Implementation science realizing the hiv prevention revolution
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Implementation Science: Realizing the HIV Prevention Revolution. Nelly R. Mugo, MD, MBChB , MMed , Kenyatta National Hospital/ University of Nairobi. University of Washington. T he HIV pandemic remains a global health challenge. From 1980s to present Approximately 30 million deaths

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Implementation Science: Realizing the HIV Prevention Revolution

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Implementation Science: Realizing the HIV Prevention Revolution

Nelly R. Mugo, MD, MBChB, MMed,

Kenyatta National Hospital/ University of Nairobi.

University of Washington

The HIV pandemic remains a global health challenge

  • From 1980s to present

    • Approximately 30 million deaths

  • 2010 HIV global estimates

    • 34 million people living with HIV/AIDS

    • 2.7 million newly infected

    • 1.8 million deaths

  • AIDS is still the commonest cause of death in Africa and 6th most common globally

The HIV prevention revolution

  • 30 years into the HIV epidemic, new research has demonstrated that we now have powerful interventions to prevent new infections

  • For the first time, we can begin to visualize a future free from HIV/AIDS as a feasible goal

Changing how we deliver HIV prevention services: road map

  • Think populations for targeted interventions

  • Prioritize interventions that work within populations

  • Deliver in combination and with high coverage for high impact

Roadmap for the prevention revolution

  • Think populations for targeted interventions

  • Prioritize interventions that work

  • Deliver in combination and with high coverage

Source of new HIV infections in generalized epidemic: the epidemic within epidemics

Swaziland, Lesotho, Uganda, Malawi heterosexual unions contribute the majority of new infections

Heterosexual couples

  • The majority of new HIV-1 cases in sub-Saharan Africa occur among couples

    • HIV-serodiscordancy is common: 50% of partners of HIV-1 infected persons are HIV uninfected

    • Risk of HIV transmission in couples who do not know they are sero-discordant ~14%

  • Without couples counseling and testing , it may be unclear who is at risk and a target for intervention

    • Among sero-discordant couples desire for children overshadows fear of infection and is a risk driver

Marginalized populationsrequire prioritized HIV interventions

  • HIV prevalence is high (Data from *SWOP-Kenya)

    • 40% among MSM

    • 28% among female sex workers

    • And a minority correctly use condoms

  • Social and policy environment keep these at risk populations marginalized and reluctant to seek health services

    • Sodomy in Kenya is illegal with a 14 year jail sentence

    • Experience social condemnation, physical and sexual abuse

  • *Sex workers project (SWOP), University of Nairobi

    There can be no HIV revolution without youth

    Globally, 42% of new HIV infections are among youth age 15-24 years

    • 80% (4 million) of these infections are in sub-Saharan Africa

    • Young women, have twice the HIV infection rates as young men

    High risk in young women: Kenya

    Kenya AIDS Indicator Survey 2007

    • 65% of new infections among women occur before age 35 years

    • The same pattern holds true of South and East African countries

    Thinking population

    • Prioritize activities

      • Specific to priority population

      • Address vulnerabilities

      • Deliver comprehensive packages designed for populations

    *Jewkes Lancet 2010

    Roadmap for the prevention revolution

    • Think populations for targeted interventions

    • Prioritize interventions that work

    • Deliver in combination and with high coverage

    ARVs for prevention: breakthroughs

    • 2011: Research provided clear and unequivocal evidence that antiretroviral treatment and PrEP work for the prevention of sexual transmission of HIV

    • 2012: We know the what. The question now is HOW?

    HPTN 052: randomized clinical trial of immediate vs delayed ART in couples

    Total HIV-1 Transmission Events: 39

    Unlinked or TBD Transmissions: 11

    Linked Transmissions: 28

    One infection in immediate arm was soon after HAART

    • 96% reduction in HIV transmission

    Immediate ART: 1

    Delayed ART: 27

    p < 0.001

    Cohen et al NEJM 2011.

