The potential and challenges of ARV-based HIV prevention: An overview Salim S Abdool Karim Director: CAPRISA Pro Vice-Chancellor (Research): University of KwaZulu-Natal Professor in Clinical Epidemiology, Columbia University Associate Member, Ragon Institute of MGH, MIT and Harvard Adjunct Professor of Medicine, Cornell University

Outline Clinical trial evidence for ARV-based prevention Challenges in implementing PrEP & TasP The need for PrEP & TasP to prevent HIV in vulnerable Key Populations Conclusion

Clinical trial evidence for ARV prophylaxis Effect size (CI) Prevention in IDUs Bangkok Tenofovir Study– daily oral Tenofovir (IDUs– Thailand) 49% (10; 72) ART for prevention HPTN052 Africa, Asia, Americas 96% (73; 99) Partners PrEP – daily Truvada (Discordant couples – Kenya, Uganda) 75% (55; 87) Partners PrEP – daily oral Tenofovir (Discordant couples – Kenya, Uganda) 67% (44; 81) TDF2 – daily Truvada (Heterosexuals men and women- Botswana) 62% (22; 84) iPrEx – daily Truvada (MSM - America’s, Thailand, South Africa) 44% (15; 63) Sexual transmission prevention CAPRISA 004 – coital Tenofovir gel (Women – South Africa) 39% (6; 60) MTN003/VOICE – daily Tenofovir gel (Women – South Africa, Uganda, Zimbabwe) 15% (-21; 40) FEMPrEP – daily Truvada (Women – Kenya, South Africa, Tanzania) 6% (-52; 41) MTN003/VOICE – daily Truvada (Women – South Africa, Uganda, Zimbabwe) -4% (-49; 27) MTN003/VOICE – daily Viread (Women - South Africa, Uganda, Zimbabwe) -49% (-129; 3) -130 -60 -40 -20 20 40 60 80 100 Effectiveness (%) Source: Adapted from Abdool Karim SS. Lancet 2013

In May 2011, HPTN 052 shows that ART prevents HIV transmission from infected partners in discordant couples 1763 discordant couples in Africa & America Effect on ART (HIV +ve) on HIV: 96% (CI: 73% - 99%)

ARV prophylaxis HIV PREVENTION Male circumcision Treatment of STIs Auvert B, PloS Med 2005 Gray R, Lancet 2007 Bailey R, Lancet 2007 Treatment of STIs Grosskurth H, Lancet 2000 Microbicides for women Abdool Karim Q, Science 2010 Female Condoms Male Condoms HIV PREVENTION Grant R, NEJM 2010 (MSM) Baeten J , 2011 (Couples) Thigpen M, 2011 (Heterosexuals) Choopanya K, 2013 (IDU) Oral pre-exposure prophylaxis HIV Counselling and Testing Coates T, Lancet 2000 Sweat M, Lancet 2011 Post Exposure prophylaxis (PEP) Scheckter M, 2002 Behavioural Intervention Abstinence Be Faithful Treatment for prevention Cohen M, NEJM 2011 Donnell D, Lancet 2010 Tanser F, Science 2013 Note: PMTCT, Screening transfusions, Harm reduction, Universal precautions, etc. have not been included – this is focused on reducing sexual transmission

July 2012: First antiretroviral approved for HIV prevention - Tenofovir + FTC

Interim Guidance for Clinicians Considering the Use of Preexposure Weekly / Vol. 61/No.31 August 10, 2012 Interim Guidance for Clinicians Considering the Use of Preexposure Prophylaxis for the Prevention of HIV Infection in Heterosexually Active Adults Source: CDC. MMWR Morb Mortal Wkly Rep. 2011 and 2012

Tardiness in rolling out PrEP

The 7 falsehoods of ARV prophylaxis to prevent HIV PrEP should only be used for prevention after all eligible AIDS patients are on treatment It is not safe to give ARVs to healthy people Asymptomatic people will not adhere to ARVs for prevention or treatment, especially when it is not provided by doctors Data on effectiveness of PrEP, especially in women, are inconsistent & doubtful efficacy Treatment in discordant couples ≠ community-level prevention Drug resistance from PrEP will undermine future AIDS treatment PrEP will increase HIV risk by ↓condom use We do not know how to provide PrEP and so need demonstration projects before PrEP roll-out

PrEP adherence varies by study & strongly correlates with effectiveness Pearson correlation = 0.86, p=0.003

ART by nurses is effective, sustainable and improved over time in rural SA

The 7 falsehoods of ARV prophylaxis to prevent HIV PrEP should only be used for prevention after all eligible AIDS patients are on treatment It is not safe to give ARVs to healthy people Asymptomatic people will not adhere to ARVs for prevention or treatment, especially when it is not provided by doctors Data on effectiveness of PrEP, especially in women, are inconsistent & doubtful efficacy Treatment in discordant couples ≠ community-level prevention Drug resistance from PrEP will undermine future AIDS treatment PrEP will increase HIV risk by ↓condom use We do not know how to provide PrEP and so need demonstration projects before PrEP roll-out

