Is this the end of AIDS? New advances in HIV prevention. James McIntyre Anova Health Institute and University of Cape Town School of Public Health

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1 Is this the end of AIDS? New advances in HIV prevention. James McIntyre Anova Health Institute and University of Cape Town School of Public Health

2 Thirty years of AIDS July 3, 1981

3 A generation in the shadow of AIDS...

4 Global Estimates of People Living with HIV/AIDS,

5 Thirty years into the epidemic Number of people living with HIV 4.0 Number of people newly infected with HIV 40 People newly infected with HIV and deaths due to AIDS (Millions) Number of deaths due to AIDS People living with HIV/AIDS (Millions) UNAIDS/WHO Epi update, 2009

6 Global estimates for adults and children 2009 People living with HIV New HIV infections in 2009 Deaths due to AIDS in million [ million] 2.6 million [ million] 1.8 million [ million] Each day people die of AIDS Each day more people on Antiretroviral Therapy

7 Over 7000 new HIV infections a day in 2009 About 97% are in low and middle income countries About 1000 are in children under 15 years of age About 6000 are in adults aged 15 years and older, of whom: almost 51% are among women about 41% are among young people (15-24)

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9 Thirty years of AIDS First South African publication: 1983: two cases in homosexual men, both died in 1982

10 Thirty years of AIDS September 1986: The present status of AIDS cases in the RSA is: (i) South African residents 30 cases comprised of homosexual/bisexual men (26), heterosexual (I), blood transfusion AIDS (I) and haemophiliacs (2); all these are white males; R Sher, SAMJ, 1986

11 Thirty years of AIDS.. has a new microbe arisen like a phoenix from the cauldron of evolution and flourished here and now because of the special social and sexual circumstances of the times? Ruben Sher, SAMJ 1986

12 A decade of denial

13 HIV trends in sub-saharan Africa

14 Young women at highest risk in Africa

15 HIV prevalence, by sex and age, South Africa, 2008 Shisana O, Rehle T, Simbayi LC, Zuma K, Jooste S, Pillay-van-Wyk V, Mbelle N, Van Zyl J, Parker W, Zungu NP, Pezi S & the SABSSM III Implementation Team (2009) South African national HIV prevalence, incidence, behaviour and communication survey 2008: A turning tide among teenagers? Cape Town: HSRC Press

16 Reality Check: a question of scale Norway : total population 4.9 millio n South Africa: people living with HIV 5.3 millio n

17 Back on track... South Africa has rapidly scaled up its prevention of mother to child HIV transmission (PMTCT) programmes. By 2010, PMTCT was offered at 98% of health facilities with virtual universal coverage of mothers booking and delivering in health facilities. In 2010, early transmission from mother to child was found to be 3.5 percent in South Africa, and only 1.1 percent of 4- to 8-week-old infants in the country were infected with HIV. Rollout of antiretroviral therapy continues to be successful, with 1.4 million persons started on antiretroviral therapy as at the end of June Treatment initiation rates have reached 30,000 per month. Revision of the treatment guidelines in 2009 and 2011 has increased the threshold for ART treatment to CD4 count 350, and to initiate all HIV positive infants regardless of CD4 level

18 Game Changer interventions proposed in the Draft NSP : Scaling up and improving the quality of key prevention and treatment programmes, including male and female condom distribution (including for key populations), MMC, prevention of mother to child transmission, and ART; Combination prevention interventions that are targeted depending on epidemiology; Introducing new prevention interventions rapidly as informed by evidence, e.g. microbicides, and pre-exposure prophylaxis for key populations; and Protecting children and reducing their HIV and TB vulnerability, including keeping girls in school for as long as possible.

19 Antiretroviral treatment: saving lives

20 Annual AIDS-related deaths by region:

21 Antiretroviral treatment is saving lives At the end of 2009, people were receiving antiretroviral therapy in lowand middle income countries This is an increase of over 1.2 million people from December This represents a 30% rise from a year earlier and a 13- fold increase in six years.

