Combination HIV Prevention

Transcription

1 Combination HIV Prevention Timothy Mastro, MD, FACP, DTM&H FHI 360, Durham, North Carolina, USA 7 th INTEREST Workshop, Dakar, Senegal 15 May 2013

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3 Outline What Works for HIV Prevention? Highly Active HIV Prevention Game Changers Can we really end AIDS? Combination HIV Prevention 2013 The Way Forward 3

4 What works for HIV prevention? Knowledge of HIV status Behavioral interventions Clean injection equipment for IDUs Blood supply screening Condoms PMTCT Treatment of STIs Structural interventions Male circumcision ART - TasP Medication assisted therapy for drug users ARV PrEP 4

5 Highly Active HIV Prevention Biomedical Interventions Structural Interventions Highly Active HIV Prevention HIV Testing & Linkage to Care Community- Level Interventions Individual & Small Group Interventions Tom Coates, 2008

6 The End of AIDS? An AIDS free generation is within our reach. February 12, 2013

7 HIV Suppression Stops Transmission 96% HPTN 052: If an HIV-infected person adheres to ART, the risk of transmitting the virus is reduced by 96% UNAIDS 2011 AIDS at 30 SMARTER, FASTER, BETTER CAMPAIGN HPTN 052 is a game changer Michel Sidibe, Executive Director of UNAIDS 7

8 HPTN 052 Bruce Alberts, Editor of Science explains the choice of this work The results have galvanized efforts to end the world s AIDS epidemic in a way that would have been inconceivable even a year ago 8

9 The Prevention Science Revolution We finally have scientifically validated prevention modalities that clearly work, suggesting that ending the pandemic is feasible. Anthony S. Fauci Science 2011;333:13.

10 Successful HIV Prevention Trials Study Prime Boost vaccine (Thai RV144, 2009) 1% tenofovir gel (CAPRISA 004, 2010) TDF/FTC oral PrEP (iprex, 2010) Medical male circumcision (x3) (Orange Farm, 2005; Rakai, Kisumu, 2007) TDF/FTC oral PrEP (TDF2, CDC, 2011) TDF oral PrEP (Partners PrEP, 2011) TDF/FTC oral PrEP (Partners PrEP, 2011) Immediate ART for HIV positive partners (HPTN 052, 2011) 0% % Efficacy Effect size (CI) 31% (1, 51) 39% (6, 60) 44% (15, 63) 57% (42, 68) 63% (22, 83) 62% (34, 78) 73% (49, 85) 96% (82, 99) 10

11 Successful HIV Prevention Trials Study Prime Boost vaccine (Thai RV144, 2009) 1% tenofovir gel (CAPRISA 004, 2010) TDF/FTC oral PrEP (iprex, 2010) Medical male circumcision (x3) (Orange Farm, 2005; Rakai, Kisumu, 2007) TDF/FTC oral PrEP (TDF2, CDC, 2011) TDF oral PrEP (Partners PrEP, 2011) TDF/FTC oral PrEP (Partners PrEP, 2011) (VOICE, 2011) (VOICE, 2011) (FEM PrEP, 2011; VOICE, 2013) Immediate ART for HIV positive partners (HPTN 052, 2011) 0% % Efficacy Effect size (CI) 31% (1, 51) 0-39% ( 0, 60) 44% (15, 63) 57% (42, 68) 63% (22, 83) 0 62% ( 0, 78) 0 73% ( 0, 85) 96% (82, 99) 11

12 Four Prevention Opportunities Cohen et al, JCI, 2008 Cohen IAS 2008 UNEXPOSED EXPOSED EXPOSED INFECTED (precoital/coital) (postcoital) Behavioral, Structural Vaccines ART PrEP Microbicides Vaccines ART PEP Treatment Of HIV Reduced Infectivity Structural Circumcision Condoms YEARS HOURS 72h YEARS 12

