1. An update on HIV prevention and treatment Prof Francois Venter Wits Reproductive Health and HIV Institute (WRHI) University of the Witwatersrand Oct 2012

2. AIDS in Africa

3. Tensions… Prevention versus HIV treatment HIV versus other illnesses Public health versus human rights versus the law Government versus donor responsibility

4. Who is at fault? Politicians and voters Public Health experts Clinicians Researchers Donors

5. Eastern & Southern Africa 1.5 million (57% Rest of the world 1.2 million (43%) Global new infections, 2.7 million ESA new infections, Prov. estimate 1.5m Estimates of New Infections in Eastern and Southern Africa, 2007

6. South Africa Brazil Namibia Chile Measurement of Generally Accepted Indicators Reveals that the South African Healthcare System is Functioning Poorly by International Standards 1,900 1,800 Afghanistan India South Africa Iraq China Namibia Brazil Chile United Kingdom Netherlands 2000 2005 Note: MMR = Number of Maternal deaths per 100,000 *Public Sector deliveries estimated. Live births is used as a proxy for the number of pregnancies annually.MMR is an indicator of the quality of a health care system Source: WHO Maternal Mortality Report, 2007, StatsSA Maternal Mortality Rates by Geography (2000 vs 2005) MDG 2015 Target Trend Projection for Maternal Mortality Rate until 2015 58 2

7. Since the SA ARV rollout started… 2 million people on treatment (& million worldwide) 5 million deaths 5 million new infections

8. Implications HCT campaign 1 st April 2010…. 15 million tests, linked to TB, other chronic illness screening

9. New guidelines

10. CD 4 Gets HIV! Needs ARV’s 8 to 10 years What happens if you get HIV? Wellness – nutrition, exercise, stop smoking, safe sex, mental health, ↓ alcohol

11. How good are the antiretrovirals?

12. Before and after initiation of ARV therapy!

13. Thapelo Before and after initiation of ARV therapy!

14. ART outcomes - good news National programmes reporting good outcomes 1 year survival estimated as 93-95% 2 year survival 91% SA life expectancy up

15. How long will people live for? ? 20 years or more on the treatment package !! – CROI 2005 Danish study – 39 years! American – lose 12 years French – NORMAL after 6 years Uganda – normal! Geriatrics, fertility

16. In summary, what has changed: CD4 350, for all Initiation of infants immediately New maternal health/ PMTCT New 1 st line drugs for adults, kids Altered second line Expedited referral with timelines Decreased monitoring TB Nurse initiation focus

17. Therapy for Early HIV Infection 200 500 < 200 350 CD4 Count (cell/mm 3 ) Symptomatic (Stages 3 & 4) Symptomatic (Stages 3 & 4) Asymptomatic (Stages 1 & 2) Asymptomatic (Stages 1 & 2) Clinical Symptoms

18. 164 187 102 181 200 192 87 239 163 97 134 179 97 100 125 123 86 122 103 53 157206 95 72  Review of data from 2003-2005 from 176 sites in 42 countries (N = 33,008) When Is Antiretroviral Therapy Started? Egger M, et al. CROI 2007. Abstract 62.

19. Children All children less than 1 year of age Children 1 – 5 years with clinical stage 3 or 4 or CD4 ≤ 25 % or absolute CD4 count < 750 cells/µl Children ≥ 6 years to 15yrs with clinical stage 3 or 4 or CD4 < 350 cells/µl. Huge implications for PCR screening!

20. MDR and XDR?

21. Treatment as prevention Prevention programmes results very disappointing Can reducing the viral load earlier have a public health impact? Convenient convergence!

22. Essentially, treatment IS prevention

23. 1 st line adults All new patients needing treatment, including pregnant women - TDF + 3TC/FTC +EFV/NVP Contraindication to TDF: renal disease AZT+ 3TC +EFV/NVP For those on existing d4T, remain, but vigilance urged

24. ddI d4T AZT 3TC 2 Nukes Non-nuke Efavirenz/ nevirapine Protease Kaletra Failure – VL>5000 Toxic!

25. Who is still taking d4T? Marlink R et al, IAC 2008 (WEAXO106) Westreich DJ, et al, Tuberculosis treatment and risk of stavudine substitution in first-line antiretroviral therapy, Clin Infect Dis. 2009 Jun 1;48(11):1617-23 Side effects potentiated by TB Rx

26. Major issue: PMTCT Complex regimens – being updated

27. What can stop us? Human resources Budget and treasury Beaurocracy and legislation

28. Context of care

29. Challenges

30. The difference? What we want INH CTX Regular monitoring Pap smears, fertility planning ‘Wellness’ – ‘prevention for positives’ (no weekend work, patient in clinic when suits us, keep their appointments) What patients want Being valued No queues Same health care worker Tablets that work Confidentiality Files and blood tests that don’t go missing Information that is appropriate Grants! Appointments, hours that don’t impact on work

31. The biggest challenge to our programmes is NOT safe or effective drugs or HIV testing – it is retention in care after HIV diagnosis

32. 1 st prize is a bulletproof 1 st line ARV regimen Tolerability > forgiveness (NNRTI vs PI) BUT – presupposes good support and adherence 2-3% migration to 2 nd line – accumulating body of patients Long haul – probably 50% of patients need minimal support

33. FDCs More for pharmacists than patients! Packaging and colours would be great

34. Issues around paediatrics The least “system proofed” group Try to harmonise with adults Weight of liquid formulations – score tablets, pay attention to ‘crushability’

35. OI drug needs Amphotericin B Macrolides - MAC Gancyclovir – CMV, possibly for other illnesses MDR treatment (Rifabutin)

36. PoC technologies? Proliferation of technologies with parallel lab system - ?justified in an HIV silo ?toxicity monitoring required Gene Xpert Viral load ?CD, ?Resistance ?POC rapid HIV test re-evaluation Sober reflection on the tech requirements

37. Summary of big ‘short term’ treatment and systems gaps? Earlier diagnosis and retention Bigger emphasis on more sophisticated adherence, esp toxicity management – preserve 1 st line Better packaging of drugs, FDCs New drugs for toxicity OI drugs Better and faster diagnosis of TB, VL; Reassess rapid HIV Simpler guidelines, align paeds and adult guidelines Expansion of who gives ART

38. HIV has showed what we can do Opportunity to fix the whole health care system now Heed our marching orders for 2012!

39. The End