22 Number of people receiving antiretroviral therapy in low- and middleincome countries, by region,

23 A long way to go to achieve universal access to treatment Among 144 low- and middle-income countries, eight had already achieved universal access to antiretroviral therapy at the end of 2009, providing treatment to at least 80% of patients in need. WHO

24 Is universal access possible? Successful provision of universal treatment access may be critically dependent on reducing the number of new infections 6.6 million are now on antiretroviral treatment (ART) 9 million are waiting to receive it For every person starting ART two people are newly infected 20 million more people predicted to acquire HIV by 2031: Increasing potential treatment costs up to $35 billion a year. Shattock IAS 2011

25 A renaissance of hope This is an exciting time for science. These studies offer unprecedented opportunities to expand the toolkit for prevention. Gottfried Hirnschall, Director, HIV/AIDS, World Health Organization As we get more scientific data, the ability to contain the epidemic by multiple weapons gets better and better. Anthony Fauci, Director, National Institute of Allergy and Infectious Diseases This can be a momentum changer. This could be an epidemic where we see a major turnaround in a single generation. Paul DeLay, Deputy Executive Director, UNAIDS

26 The State of HIV Prevention Strategies: 2010

27 The State of HIV Prevention Strategies: 2011? Condoms Male Circumcision ARV Prophylaxis: PMTCT Sterile needle exchange for intravenous drug users ARV Prophylaxis: PEP, PrEP Antiretroviral based Microbicides Vaccines Counselling & Testing HSV-2 Suppressive therapy Cervical Barriers STI Treatment HIV PREVENTION STRATEGIES

28 Opportunities for biomedical interventions YEARS HOURS 72 HOURS YEARS Prior to exposure Exposure (pre-coital/coital) Exposure (pre-coital/coital) After infection Male circumcision Oral pre exposure prophylaxis (daily PrEP) Topical PrEP (daily gels or intra-vaginal rings (microbicides) Preventive Vaccines Oral pre exposure prophylaxis (intermittent PrEP) Coitally dependent topical PrEP (microbicides) Oral post exposure prophylaxis (PEP) Anti-retroviral therapy Immediate treatment of positive partners in discordant couples Treatment for prevention in all who test positive for HIV (T4P) Behavioural & structural components AVAC, Shattock IAS 2011

29 New biomedical intervention strategies Study Prime boost HIV Vaccine (Thai RV144) 1% tenofovir gel (Caprisa 004, Karim et al.) TDF/FTC oral PrEP in MSM (iprex, Grant et al 2010) Medical male circumcision (MMC) (Orange Farm, Rakai, Kisumu) TDF/FTC oral PrEP in heterosexuals (TDF2, CDC) TDF oral PrEP in serodiscordant Partner (Partners PrEP) TDF/FTC oral PrEP in serodiscordant Partner (Partners PrEP) Immediate ART for positive Partners (HPTN052) 0% % 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)* *Provisional Efficacy

30 Multi component prevention The failure of silver bullet single biomedical interventions has opened the way for a wider acceptance of the need for a multi component prevention approach HIV prevention requires a comprehensive approach, applying a combination of strategies that respond to the real needs of real people Only does not work for HIV prevention Coates et al, Lancet 2008

31 From ABC to A-Z Need to acknowledge the false divide between biomedical and behavioural strategies Implementation of successful biomedical interventions also provide opportunities to refocus on behaviour modifications, including: Strategies to reduce HIV risk linked to alcohol use Delaying sexual debut Decreasing HIV risk from drug abuse, including needle exchange programmes Reducing the risk from multiple concurrent partnerships

32 Medical Male Circumcision

33 Male Circumcision: bridging from research to reality Medical male circumcision reduced the risk of HIV infection in men in three randomised controlled trials by close to 60% Estimated that one HIV infection could be prevented for every five to 15 men circumcised in settings with high levels of HIV and low rates of male circumcision, at a cost of US $150 to $900 per HIV infection averted over 10 years Since 2007, WHO and UNAIDS have recommended male circumcision as an important HIV prevention strategy in countries with high rates of heterosexual HIV transmission and low rates of male circumcision.