13 Combination HIV Prevention 13

14 Guidance on Combination HIV Prevention UNAIDS, 2010 PEPFAR,

15 Core Elements of Combination Prevention in Africa Knowledge of HIV status Behavioral interventions Clean injection equipment for IDUs Blood supply screening Condoms PMTCT Treatment of STIs Structural interventions Male circumcision ART - TasP Medication assisted therapy for drug users ARV PrEP 15

16 What about PrEP? Summary of PrEP Trials Tenofovir gel safe & effective in CAPRISA 004 (BAT 24 dosing) But, not effective in VOICE (daily dosing) TDF/FTC (daily) effective and well tolerated: For MSM in iprex For hetero men & women in CDC TDF2 and Partners PrEP (also showed TDF effective) But, not effective for women in FEM PrEP and VOICE (low adherence) 16

17 Summary of PrEP Trials, cont TDF/FTC and HIV resistance No FTC resistance Limited tenofovir resistance Associated with started PrEP in persons with acute HIV infection (HIV seronegative) Risk compensation was not seen in trials Need to better understand adherence Awaiting results: CDC Bangkok Tenofovir Study among IDU FACTS 001 study of tenofovir gel in South Africa 17

18 Defining Combination Prevention: Ongoing trials in sub Saharan Africa NIH s Methods for Prevention Packages Program MP3 I NIH s Methods for Prevention Packages Program MP3 II PEPFAR-funded effectiveness trials South Africa and Uganda Methods for Prevention Packages Program Home-based HIV testing and targeted referrals for VMMC, ART, STI treatment, couples counseling and oral PrEP plus topical PrEP (if effective) Botswana An HIV Prevention Package for Mochudi Behavioral interventions: VCT, partner notification, concurrency reduction, VMMC, condoms and ART for those with high viral load Kenya Gender-Specific Combination HIV Prevention for Youth in High-Burden Settings Gender-specific HIV packages for male and female youth delivered using community-based mobile health teams Tanzania Johns Hopkins University with USAID funding Evaluation of the impact on HIV incidence of expanding population coverage of an integrated set of HIV prevention interventions Malawi Acute Infection in Heterosexuals Standard vs. enhanced counseling vs. behavioral intervention plus 12-week ART to reduce viral load South Africa and Zambia PopART/HPTN 071 A strategy linking household-based HIV testing to universal community-based HIV treatment Botswana Harvard School of Public Health with US CDC funding Evaluation of the impact on HIV incidence of expanding population coverage of an integrated set of HIV prevention interventions In addition to the trials pictured, there are also evaluations ongoing in Europe, North and South America. For a complete list, visit avac.org/pxrd. AVAC Report 2012: Achieving the End One year and counting. Zambia and South Africa Comprehensive HIV Prevention Package for MSM in Southern Africa Package of behavioral, biomedical and community-level interventions Lesotho Enhance Prevention in Couples Behavioral counseling, ART for prevention (CD4<500) plus couples counseling, VMMC South Africa CHAMPS: Choices for Adolescent Methods of Prevention in South Africa Potentially PrEP, microbicides, HCT and circumcision plus messaging and social marketing around these approaches

19 Treatment as Prevention Major Studies in Africa ANRS TasP Study in South Africa (Newell) PEPFAR Combination Prevention Trials: NIH HPTN 071 South Africa, Zambia (Hayes) CDC BOTSWANA (Essex) USAID JHU Tanzania See: 19

20 HPTN 071 (PopART) Treatment for prevention: a new paradigm for HIV control

21 PopART: Population effect of universal testing and immediate ART therapy to Reduce HIV Transmission

22 HPTN 071 / PopART Sponsor Funders: through the

23 Hypothesis Universal voluntary HIV testing with appropriate combination prevention offered to all those testing HIV negative - in addition to immediate ART for all those testing HIV positive - will have a substantial impact on HIV incidence at population level

24 The PopART Intervention Package Universal voluntary HIV testing delivered annually through door-to-door, home-based testing Linkage to care at the local health center for those testing HIV positive Immediate ART offered at the local health center to those testing HIV positive Promoting voluntary male circumcision to men who test HIV negative Strengthening and promoting PMTCT services Syndromic STI treatment at clinic Counseling and condom provision in the community Community HIV Providers (CHiPs) to deliver testing, counseling, linkage to care and treatment support in the community

