Ending AIDS Past, Present and Yet to Come Brian Williams Newton Institute August 2013

1. Ending AIDS Past, Present and Yet to Come Brian Williams Newton Institute August 2013 Ask not what public health can do for epidemiology but what epidemiology can do for public health (With apologies)

2. The philosophers have only interpreted the world, in various ways; the point, however, is to change it. In France the controversy [about whether or not inoculation was a good thing] was brought to an end by the death of Louis XV T.W. Körner Marx, K. (1845) Theses on Feuerbach

3. A cautionary tale Where science and politics meet Chris Dye: Modelling is still not on the radar screen of public health

4. Semmelweiss introduces hand washing in blue clinic Only midwives in red clinic Semmelweiss Ignaz Philipp Semmelweiss (1818 –1865) 0.15 dismissed 0.10 Maternal mortality 0.05 0.00 1830 1835 1840 1845 1850 1855 1860 Medical students were doing autopsies before coming into the maternity wards but mid-wives were not. After 1839 students no longer came into the red ward and maternal mortality dropped. In 1848 he introduced hand-washing and mortality dropped in the blue wards. In 1849 he was fired for criticizing his superiors. In 1865 he died of septicaemia in an asylum.

5. A VERY brief history of HIV/AIDS

6. 1980s: Basic epidemiology established • Routes of transmission understood • Initial doubling time: 2 to 5 years • Survival: Weibull (2.25; 11 years) • Risk per sexual encounter: 0.001 • Other STIs enhance transmission • R0 ~ 7 • Diagnostic test developed • First anti-retroviral drug available

7. 1990s: Drugs, risk-groups and impact • Triple therapy available (very expensive) • IDU & MSM in developed countries; IDU & FSW in Asia; heterosexual in Africa • Nine worst affected countries in the world in southern Africa; North India 200x less than South Africa.

8. 2000s: Cheap drugs, lots of money, 3x5, what doesn’t work • Drug prices fall by 1000x • Behaviour change; condoms; STI treatment don’t really work • CD4: marker of progression • Viral load: marker of survival and infectiousness • Vertical transmission can be stopped

9. 2010s: What works • Male circumcision: 60% reduction • PreP: 40% reduction • ART reduces viral load from 100,000 to 10/mL. • ART cost US$100 p.a.; well tolerated; resistance falling.

10. David Ho 1995 What if…. …we had started to treat early and hard in 1995…..

11. Base line Incidence Prev. Inc. Mort. Mort. Off ARTOn ART Off ARTOn ART Prevalence Mortality HIV in South Africa: test and treat starting in 1995

12. What about adolescents?

13. Survival Age (years) Survival of children born with HIV in Africa Marston JAIDS (2005) 38: 219

14. Case study: 2006 32 adolescents presenting with HIV in Harare. Most were severely stunted and suffering from AIDS defining illnesses. Median CD4+ 100/mL, median age 11 yrs, 55% double orphans Two 16 year old children. The child on the right has been in a wheel chair with arthritis since the age of five. Ferrand CID (2007) 44:874

15. Survival against age at HIV seroconversion from the CASCADE study Proportion surviving Years since infection CASCADE Lancet (2000) 355: 1131-1137.

16. Combine the data on very young children with the data from the CASCADE study

17. 2015 Prevalence of HIV 2020 Number of children 2000 2010 1995 2005 Age (years) Predicted prevalence of HIV in South African children and the number of AIDS orphans being maintained on ART by the Catholic Bishops conference in 2007 Ferrand CID (2007) 44:874

18. Predicted and observed prevalence of HIV in adolescents in 2003 Ferrand CID (2007) 44:874

19. Treatment guidelines The effect of treatment guidelines on the number of people eligible for treatment: 2000-2002 DHHS; IAS; WHO DHHS (2000) http://guideline.gov/content.aspx?id=36814; Carpenter et al. JAMA (2000) 283: 381-390; World Health Organization, Geneva (2002)

