneumonia • Fungal pneumonia • Bacterial pneumonia • Malignancy • Kaposi’s sarcoma • Lymphoma • Non-malignant conditions • Lymphoid interstitial pneumonitis

18. Pulmonary Infections - PCP

19. Pulmonary Infections - TB

20. Lymph nodes TB Lymphoma HIV

21. HIV and the Brain • Opportunistic infections • Toxoplasma gondii - abscesses and encephalitis (<200) • Cryptococcus neoformans - meningitis (<200) • JC virus – Progressive Multifocal Leucoencephalopathy (<100) • CMV - retinitis, encephalitis, mononeuritis multiplex, cauda equina syndrome • Tumours • Primary CNS lymphoma • HIV-related disorders • HIV-associated dementia complex • Peripheral neuropathy (distal sensory polyneuropathy)

22. Progressive multi-focal leuco- encephalopathy (PML)

24. Cryptococcoma

25. HIV & Eye infection Retinitis

26. HIV and the Gut • Oesophageal candidiasis • Infective Diarrhoea • Bacteria e.g. campylobacter, shigella, MAI • Protozoa e.g. cryptosporidium, isospora belli, microsporidium • Viruses e.g. CMV, adenovirus • Malignancy • Kaposis sarcoma • Drug Side-Effects • HIV Wasting Syndrome

27. Oesophageal candidiasis

28. HIV and the Skin • Seborrhoeic dermatitis • Aphthous ulceration • Oral candida (<300) • Kaposi’s Sarcoma (<200) • Bacteria: • Impetigo, folliculitis • Fungi • Tinea pedis, cruris; pityriasis versicolor • Candida - genital, perianal, other • Viruses • HSV 1 and 2 • Varicella zoster • EBV (<300) • HPV • Molluscum contagiosum • Neoplasia • Cervical dysplasia

29. Kaposi’s sarcoma

30. Who should be tested? Opt Out’ for: All patients attending GUM or sexual health clinics. All women attending antenatal services. All women attending termination of pregnancy services. All patients registering with drug dependency programmes reporting a history of injecting drug use. All patients diagnosed with Tuberculosis, Hepatitis B, Hepatitis C and Lymphoma.

31. 4th generation tests eg Determine test Antigen & Antibody detection Previous 3rd gen tests Antibody only (INSTI) All must be confirmed by formal venepuncture HIV Testing

32. BASHH Statement on HIV window period • 4th generation tests are recommended which test for HIV antibodies and p24 antigen simultaneously • They will detect the great majority of individuals who have been infected with HIV 4 weeks after exposure • A negative result at 4 weeks post exposure is very reassuring • An additional HIV test should be offered to all persons at 3 months to definitively exclude HIV infection

33. Highly Active Anti-Retroviral Therapy (HAART) • Suppress Viral Load & Increases CD4 • Combination therapy • HAART Initiation when CD4 <350cells/mm3 • Reduced risk of disease progression • Life expectancy

34. Late 90s Now

36. HAART & the HIV Life Cycle

37. When to start? BHIVA guideline 2008

38. Chronic HIV-Associated Conditions

39. Rate of Heart Attacks in HIV Positive and HIV Negative Patients 100 HIV+ 80 HIV– 60 Events per 1000 Person-Years 40 20 0 45-54 18-34 35-44 55-64 65-74 Age Group (Years) Age Triant VA,et al. J Clin Endocrinol Metab. 2007;92:2506-2512.

41. HIV and Hepatitis B • 100 times more infectious than HIV • 10 times more infectious than HCV • Lives outside the body for up to 7 days

42. Progression of Chronic Hepatitis Liver Cancer (HCC) 5%–10% 10%–15% in 5 yr Liver Transplantation Cirrhosis Death Chronic Infection 30% 23% in 5 yr Liver Failure Adapted from: Fattovich, et al. Gastroenterology. 2004;127:S35-S50. Torresi, et al. Gastroenterology. 2000;118:S83-S103. Fattovich, et al. Hepatology. 1995;21:77-82. Perrillo, et al. Hepatology. 2001;33:424-432.

43. HIV & Bone Disease: Greater risk of fractures in HIV-Infected individuals Fracture prevalence/100 persons p<0.001 Triant VA, Brown TT, Lee H, Grinspoon SK. Fracture prevalence among human immunodeficiency virus (HIV)-infected versus non-HIV-infected patients in a large U.S. healthcare system. J Clin Endocrinol Metab 2008; 93:3499–3504

44. Other chronic co-morbidities with HIV • Cancer • Kidney Disease • Renal function slowly declines with age • Diabetes • Neurocognitive decline

45. HIV and Pregnancy – Reducing VL • When to treat • Continue treatment if conception occurs on HAART • Between 20/40 and 28/40 • Aim for undetectable VL by 36/40 • What to treat with • At least 3 drugs – usually combivir + PIs • ZDV monotherapy

46. HIV and Pregnancy – Post-Delivery • Therapy for baby • 4/52 triple therapy for babies born to mothers with detectable VL • 4/52 ZDV for babies born to mothers with undetectable VL • Recommend EXCLUSIVE formula feeding • Testing baby • Loss of maternal antibody at 18/12 • PCR testing; primers to amplify maternal virus

47. Post-Exposure Prophylaxis PEP consists of 28 days of triple therapy Not licensed Offered only where the risk is high Should be offered within 72 hours Best result within 1 hour of the contact Reduces the risk of transmission by 80% Common side effects are nausea, diarrhoea and fatigue Less common side effects are renal dysfunction, insulin resistance, lipid disorders

48. HIV Transmission

49. Recommended information sources • ABC of AIDS, BMJ Books • www.BHIVA.com • www.aidsmap.com • http://www.hiv-druginteractions.org/ • www.medscape.com

50. Summary • HIV is a treatable condition • Can present with any symptom, or none • People living with HIV in the UK can expect a near-normal life expectancy • Importance of diagnosing early infection