    ART only works when taken

    In HPTN 052, viral suppression was near-universal, reflecting intensive strategies, including quarterly monitoring and individual counseling, to achieve near-perfect adherence

    Immediate Arm

    Delayed Arm (not on ART)

    Delayed Arm (on ART)

    Cohen et al NEJM 2011.

    Pivotal randomized, placebo-controlled trials of PrEP for HIV prevention

    Grant et al N Engl J Med 2010

    Thigpen et al N Engl J Med 2012

    Baeten et al N Engl J Med 2012

    PrEP (like ART) works when taken

    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

    Risk perception: Behaviourmatters

    What motivates PrEP use?

    • Serodiscordant couples have a known HIV+ partner, decided to stay together, motivates high adherence

    • FEM-PrEP, young women

      • 70% perceived themselves to be at little or no HIV risk resulting in lower adherence

      • Yet HIV incidence was 5% per year!

        Risk perception is key for any strategy to be effective

    PrEPis not lifelong, it is for a season

    • Adolescent women present a season of vulnerability

      • High HIV incidence East and Southern Africa ages 16-24 years

    • HIV serodiscordant couples trying to conceive

    • Young men who have sex with men

    • Couples where there is intimate partner violence, new partner, depression, alcohol & drug use and perhaps in conflict zones

    • USA FDA reviewed and approved a label indication for emtricitabine/tenofovir(Truvada®) for HIV prevention on July 16th 2012

    • We now have a powerful tool, that can safely be used by populations of vulnerable HIV-negative individuals

    • We have been waiting decades for a tool under the control of a negative woman or man.

    It was said that ART could not be done

    “…. In Africa, a higher proportionof patients are likely to fall into the category of potentialpoor adherers unless resource intensive adherence programmesare available.”

    Remember the critiques of ART roll-out in Africa: it was done and we can do more

    Antiretroviral therapy in Africa Stevens et al. BMJ  2004

    Treatment of STIs

    Male circumcision


    for women

    Grosskurth H, Lancet 2000

    Auvert B, PloS Med 2005

    Gray R, Lancet 2007

    Bailey R, Lancet 2007

    Abdool Karim Q, Science 2010

    Male & female condoms

    Structural / legal


    PREVENTION combined interventions

    HIV Counselling and Testing

    Oral pre-exposure prophylaxis

    Coates T, Lancet 2000

    Grant R, NEJM 2010 (MSM)

    Baeten J , NEJM 2012 (couples)

    Thigpen, NEJM, 2012 (Heterosexuals)

    Behavioural Intervention

    Post Exposure

    prophylaxis (PEP)

    Treatment for prevention

    Donnell D, Lancet 2010

    Cohen M, NEJM 2011

    Scheckter M, 2002

    Long-lasting protection from VMMC‘a cut with extended benefit’


    % HIV Incidence

    Similar results from Kenya and South Africa trial sites, no evidence of risk compensation

    68% Effectiveness –

    Extending long after RCT



    (Last trial visit)






    Results from extended Rakai study (from Kong et al, CROI, 2011)

    Prioritize what works

    • FINALLY, we have additional tools for a package of interventions that work – we have never been here before

    • It is time to revisit and revise how interventions are prioritized – time to focus resources and efforts on proven and impactful interventions

      • We have to be ready to get rid of policies and approaches that do not work

    • The revolution is targeting populations and providing relevant packages

    Roadmap for the prevention revolution

    • Think populations for targeted interventions

    • Prioritize interventions that work

    • Deliver in combination and with high coverage

    Combination high impact HIV prevention

    • Synergies of effective interventions in combination:

    • Reduce HIV infectiousness (eg ART, condoms), and

    • Reduce HIV susceptibility (eg male circumcision, PrEP, vaccine) & behavioral interventions with