25 Trial Design: three-arm, two-country, cluster-randomized Arm A (7 sites) Full PopART Arm B (7 sites) PopART, but CD4<350 Arm C (7 sites) Standard of Care 21 clusters (communities): 12 in Zambia, 9 in South Africa Average of ~50,000 in each cluster, of which 50% adults Incidence measured in Population Cohort: 2,500 adults in each cluster, followed up after 1, 2 and 3 years

26 Trial Design: Three Arm, Two Country Cluster Randomized C B A Zambia B A C A C B Avg. ~25,000 adults A Enroll 2,500 C B B A C A C B A C B South Africa

27 Study Locations: 12 communities in Zambia Zambia 9 communities in the Western Cape of South Africa South Africa

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29 Objectives Primary Objective To measure the impact of the PopART intervention in reducing HIV incidence Measured in a cohort of 52,500 adults over 3 years

30 Objectives Secondary Objectives Uptake of intervention components Retention in HIV care Sexual risk behavior HIV-related stigma HIV disease progression and death TB case notification rate HSV-2 incidence ART Toxicity ART adherence and viral suppression Community viral load ART drug resistance

31 Moving Forward 31

32 Is There an HIV Prevention Tipping Point? What level of coverage is needed to stop transmission? HIV testing ART Male circumcision (VMMC) Is this the tipping point? When the number of HIV infected people starting ART is greater than the number of new HIV infections? 32

33 ART Coverage and HIV Incidence, KwaZulu Natal, South Africa Africa Centre, Univ of KwaZulu Natal Africa s largest population based cohort study; >16,000 HIV negative people followed, HIV incidence decline associated with increased ART coverage Communities with 30 40% ART coverage had 38% lower HIV incidence than communities with <10% ART coverage Tanser F, Science, Feb

34 The Continuum of HIV Care, United States M 942 K K % 77% 480 K 427 K 328 K 20 51% 89% 0 HIV Infected HIV Diagnosed Linked to HIV Care Retained in HIV Care Engagement in HIV Care On ART 77% Suppressed Viral Load ( 200 copies/ml) 850,000 with HIV do not have virus under control (72%) Source: MMWR (2011)

35 The Continuum of HIV Care, Sub Saharan Africa 23.5M 11.8M 50% 8.3M 70% 4.1M 50% 3.3M 80% 2.0M 60% Engagement in HIV Care >20 Million with HIV do not have virus under control (86%) Sources: FHI 360 adapted from UNAIDS (2012)

36 Coverage of HIV Prevention Tools Low Middle Income Countries, Estimates of Coverage Unmet Need for HIV Prevention HIV testing 5% 20% 39% 50% 61% Condom Use 9% 15% 20% 22% 78% Male Circumcision 5% 10% 90% Antiretrovirals for Adults 11% 25% 47% 54% 46% Antiretrovirals for PMTCT 9% 32% 53% 57% 43% Contraception for PMTCT 14% 20% 28% 33% 67% 0% 20% 40% 60% 80% 100% / Unmet HIV Prevention Need Source: Adapted from UNAIDS/WHO/DHS, 2012

37 HIV Prevention in 2013 We have powerful new tools in the toolkit, especially TasP and medical male circumcision We need to learn now best to use these new tools Adequate levels of coverage will be essential Need to identify cost effective strategies Ongoing studies and efforts will determine if we can turn back the HIV epidemic 37

38 The Economist June 4,

39 Acknowledgments Myron Cohen Wafaa El Sadr Quarraisha Abdool Karim Salim Abdool Karim Ward Cates Sten Vermund Cate Hankins Nirupama Sista Sam Griffiths Richard Hayes Sarah Fidler Nulda Beyers Helen Ayles Mitchell Warren Amy Corneli Jen Deese Lut Van Damme Maya Tremelling