20. Probability of developing an AIDS related illness in 3 years DHHS data from the MACS cohort, 2000 DHHS; USA (2000) http://guideline.gov/content.aspx?id=36814

21. Young men Orange Farm 2000 90% eligible DHHS 2000: All to the right and below the lines should start ART. The rest should not. In South Africa 90% of all HIV positive people were eligible for ART. 5 40 10 20 Likelihood (%) of developing an AIDS related illness in 3 years Analysis of MACS data. DHHS 2000; IAS 2000;WHO 2002 Carpenter et al. JAMA (2000) 283: 381-390; DHHS (2000)http://guideline.gov/content.aspx?id=36814; WHO (2002) www.who.int

22. Young men Orange Farm 2000 IAS 2000: All to the right and below the lines should start immediately. Between the lines consider treatment. Top left don’t start. In South Africa in 2000 90% of all HIV positive people were eligible for ART. 90% eligible 90% eligible 5 40 10 20 Likelihood (%) of developing an AIDS related illness in 3 years Analysis of MACS data. DHHS 2000; IAS 2000;WHO 2002 Carpenter et al. JAMA (2000) 283: 381-390; DHHS (2000)http://guideline.gov/content.aspx?id=36814; WHO (2002) www.who.int

23. Young men Orange Farm 2000 WHO 2002: Only those below the line should start ART. In South Africa10% of all HIV positive people were eligible for ART 5 40 10 20 10% eligible Likelihood (%) of developing an AIDS related illness in 3 years Analysis of MACS data. DHHS 2000; IAS 2000;WHO 2002 Carpenter et al. JAMA (2000) 283: 381-390; DHHS (2000)http://guideline.gov/content.aspx?id=36814; WHO (2002) www.who.int

24. Young men Orange Farm 2000 90% eligible 90% eligible The number eligible for treatment dropped from 90% to 10% 5 40 10 20 10% eligible Likelihood (%) of developing an AIDS related illness in 3 years Analysis of MACS data. DHHS 2000; IAS 2000;WHO 2002 Carpenter et al. JAMA (2000) 283: 381-390; DHHS (2000)http://guideline.gov/content.aspx?id=36814; WHO (2002) www.who.int

25. Rationale for 2002 guidelines [Only start treatment] in asymptomatic patientswhen the CD4 count drops below 200/mL. … While beginningtherapy before the CD4 cell count falls below 200/mL clearlyprovides clinical benefits, the actual point above 200/mL at whichto start therapy has not been definitively determined. WHO (2002). Scaling up Antiretroviral Therapy in Resource Limited Settings: Guidelines for a Public Health approach. Geneva, World Health Organization.

26. IAS (DHHS) guidelines 2012 All adults with HIV infection should be offered ART regardless of CD4 cell count, based on …data [showing] that all patients may benefit from ART …[and] that ART reduces the likelihood of HIV transmission [and] providesclinical benefits. Thompson et al. JAMA (2012) 308: 387-402.

27. Ending AIDS in Vietnam Can Tho Province

29. 0 Size of each group and sub-group HIV prevalence by risk group in Can Tho Province, Vietnam Kato JAIDS (2013) in press

30. Force infection to start in FSW HIV prevalence by risk group in Can Tho Province, Vietnam Kato JAIDS (2013) in press

31. Risk group Size of group Red: Prevalence of HIV; Blue: number of people living with HIV in Can Tho, Vietnam Kato JAIDS (2013) in press.

33. Current coverage CD4 350 (90%) Methadone (IDU); condoms (MSM) Annual testing, immediate treatment (80%)

34. The understanding that mathematical models brings is essential for good public health. But people and politicians make decisions for many reasons, most of which we don’t understand and may not even be aware of. We need to think carefully about how to persuade them of the value of our work and how to understand what it is that constrains their world and decisions.

35. Thank you