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. 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. 0.00 0.05 0.10 0.15 1830183518401845185018551860 Maternal mortality dismissed Only midwives in red clinic Semmelweiss Semmelweiss introduces hand washing in blue clinic Ignaz Philipp Semmelweiss (1818 –1865)

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

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

12. What about adolescents?

13. Age (years) Survival 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/  L, median age 11 yrs, 55% double orphans Ferrand CID (2007) 44:874 Two 16 year old children. The child on the right has been in a wheel chair with arthritis since the age of five.

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

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

17. Age (years) Prevalence of HIV Number of children 1995 2000 2005 2010 2015 2020 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=36814http://guideline.gov/content.aspx?id=36814

21. 20 40 Likelihood (%) of developing an AIDS related illness in 3 years Analysis of MACS data. DHHS 2000; IAS 2000; WHO 2002 5 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. 10 Young men Orange Farm 2000 Carpenter et al. JAMA (2000) 283: 381-390; DHHS (2000)http://guideline.gov/content.aspx?id=36814; WHO (2002) www.who.int

22. 20 40 Likelihood (%) of developing an AIDS related illness in 3 years Analysis of MACS data. DHHS 2000; IAS 2000; WHO 2002 5 90% eligible 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 10 Young men Orange Farm 2000 Carpenter et al. JAMA (2000) 283: 381-390; DHHS (2000)http://guideline.gov/content.aspx?id=36814; WHO (2002) www.who.int

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

24. 20 40 Likelihood (%) of developing an AIDS related illness in 3 years Analysis of MACS data. DHHS 2000; IAS 2000; WHO 2002 5 90% eligible 10% eligible 90% eligible The number eligible for treatment dropped from 90% to 10% 10 Young men Orange Farm 2000 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 patients when the CD4 count drops below 200/  L. … While beginning therapy before the CD4 cell count falls below 200/  L clearly provides clinical benefits, the actual point above 200/  L at which to 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] provides clinical 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. Red: Prevalence of HIV; Blue: number of people living with HIV in Can Tho, Vietnam Kato JAIDS (2013) in press. Risk group Size of group

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