1. Washington D.C., USA, 22-27 July 2012www.aids2012.org Summary of Track C: Epidemiology and Prevention Science Audrey Pettifor, UNC Christopher Hurt, UNC Sheri Lippman, CAPS/UCSF Albert Liu, SFDPH Sinead Delany-Moretlwe, WRHI Nora Rosenberg, UNC

2. Washington D.C., USA, 22-27 July 2012www.aids2012.org The Track C Team

3. Washington D.C., USA, 22-27 July 2012www.aids2012.org Key Themes and Overview We have effective tools Given limited resources, how do we deliver interventions to maximize efficiency and effectiveness so we can “Get to Zero”. –Who to target? Don’t know how interventions work in some populations (IDU) –What intervention(s) to use? What combination? –How to deliver to achieve maximum coverage and impact?

4. Washington D.C., USA, 22-27 July 2012www.aids2012.org WHO TO TARGET?

5. Washington D.C., USA, 22-27 July 2012www.aids2012.org

6. Washington D.C., USA, 22-27 July 2012www.aids2012.org

7. Washington D.C., USA, 22-27 July 2012www.aids2012.org (Prejean et al., 2011) MSM

8. Most people living with HIV will live where the wealth is concentrated Source: McKinsey Institute, UNAIDS 2012 2 of every 3 people living with HIV will be living in urban areas by 2030 600 big cities in the world in 2025: 25% of the population 60% of the global wealth Schwartlander.

9. Washington D.C., USA, 22-27 July 2012www.aids2012.org Populations at high risk within generalized epidemics MSM IDU Sex Workers Adolescents Aging Populations Transgender Persons Discordant Couples

10. Washington D.C., USA, 22-27 July 2012www.aids2012.org 4.8 million young people aged 15 – 24 years are living with HIV. 3 million (two out of every three) are girls Note: Global summary in title from UNAIDS, Together We Will End AIDS, 2012

11. Washington D.C., USA, 22-27 July 2012www.aids2012.org Map of HIV prevalence among female sex workers in low-income and middle- income countries, 2007-2011 Pooled Odds Ratio for HIV infection among female sex workers compared to other women of reproductive age –13.5 (95% CI 10.0-18.1) Baral/Kerrigan et al. THAC0501

12. Washington D.C., USA, 22-27 July 2012www.aids2012.org New cross-sectional measures of incidence > 200 cells / ul < 1.0 OD-n > 400 copies / ml < 80% Classified as recently infected CD4 cell count BED CEIA Avidity HIV viral load ≤ 200 cells / ul ≥ 1.0 OD-n ≥ 80% ≤ 400 copies/ ml Stop Development of assays (antibody and molecular or “HIV diversity assays”) Statistical modeling approaches Hybrids (lab + modeling) Incidence estimates obtained using the multi-assay algorithm O. Laeyendecker MOAC0203

13. Washington D.C., USA, 22-27 July 2012www.aids2012.org What is the right intervention(s) to use for the population(s) targeted and how do we achieve maximal impact?

14. Washington D.C., USA, 22-27 July 2012www.aids2012.org Behavioural Intervention HIV Counselling and Testing Coates T, Lancet 2000 Male & female condoms Treatment of STIs Grosskurth H, Lancet 2000 Male circumcision Auvert B, PloS Med 2005 Gray R, Lancet 2007 Bailey R, Lancet 2007 HIV PREVENTION combined interventions PMTCT Harm Reducation/Needl e exchange Structural /Social

15. Washington D.C., USA, 22-27 July 2012www.aids2012.org The effects of MC are sustained Time-varying Circumcision status Conventional Cox Model Unadjusted Conventional Cox Model Adjusted for Time- Varying Factors Cox Regression with Weights from Marginal Structural Modeling Circumcised (vs. uncircumcised) 0.38 [0.26 – 0.55] p<0.001 0.46 [0.31 – 0.69] p=0.001 0.35 [0.24 – 0.51] p<0.001 The protective effect of MMC was sustained at 65% 66 months post intervention Bailey R. TUAC0402

16. Washington D.C., USA, 22-27 July 2012www.aids2012.org Option B+ Benefits Source: UNICEF/BLC Discussion Paper and Methodology - Business Case for Options B/B+, 2012

17. Washington D.C., USA, 22-27 July 2012www.aids2012.org Harm reduction Harm reduction is working. In Amsterdam unsafe injections down and incidence declining(Grady MOAC0401) In Vietnam, IDUs account for 75% of all new infections. RCT of sexual risk reduction and needle- sharing intervention, needle sharing decreased from 14% at baseline to 3% at 3 months, and exhibited a durable effect (Go THAC0404). Modeling results of combination IDU interventions in particular high coverage sterile syringe distribution (Marshall FRLBC05)

18. Washington D.C., USA, 22-27 July 2012www.aids2012.org Treatment as Prevention Mathematical models can help guide decision-making (Granich, Kessler, Stover, Gweshe). Targeting all HIV-infected persons is always the most effective strategy The challenge will be determining which populations to target in the short-term given limited resources: –What CD4 level? (200-350? 350-500? >500?) –Which patients? (pregnant women? discordant couples? TB patients? IDUs? all?) This will depend on the epidemic context, current service delivery environment, and resources available.