34 Annual male circumcisions for HIV prevention in eight countries* in Eastern and Southern Africa, Thousands * Kenya, Malawi, Namibia, Rwanda, South Africa, Swaziland, Zambia and Zimbabwe Hankins IAS 2011

35 Achievement toward target of 80% coverage Hankins, 2011: Courtesy Emmanuel Njeuhmeli, PEPFAR

36 Male Circumcision: bridging from research to reality In 2010, South Africa instituted an aggressive rollout of a national medical male circumcision (MMC) programme. The goal is to reach 80% of men aged (approximately 4.3 million men) by As of June 2011, medical male circumcisions had been conducted.

37 Lessons from medical male circumcision for other new prevention technologies Need to address concerns about: Partial protection, risk compensation, behavioural inhibition Promotion of combination protection Gender equity Stigma and discrimination Mobilising demand and ensuring supply Competition for financial, human and service resources Hankins 2009

38 A vaccine for AIDS?

39 RV144 Acquisition Endpoint: Modified Intent to Treat (mitt) Probability of HIV-1 Infection (%) YEARS Placebo Vaccine Placebo Vaccine Vaccine infections: 51 Placebo infections: 74 p = 0.04 Efficacy: 31.2% 95% CI (OBF): 1.1, 51.2 month Events Efficacy 54% 60% 44% 36% 36%

40 Preventing mother- to-child transmission of HIV

41 PMTCT impact: infections averted among infants Infant infections averted Estimate of the annual number of infant infections averted through the provision of antiretroviral prophylaxis to HIV-positive pregnant women, globally, , UNAIDS 2009

42 Working towards an AIDS free generation by 2015

43 Elimination of MTCT by 2015? From talking to action... We can prevent mothers dying and babies becoming infected with HIV. That is why I am calling for the virtual elimination of mother-to-child transmission of HIV by 2015 Michel Sidibe, UNAIDS December 2009

44 Preventing mother-to-child transmission of HIV: Lessons of success and failure PMTCT led the way with combination prevention approaches: in promoting a four-pronged combination prevention approach in using treatment for prevention.

45 Antiretroviral prophylaxis: Pre-exposure Prophylaxis (PrEP) Antiretroviral microbicides

46 Pre-Exposure Prophylaxis Study Effect CAPRISA (TDF Gel) 39 50% iprex (Daily TDF) 44% FEM PrEP (Daily TDF) Stopped Partners (TFV/TDF) >70% Botswana (TDF) >60% Others in Progress Cohen IAS 2011

47 CAPRISA 004: HIV infection rates in the tenofovir and placebo gel groups: Kaplan-Meier survival probability 0.20 Probability of HIV infection Months of follow-up Cumulative HIV endpoints Years Cumulative women-years HIV incidence rates (Tenofovir vs Placebo) Effectiveness (p-value) 6.0 vs vs vs vs vs % (0.069) 50% (0.007) 47% (0.004) 40% (0.013) Placebo Tenofovir 39% (0.019) (0.017) p=0.019 p=0.017

48 PrEP for HIV prevention in men who have sex with men

49 Antiretroviral treatment: Treatment IS Prevention

50 HIV Treatment as Prevention? Compelling biological plausibility: ART reduces HIV in genital secretions Five observational reports What is the magnitude and durability of ART for prevention? Does early ART (for prevention) benefit an HIV infected person? POSITIVE RESULTS: Bunnell (JAIDS, 2007) Sullivan (IAS 2008) Donnell (Lancet, 2010) Romero (BMJ, 2010) NEGATIVE RESULTS: Wang (IAS, JAIDS, 2010) Cohen IAS 2011

51 HPTN discordant heterosexual couples 9 countries, 13 sites Randomization Immediate ART cells/uL AZT+3TC+EFV Deferred ART CD4 <250 Endpoints: i) HIV Transmission to partners ii) OIs and clinical Events iii) ART toxicity Cohen IAS 2011

