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Prevention Today: What ’ s the Right Mix? Scientific Overview

Prevention Today: What ’ s the Right Mix? Scientific Overview. Catherine Hankins BA MD MSc FRCPC Deputy Director, Science Amsterdam Institute for Global Health and Development Honorary Professor London School of Hygiene and Tropical Medicine. AIDS 2012: Turning the Tide Together

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Prevention Today: What ’ s the Right Mix? Scientific Overview

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  1. Prevention Today: What’s the Right Mix? Scientific Overview Catherine Hankins BA MD MSc FRCPC Deputy Director, Science Amsterdam Institute for Global Health and Development Honorary Professor London School of Hygiene and Tropical Medicine AIDS 2012: Turning the Tide Together 19th International AIDS Conference Washington, DC, USA

  2. Prevention Today: What’s the Right Mix? Scientific Overview • Investment choices • Combination prevention of sexual transmission • Overview of trial results: what works, what doesn’t, what’s next • Know your epidemic/know your response

  3. AIDS investment framework CRITICAL ENABLERS BASIC PROGRAMME ACTIVITIES OBJECTIVES Keypopulations Children & mothers • Social enablers • Political commitment & advocacy • Laws, policies & practices • Community mobilization • Stigma reduction • Mass media • Local responses, to change risk environment Stopping new infections Behaviour change Condoms Keeping people alive • Programme enablers • Community-centered design & delivery • Programme communication • Management & incentives • Production & distribution • Research & innovation Care & treatment Male circumcision SYNERGIES WITH DEVELOPMENT SECTORS Social protection; Education; Legal Reform; Gender equality; Poverty reduction; Gender-based violence; Health systems (incl. treatment of STIs, blood safety); Community systems; Employer practices.

  4. Combination Prevention: Basic Attributes • Tailoredto national and local needs and contexts • Combinesbiomedical, behavioural and structuralelements—to reduce both immediate risks and underlying vulnerabilities • Fully engagesaffected communities, promoting human rights and gender equality • Operates synergisticallyon multiple levels—individual, family and society • Invests in decentralized and community responses and enhances coordination and management • Flexible—adapts to changing epidemic patterns and can rapidly deploy innovations Adapted from UNAIDS 2010

  5. Opportunities for Preventing Sexually Transmitted HIV Infection Unexposed Exposed (precoital/coital) Exposed (postcoital) Infected Behavioural, structural Male circumcision, Vaccine, Condoms Topical microbicides, oral PrEP, Vaccine, Condoms Vaccine, PEP Treatment of HIV, reduced infectivity Years Hours 72h – 28d Years Cohen et al. J. Clin. Invest. 118:4, 2008

  6. Biomedical and Behavioural Prevention Grant NEJM 2010 Baeton NEJM 2012 Thigpen NEJM 2012 Behavioural change • Abstinence • Be faithful

  7. Male and Female Condoms Male condom effectiveness • Meta-analyses: Greater than 90% when used correctly and consistently (Condoms for HIV prevention in developing countries: a review of the scientific literature. UNAIDS 2003) • Cochrane Review: always vs. never: 80% reduction in incidence Female condoms: (Peters et al 2010) • price monopolies • 25 times price of male condom • WHO ambivalencere washing and reuse • lack of active promotion by UNAIDS: low demand • stock-outs • underproduction with no economies of scale • good acceptability with frustrated demand

  8. Risk ratio (95% CI) 0.42 (0.34,0.54) Observational studies South Africa 0.41 (0.24,0.69) Kenya 0.41 (0.24,0.70) Uganda 0.43 (0.24,0.75) 0.42 (0.31,0.57) p<0.0001 Overall (95% CI) 0.2 0.3 0.4 0.5 1 1.5 Risk ratio Scientific Evidence: Male Circumcision Reduces HIV Risk in men Favours male circumcision Favours lack of circumcision Weiss et al AIDS 2008: 22: 567-574

  9. Effect Persists 5 years Post-trial Follow-up Gray, Kigozi, Kong et al AIDS 2012; 26:609-15 Kisumu, Kenya 66% reduction over 4.5 years. Bailey et al Orange Farm, South Africa HIV incidence 65% lower among circumcised men. Lissouba et al BMC Inf Dis 2011

  10. Number and % Infections Averted to 2025 by Scale-up to 80% Coverage by 2015 Hankins, Forsythe, Njeuhmeli PLoS Med 2011