19. HIV and STI Department, Health Protection Agency - Colindale HIV and AIDS Reporting System Why is HIV transmission continuing? And… in 2010 only 15-25% of MSM had an HIV test A Brown. THAC0201

20. Washington D.C., USA, 22-27 July 2012www.aids2012.org Expanding Testing Home based testing works (Carballo-Dieguez TUPDC0304) In South Africa by June 2011 a record 13,269,746 HIV tests were conducted. 16% tested positive of whom 48% had CD4 counts above 350 (Mbengashe THPDE0304) Peer testing of IDU in Thailand (Ti THAC0405)

21. Washington D.C., USA, 22-27 July 2012www.aids2012.org The treatment cascade: keeping people in care Success in finding those lost to care in NYC using programs to trace patients out of care (Udeagu MOPDC0306) Programs with tracing had lower LTFU, mortality and higher retention (McMahan MOAC0302) Community distribution of ART in Tanzania, Uganda and Zambia reduced LTFU (Koole MOAC0305)

22. Washington D.C., USA, 22-27 July 2012www.aids2012.org PrEP (like ART) works when taken % of blood samples with tenofovir detected HIV protection efficacy in randomized comparison Partners PrEP FTC/TDF arm 81%75% TDF279%62% iPrEx51%44% FEM-PrEP26%6% There is a clear dose-response between evidence of PrEP use & efficacy Baeten et al N Engl Med 2012 Grant et al N Engl J Med 2010 Van Damme et al N Engl J Med 2012 Thigpen et al N Engl J Med 2012 Mugo TUPL0102

23. Washington D.C., USA, 22-27 July 2012www.aids2012.org Why do we need PrEP demonstration projects? Will MSM want PrEP? How will MSM use PrEP? How will sexual practices change? Where are PrEP delivery systems best located? Will PrEP be safe in the “real world”? Cohen AIDS 2012

24. Washington D.C., USA, 22-27 July 2012www.aids2012.org PrEP knowledge, acceptability, and potential for risk compensation Author/PopulationYearPrEP Knowledge PrEP Acceptability Risk compensation? Metsch et al 653 MSM in Miami, DC 201115% Miami 30% DC 48% Miami 61% DC -- Duffus et al 89 seronegative partners in SD couple in South Carolina (74% heterosexual) 2010- 2011 --94%26% would be more likely to have unprotected sex with HIV+ partner, 27% reported would be difficult to take a daily pill Krakower et al. Internet-based survey of 5035 MSM in North America Dec 2010- Jan 2011 19%50%A substantial minority of MSM anticipate risk compensation for insertive (20%) or receptive (14%) anal sex while using PrEP Yang et al 238 MSM and TG men in Northern Thailand 201266%41% for MSM 37% for TGs --

25. The HIV Investment Framework Reduce Risk Reduce likelihood of transmission Reduce mortality and morbidity  Condoms  Male circumcision  PMTCT  Treatment  Key populations  Behavior change BASIC PROGRAMME ACTIVITIES CRITICAL ENABLERS SYNERGIES Adapted from: Schwartlander B, et al. The Lancet, 377 (9782), 2011

26. Diagnosed HIV+ OR, 3.00 (2.06-4.40) Undiagnosed HIV OR, 6.38 (4.33-9.39) Health insurance coverage OR,0.47 (0.29-0.77) >200 CD4 cells/mm 3 before ART initiation OR, 0.40 (0.26-0.62) ART adherence OR, 0.50 (0.33-0.76) HIV suppression OR, 0.51 (0.31-0.83) ART utilization/ access OR, 0.56 (0.41-0.76) HIV Detection Viral Suppression Healthcare visits OR, 0.61 (0.42-0.90) Lower income (<$20k) OR, 3.42 (1.94-6.01) (Millett, 2012) STRUCTURAL FACTORS AFFECT RETENTION IN CARE

27. Cumulative impacts of parental HIV/AIDS, abuse and hunger on child transactional sex Cluver. WEAC0102

28. Modeling Community Empowerment Interventions on Infections averted in FSW Combined ART and empowerment intervention may avert 16 - 40% of infections among sex workers across epidemics, assuming equal access to HIV testing and treatment Empowerment intervention could enable ART access among sex workers through a community-based outreach and mobilization approach Cumulative infections averted among FSWs and adults with scale-up of empowerment (2012-16) A. Wirtz THAC0502

29. Behavioural Intervention HIV Counselling and Testing Coates T, Lancet 2000 STRUCTURAL Male & female condoms Treatment of STIs Grosskurth H, Lancet 2000 Male circumcision Auvert B, PloS Med 2005 Gray R, Lancet 2007 Bailey R, Lancet 2007 Treatment for prevention Donnell D, Lancet 2010 Cohen M, NEJM 2011 Microbicides for women Abdool Karim Q, Science 2010 Grant R, NEJM 2010 (MSM) Baeten J, NEJM 2012 (couples) Thigpen, NEJM, 2012 (Heterosexuals) Oral pre-exposure prophylaxis Post Exposure prophylaxis (PEP) Scheckter M, 2002 HIV PREVENTION combined interventions Mugo TUPL0102 PMTCT Harm Reduction/Needle exchange