52 HPTN 052 Modified by DSMB April 28, 2011 (DSMB meeting #11) Recommendation: Make the results available to the public (and study subjects) as soon as possible HPTN 052 is ongoing with all HIV infected subjects offered ART, regardless of CD4 count

53 HPTN 052 Prevention Results p<0.001 Cohen IAS 2011

54 HPTN 052: results Early ART prevented linked transmission of HIV Unlinked transmissions were noted despite intensive couples counseling Early ART reduced the number of clinical events observed

55 HPTN 052: Implications The HIV prevention effect demonstrated in HPTN 052 is the proof of a concept These results could inform The Test and Treat strategies Management of HIV discordant couples Cohen IAS 2011

56 Partners PrEP Study 4758 HIV serodiscordant couples (HIV+ partner not yet medically eligible for ART) Randomize HIV partners (normal liver, renal, hematologic function) TDF once daily FTC/TDF once daily Placebo once daily All receiving comprehensive HIV prevention services Follow couples for up to 36 months 1 endpoint: HIV infection in HIV partner Co 1 endpoint: Safety

57 Partners PrEP: Summary TDF and FTC/TDF PrEP definitively reduced risk of HIV acquisition, by 62% & 73%, respectively, in African men and women Similar efficacy between TDF & FTC/TDF HIV protection effect was robust in both women and men Study announcing findings 1.5 years earlier than expected TDF and FTC/TDF PrEP were safe & well tolerated Mild gastrointestinal side effects, predominantly in Month 1 No evidence of risk compensation Baeten IAS 2011

58 So what do these results mean? Guidelines for treatment and prevention likely to change Early treatment of infected adults appears to have major prevention benefits for uninfected partners: should be considered in discordant couples now Pre exposure prophylaxis is effective in reducing risk: adherence is key to successful use. Consideration of targeted use of PrEP in individuals and populations at high risk Implementation strategies need to be developed and funded

59 AIDS: is the end in sight?

60 Aids: is the end in sight? New prevention technologies antiretroviral preexposure prophylaxis, antiretroviral microbicides, male circumcision - provide hope for accelerated reduction in incidence The prevention benefits of antiretroviral treatment are being increasingly recognised Some success in preventive vaccine research Behaviour change remains difficult, but there are some indications of success in young people

61 Roadmap to reversing the epidemic Circumcision Treatment 4 prevention A combined research strategy for biomedical interventions is likely to provide the fastest, most tangible impact on HIV transmission ARV PrEP (oral, microbicide) Shattock et al Science. 2011;333:42-3 Partially effective vaccine Highly effective vaccine HIV incidence Behavioral and structural interventions

62 The Implementation gap We have many ways to prevent HIV infection. The sobering news is that only 20 percent of people who can benefit actually have access to prevention services. We have the scientific capability but there is an imbalance and a gap on the basis of science and on what we can deliver on the basis of public health. Tony Fauci, May 2010

63 Safety is paramount

64 Don t underestimate the stigma of taking ARV Adherence to PMTCT interventions, even as short-term and simple dosing regimens, has been affected by the stigma of treatment, and the fear of side effects Community education and preparation is crucial to success

65 Good regimens are not enough: health systems matter Somewhere over the counter? Good regimens need to reach the people Relying on broken health systems won t work Need for innovative alternatives now: Community distribution New technology (cell phones, internet)

66 Health Systems are in Crisis Wafaa El Sadr, 2009

67 Political will remains essential

68 The crisis of continued funding in the face of a global recession

69 Linking provision of new prevention technologies Prevention of new infections in women Prevention of transmission to sexual partners Prevention of transmission to infants New HIV prevention technologies Family planning & reproductive health services PMTCT services Pre-ART care Antiretroviral therapy Male health care Circumcision

70 The Coalition for Implementation Users Regulatory authorities Researchers Normative Agencies Successful implementation Manufacturers Policymakers Health care providers Media

71 Making the impossible, possible The difficult is what takes a little time; the impossible is what takes a little longer Fridtjof Nansen, ( ) Norwegian explorer, scientist, diplomat, humanitarian and 1922 Nobel Peace Prize Winner

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