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Stopping HIV: what next? Brian Williams South African Centre for Epidemiological Modelling and Analysis http://public.me.com/williamsbg 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. 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 Papers in peer-reviewed journals Papers per year 5000 4000 3000 100k papers ~ $20 billion 2000 1000 0 1980 1985 1990 1995 2000 2005 2010 PubMed: HIV & AIDS Everyone is trying to help Bill Gates George Bush Charlize Theron Carla Bruni Bill Clinton Bob Geldoff Richard Gere Funding 50 Projected need US$ billions 40 30 “… the White House estimates the cost of [the] 30,000-troop surge would be about $30 billion per year” (Forbes.com 2/12/2009) Apollo $145 billion 20 10 Previous funding 0 1980 1990 2000 Year 2010 2020 Cohen J. HIV/AIDS. The great funding surge. Science. 2008;321:512-9 and UNAIDS Methods of control Behavioural Condoms Have fewer partners Delay sexual debut Avoid inter-generational sex Social Mobilize communities Reduce stigma Support sex workers Education and awareness Empower women Deal with migration Biomedical Treat STIs Microbicides Vaccines Male circumcision ART 40 Impact on HIV in the world Prevalence (M) 30 20 $150 billion 25 years 100k papers Great and the good 10 0 1980 1985 1990 1995 2000 2005 2010 1985 1990 1995 2000 2005 2010 Deaths (M/yr) 2 1 0 1980 www.unaids.org Methods of control Behavioural Condoms Have fewer partners Delay sexual debut Avoid inter-generational sex Social Mobilize communities Reduce stigma Support sex workers Education and awareness Empower women Deal with migration Biomedical Treat STIs Microbicides Vaccines Male circumcision ART 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 But: does ART really cut transmission? Relative infectivity on ART 0.10 0.10 0.08 0.08 0.06 0.06 0.04 0.04 0.02 0.02 0.00 0.00 2.5 33 4 4.5 5.5 4 55 66 Log10(reduction in viral load) 3.5 6.5 Wawer, JID, 2005; Fideli, ARHR, 2001. Mort. 0.010 0.05 0.00 1980 0.20 Off ART 2020 0.20 On ART 0.020 Prevalence 0.10 0.010 0.05 0.000 2000 0.00 1980 2040 0.15 0.00 1980 2020 Prevalence 0.010 0.05 0.000 2000 0.10 2040 0.000 2000 Off ART 2020 2040 On ART 0.020 0.15 0.10 0.010 0.05 0.00 1980 Incidence and mortality/yr 0.10 0.020 0.000 2000 2020 Mortality HIV in South Africa: test and treat immediately 2040 Incidence and mortality/yr Inc. Incidence 0.15 Prevalence 0.020 Prevalence Prevalence 0.15 0.20 Incidence and mortality/yr Base line Prev. Incidence and mortality/yr 0.20 Current strategy Universal access starting at CD4 = 200/µL Mort. 0.010 0.05 0.00 1980 0.20 Off ART 2020 0.20 On ART 0.020 Prevalence 0.10 0.010 0.05 0.000 2000 0.00 1980 2040 0.15 0.00 1980 2020 Prevalence 0.010 0.05 0.000 2000 0.10 2040 0.000 2000 Off ART 2020 2040 On ART 0.020 0.15 0.10 0.010 0.05 0.00 1980 Incidence and mortality/yr 0.10 0.020 0.000 2000 2020 Mortality HIV in South Africa: test and treat at 200/mL 2040 Incidence and mortality/yr Inc. Incidence 0.15 Prevalence 0.020 Prevalence Prevalence 0.15 0.20 Incidence and mortality/yr Base line Prev. Incidence and mortality/yr 0.20 David Ho: 1995 0.05 0.00 1980 0.20 0.010 9 M deaths Off ART 2020 0.20 On ART 0.020 0.10 0.010 0.05 0.000 2000 2020 Prevalence 0.010 0.00 1980 2040 0.15 0.00 1980 0.10 0.05 0.000 2000 2040 0.020 0.000 2000 Off ART 2020 2040 On ART 0.020 0.15 0.10 0.062 M deaths 0.010 0.05 0.00 1980 Incidence and mortality/yr Mort. Prevalence 0.10 Incidence 0.15 Prevalence Prevalence Inc. Incidence and mortality/yr 0.020 0.15 Prevalence 0.20 0.000 2000 2020 2040 Mortality HIV in South Africa: test and treat immediately in 1998 Incidence and mortality/yr Base line Prev. Incidence and mortality/yr 0.20 Assuming that this works what are the possible problems? • • • • Cost Side effects Resistance Acceptability US$ Billions/yr What will it all cost? 8 6 Universal testing 4 1% current GDP < 350/mL 2 0 2000 2010 2020 2030 2040 2050 Year Funding availability and needs Blue and brown: 17% of current and projected global funding (UNAIDS) Green: Universal testing; Red: < 350/µL 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 10 US$ Billions/yr 5 0 2000 -5 2010 2020 2030 2040 2050 2% current GDP -10 4% current GDP -15 -20 -25 Net costs/savings Blue and brown: 17% of current and projected global funding (UNAIDS) Green: Universal testing; Red: < 350/µL What about side effects? NRTI NNRTI PI FI NRTI NNRTI PI FI Drug resistance Acquired Transmitted 0.20 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.” Prevalence Between 1% and 5% per year 0.15 0.10 0.05 0.00 1996 1998 2000 2002 2004 Drug resistance (all forms) Treatment naïve patients in the UK Dunn, AIDS, 2007 Acceptability/Delivery Navneet Garg | Global Business Manager | Vestergaard Frandse In Kenya: 41,040 people tested in 1 week 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 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… 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. 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 Thank you