  11. On near horizon: Devices for adults Barone et al JAIDS 2011 (Kenya) Musau et al J Urol 2011 (Kenya) Bitega et al JAIDS 2012 (Rwanda) Shang Ring Alisklamp PrePEX

  12. Antiretroviral Drugs for HIV Prevention Antiretroviral therapy for HIV+ persons Reduce onward transmission • Prevent vertical transmission (through maternal treatment) • Prevent horizontal transmission: • T4P: treatment for prevention before CD4+ cells reach 350/uL (HPTN 052 – 96%) Antiretroviral prevention for HIV- persons Reduce HIV acquisition • Prevent vertical transmission (infant during breastfeeding • Pre-exposure prophylaxis to prevent horizontal transmission (MF; MM; FM)

  13. 96% Results of the HPTN052 trial announced on 12 May 2011 show that if an HIV-positive person adheres to an effective antiretroviral therapy regimen, the risk of transmitting the virus to their uninfected sexual partner can be reduced by 96% Starting at CD4 350-550 versus CD4 less than 250 Treatment for prevention is a game changer. Michel Sidibe Executive Director of UNAIDS

  14. CD4 Cell Count at ART Initiation Adapted from Vitoria et al, ICASA 2011

  15. Antiretroviral treatment coverage 2004-2011 Patients on treatment: Individual, geo-located adult patients actively on treatment in June (2004-2011) HIV-infected: Individual, geo-located, HIV-positive adults identified through population-based HIV surveillance data (2004-2011) Tanser et al CROI 2012

  16. Adjusted HIV Acquisition Hazard by ART Coverage Category: Hlabisa, South Africa Adjusted for age, sex, community-level HIV prevalence, urban vs. rural, marital status, >1 partner in last 12 months, and household wealth index Tanser et al CROI 2012

  17. Pre-exposure prophylaxis strategies Tenofovir/emtricitabine TDF/FTC Tenofovir (TDF) • iPrEx • Partners PrEP • TDF2 Topical PrEP: 1% tenofovir gel • CAPRISA 004 • Injectable PrEP: subcutaneous or intramuscular (Phase 1 trials)) ASPIRE and IPM trials Intermittent PrEP trials

  18. Pre-exposure Prophylaxis for Women as of July 2012

  19. Systemic Versus Topical Administration in Women

  20. Fem-PrEP: Adherence measurements Van Damme CROI 2012, LB32 More info NEJM 2012

  21. CAPRISA 004: Adherence is critical to efficacy against HIV • High (>80% gel adherence): n=336 (38%) 54% efficacy • Intermediate (50-80% adhere): n=181 (20%) 38% efficacy • Low (<50% gel adherence): n=367 (42%) 28% efficacy Abdool Karim et al, Science 2010

  22. Efficacy by as-treated analysis (data as of Nov 21, 2011) High (≥ 90% adherence; 49% of visits) 68% efficacy Intermediate (50-90% adherence; 33% of visits) 34% efficacy Low (< 50% adherence;18% of visits) 16% efficacy iPrEx: Adherence is Critical to Efficacy • 9% of seroconverters had • detectable drug at first HIV+ visit versus 51% of nonseroconverters • Grant et al, NEJM 2010

  23. Technological advances in virology CD4 binding site From discovering HIV in 1983 to high throughput screening for neutralizing antibodies From weeks of waiting for results to point of care testing

  24. Population-based studies of combination prevention Titel

  25. Population-based studies of combination prevention Courtesy El-Sadr. CROI 2012

  26. Clinical Trial Evidence: Prevention of Sexual HIV Transmission • Tekst • Tekst • Tekst • Tekst ü ü ü ü ü ü û û û û û û + ++ – – – +/– ++/– – 75% (55; 87) 62% (22; 83)

  27. The choice of the mix of prevention interventions is not always tailored to the structure of the epidemic Key pops

  28. CONTEXT Know your epidemic/know your response EPI REVIEW EVIDENCE RESOURCE REVIEW RESPONSE REVIEW CONSULTATION & REPROGRAMMING Hankins and De Zalduondo AIDS 2010

  29. With thanks to: • Helen Weiss • Myron Cohen • KiwangoAgot • Jared Beaton • Frank Tanser • SalimAbdoolKarim • Wafaa El-Sadr • Marco Vitoria • LutVan Damme • ConnnieCelum • Barbara de Zalduondo • EleanourGouws • Carl Dieffenbach • QuarraishaAbdoolKarim • Dawn Smith • Lynn Paxton • Bob Grant • Kevin O’Reilly • Emmanuel Njeuhmeli • Eddy Beck • ….and other colleagues

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