  • High coverage

  • Coates, Lancet 2008

    Synergies– HIV prevention is a team effort: Cambodia 1.0




    STI case management


    Local Authority


    Health Workers




    brothel owners

    Sex workers

    STD Clinic

    Media (TV, radio, News paper)

    Special campaigns (Posters, leaflets, bill boards…)

    For high coverage, Cambodia has a framework that includes both social and medical care services to reach MSMs

    Mean ChhiVun, AIDS 2012

    Testing is the gateway to HIV prevention and care

    • Acceptability of HIV testing is high in large scale campaigns and Home based community testing

    • Testing must be linked to services & not simply numbers

    • Requires systems for effective linkage to services

    In Kenya: 41,040 people tested in 1 week during a community outreach

    Navneet Garg | Global Business Manager | Vestergaard Frandsen

    Delivery of highly effective prevention interventions will not be without challenges

    The leaky cascade

    • We need

    • high testing coverage

    • linkage to care

    • viral suppression

    • to reduce infectiousness and HIV incidence at population levels

    Willingness to start antiretrovirals

    • Soweto, South Africa:7287 adults tested for HIV

      2562 (35%) HIV infected

      743 (29%) eligible for ART (CD4<200***)

      148 (20%) refused

      • Most common reason for refusal was feeling well

    Katz et al. AIDS 2011

    We have little experience with starting ART in asymptomatic persons…

    • Among HIV+ members of discordant couples in Thika, Kenya

    • 42% of men and 31% of HIV infected women said they would NOT be willing to initiate ART solely to lower the chance of infecting their partner

    • Concerns: Fear of side effects of ART, stigma , pill burden and potential for developing resistance

    Heffron et al JAIDS 2012 CROI 2012

    Improving testing & linkage to care

    • Patient empowerment improves retention in care

    Improving testing & linkage to care

    • Strategies that have worked

      • Home based HIV testing

      • Point of Care CD4 count

      • Community delivery of ART


    *Barnabas TasP 2012

    Parallel challenges, parallel opportunities

    Demonstration project approach – ART with PrEP as a bridge in couples

    ART and PrEP work together to drive down HIV risk

    Roll-out of male circumcision: substantial country differences

    % of target achieved

    Lessons learnt from VMMC implementation Kenya

    • The HIV prevention plan must be community owned- at all levels from government to local communities

      • In Kenya the Luo council of elders endorsed MMC

      • Educate the public through social media

    • For population impact: target & coverage matters

    • Be flexible & creative

    • Monitor and Evaluate to catch problems early and intervene

      JUST DO IT

    Adapted from KawangoAgot

    ARVs have made elimination of mother to child HIV transmission a feasible goal

    This has required combination of biomedical and behavioural interventions

    Source: Mahy, Stover, Kiragu et al, Sex Transm Infect 2010 86: ii48-ii55, 2011


    • Target Population

      • We need to change course and target population, then apply interventions that fit the populations

      • Youth are key, and should be prioritized if we are to reverse the tide of this epidemic

      • Programs should reflect this mind shift and start with populations then provide appropriate intervention package

    • Proven Intervention

      • we finally have tools that are proven to be highly efficacious,

      • we must carefully select both biomedical and behavioral tools appropriate to each at risk population

    • Coverage

      • For high impact, must have high coverage, link testing to services

      • Reduce leakages in prevention cascade

      • Process of prevention needs to belong to communities

    Give them a future without HIV

    • We have a real opportunity in the history of this disease to make a remarkable difference and save lives –this is not a choice but obligation

    • We shall be judged on how well we utilized the knowledge we have accrued to save men and women from getting infected with HIV

    • Hopefully fulfilling a dream for future generations of an HIV free life


    IAS Conference organizers

    Kenyatta National Hospital

    All investigators, advocates, sponsors and seekers of new HIV prevention tools

    Kenya Prevention Revolution team

    NdukuKilonzo: Kenya LVCT, Peter Cherutich: Kenya NASCOP

    Jared Baeten, Connie Celum: University of Washington

    All of you for listening


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