Stopping HIV: what next? Brian Williams

1. Stopping HIV: what next? Brian Williams South African Centre for Epidemiological Modelling and Analysis http://public.me.com/williamsbg

2. The scale of the epidemic Small pox AD 164-180 Killed 5 million in the Roman Empire Small pox 1520 Killed half of all the Aztecs Black Death (bubonic plague) 1347-1351 Killed 25 million in Europe Influenza 1918 Killed 20 million people HIV 1980 to … 40 million dead; 30 million infected; 20 million more in the next ten years.

3. The scientific response 1981: CDC reports five deaths 1983: Virus is identified at the Institut Pasteur 1985: The full genome of the virus is sequenced First ELISA test licensed 1987: AZT approved by the FDA 1996: Triple therapy available but costs $10,000/yr 2006: Cost of first line therapy reduced to $100/yr 2009: 22 drugs in 3 classes; 3 new classes under development

4. Papers in peer-reviewed journals Papers per year  100k papers ~ $20 billion PubMed: HIV & AIDS

5. Everyone is trying to help George Bush Bill Clinton Bill Gates Carla Bruni Charlize Theron Richard Gere Bob Geldoff

6. Funding Projected need Apollo $145 billion “… the White House estimates the cost of [the] 30,000-troop surge would be about $30 billion per year” (Forbes.com 2/12/2009) US$ billions Previous funding Cohen J. HIV/AIDS. The great funding surge. Science. 2008;321:512-9 and UNAIDS

7. Methods of control Behavioural Condoms Have fewer partners Delay sexual debut Avoid inter-generational sex Biomedical Treat STIs Microbicides Vaccines Male circumcision ART Social Mobilize communities Reduce stigma Support sex workers Education and awareness Empower women Deal with migration

8. Impact on HIV in the world $150 billion 25 years 100k papers Great and the good Prevalence (M) Deaths (M/yr) www.unaids.org

9. Methods of control Behavioural Condoms Have fewer partners Delay sexual debut Avoid inter-generational sex Biomedical Treat STIs Microbicides Vaccines Male circumcision ART Male circumcision ART Social Mobilize communities Reduce stigma Support sex workers Education and awareness Empower women Deal with migration

10. HIV… Initial doubling time in South Africa  1.5 years Each HIV-positive person infects one other person every 1.5 years (on average) Life expectancy after infection  10 years Each HIV positive person infects 10/1.5  7 people Testing people once a year, start ART immediately and assume that they are no longer infectious, we will cut transmission by 10 times and (eventually) eliminate HIV

11. But: does ART really cut transmission? 0.10 0.08 0.06 0.04 0.02 0.00 Relative infectivity on ART 3 4 5 6 Log10(reduction in viral load) Wawer, JID, 2005; Fideli, ARHR, 2001.

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

13. Current strategy Universal access starting at CD4 = 200/µL

14. Base line Incidence Off ARTOn ART Off ARTOn ART Prevalence Mortality Prev. Inc. Mort. HIV in South Africa: test and treat at 200/mL

15. David Ho: 1995

16. Base line Incidence 9 M deaths Off ARTOn ART Off ARTOn ART 0.062 M deaths Prevalence Mortality Prev. Inc. Mort. HIV in South Africa: test and treat immediately in 1998

17. Assuming that this works what are the possible problems? • Cost • Side effects • Resistance • Acceptability

18. US$ Billions/yr Universal testing 1% current GDP < 350/mL Funding availability and needs Blue and brown: 17% of current and projected global funding (UNAIDS) Green: Universal testing; Red: < 350/µL What will it all cost?

19. What is the cost of losing a life? Cost to the state  GNI/year x 30 years x Employment rate  US$ 6,000 x 30 x 0.6  US$ 100,000

20. US$ Billions/yr 2% current GDP 4% current GDP Net costs/savings Blue and brown: 17% of current and projected global funding (UNAIDS) Green: Universal testing; Red: < 350/µL

21. What about side effects? NRTI NNRTI PI FI

22. NRTI NNRTI PI FI

23. Transmitted Prevalence Drug resistance (all forms) Treatment naïve patients in the UK Dunn, AIDS, 2007 Drug resistance Acquired Between 1% and 5% per year Phillips, AIDS, 2005 Hoffman, CID, 2009 Garcia-Gasco, JAC, 2008 “The wider use of regimens that suppress viral concentration to below infectious levels is one of several plausible explanations for this finding.”

24. Acceptability/Delivery Navneet Garg | Global Business Manager | Vestergaard Frandsen In Kenya: 41,040 people tested in 1 week

25. Phase I: Pilot projects • Acceptability of testing • Acceptability of treatment • Compliance with treatment • Minimal side effects • Make sure that we do not create stigma • Check that we get viral-load suppression • Measure residual transmission • Check for viral rebound • Monitor drug resistance • Consider cost and delivery

26. Phase II: Randomized controlled trials or step-wise interventions Monitor all of the above outcomes but also measure changes in incidence of HIV and TB at a population level…

27. Phase III: Just do it But ensure that we build in the best possible monitoring and evaluation of all biomedical, behavioural and psycho-social consequences while using models to fully understand the dynamics of the impact.

28. If one is caught in a dark maze it is better to light a candle than to repeatedly walk into the walls. Those [who] continue to dismiss theoretical models, … seem concerned with only the darkness and not the maze. Ulanowicz 1988

29. Thank you