PrEP effectiveness is high in men & women with detectable tenofovir

The 7 falsehoods of ARV prophylaxis to prevent HIV PrEP should only be used for prevention after all eligible AIDS patients are on treatment It is not safe to give ARVs to healthy people Asymptomatic people will not adhere to ARVs for prevention or treatment, especially when it is not provided by doctors Data on effectiveness of PrEP, especially in women, are inconsistent & doubtful efficacy Trials in discordant couples ≠ community-level prevention Drug resistance from PrEP will undermine future AIDS treatment PrEP will increase HIV risk by ↓condom use We do not know how to provide PrEP and so need demonstration projects before PrEP roll-out

High ART coverage reduces HIV transmission & increases survival in a rural African community

The 7 falsehoods of ARV prophylaxis to prevent HIV PrEP should only be used for prevention after all eligible AIDS patients are on treatment It is not safe to give ARVs to healthy people Asymptomatic people will not adhere to ARVs for prevention or treatment, especially when it is not provided by doctors Data on effectiveness of PrEP, especially in women, are inconsistent & doubtful efficacy Trials in discordant couples ≠ community-level prevention Drug resistance from PrEP will undermine future AIDS treatment PrEP will increase HIV risk by ↓condom use We do not know how to provide PrEP and so need demonstration projects before PrEP roll-out

Drug resistance and condom use in PrEP / ART Estimated prevalence of drug resistance after 10 years (2012–2022) ART Overlapping ART + PrEP 10 8 6 4 2 Prevalence of drug resistance 6.6 4.2 2.4 0.5 0.3 8.2 4.6 3.3 0.2 0.1 PrEP PrEP transmitted resistance PrEP acquired resistance Overall ART acquired resistance ART transmitted resistance Source: Abbas U, 2013 Self-reported condom use in the CAPRISA 004 trial Source: Adapted from Abdool Karim Q. Science 2010

The 8 falsehoods of ARV prophylaxis to prevent HIV PrEP should only be used for prevention after all eligible AIDS patients are on treatment It is not safe to give ARVs to healthy people Asymptomatic healthy people will not adhere to ARVs for prevention or treatment Data on effectiveness of PrEP, especially in women, are inconsistent & doubtful efficacy Trials in discordant couples ≠ community-level prevention Drug resistance from PrEP will undermine future AIDS treatment PrEP will increase HIV risk by ↓condom use We do not know how to provide PrEP and so need demonstration projects before PrEP roll-out

Early experiences with implementing PrEP in San Francisco 49% (261/531) of eligible individuals offered PrEP in a STD clinic setting did initiate PrEP 59% (70/118) of those referred for PrEP in a Reproductive Health program did initiate PrEP 64% (7/11) of women with HIV+ve male partners initiated PrEP in prenatal or preconception care

Key Population 1: PrEP & TasP for young women in Africa Women acquire HIV ±8 years earlier than men <9 10-14 Prevalence (%) 15-19 20-24 25-29 30-39 40-49 2 4 6 8 10 Female Male >49 1990 Source: Abdool Karim Q, Abdool Karim SS, Singh B, Short R, Ngxongo S. Seroprevalence of HIV infection in rural South Africa. AIDS 1992, 6:1535-1539

High burden of HIV in young women in Africa: HIV in 15–24 year men and women (2008–2011) Young women have up to 8 times more HIV than men Zimbabwe Source: Adapted from UNAIDS 2012

Key Population 2: TasP & PrEP for MSM Country HIV prevalence among MSM (%, 95%CI) Population prevalence (>15 years) % HIV prevalence among MSM vs general population scenario 1: MSM predominant mode of exposure for HIV infection in the population Mexico 25.6 (24.8-26.5) 0.26 98.5 Bolivia 21.2 (17.6-24.7) 0.13 163.1 scenario 2: MSM risk occur within established HIV epidemics driven by IDU Serbia 8.7 (5.4-12.0) 0.08 108.8 Georgia 5.3 (1.2-9.4) 0.07 75.7 Scenario 3: MSM risks in context mature & widespread HIV epidemics among heterosexuals Nigeria 13.5 (12.0-15.0) 2.88 4.7 Sudan 8.8 (7.1-10.4) 1.26 7.0 Source: Beyrer et al. Epidemiol Rev 2010; 32: 137-51

Key population 3: PrEP & TasP for IDUs Country Country prevalence of IDU (%) HIV prevalence among IDUs (%) HIV prevalence among IDU vs general population Ecuador 0.59 28.8 106.6 Bolivia 221.3 Argentina 0.29 49.7 124.3 Poland 1.50 8.9 148.3 Serbia 27.0 338.0 Armenia 0.10 13.4 134.0 China 0.19 12.3 175.7 Indonesia 0.13 42.5 265.6 Source: Beyrer et al. Epidemiol Rev 2010; 32: 137-51

What are the potential gains from PrEP in Key Populations? NNT* Overall 62 Any cocaine use in the past month 12 Any anal sex with an HIV+ partner* 43 Receptive anal intercourse without a condom Only negative Unknown serostatus HIV positive 15 41 24 Number of partners 1 2-5 >5 100 60 58 Self-reported STI CAPRISA 004 *number needed to treat

Conclusion There is new hope in HIV prevention… More positive trials since July 2010 than in previous 29 years Treatment for prevention in particular provides huge hope Microbicides and oral PrEP: Promising new HIV prevention technologies for women, MSM and IDU Need to convert hope into actual benefit – Fast-track implementation for Key Populations