HIV Prevention Recent Advances and Implications for the Caribbean Chris Behrens, MD CCAS/CHART Conference Barbados, August 2010
Cases 200 180 160 140 120 100 80 60 40 20 0 Year HIV Cases AIDS Cases HIV Deaths Barbados HIV/AIDS Surveillance Report 2008 - Dr.D. Babb, MOH
Cumulative Cases 3500 3000 2500 2000 1500 1000 500 0 Year Cumulative HIV Cases Cumulative AIDS Cases Cumulative HIV Deaths Cumulative PLHIV Barbados HIV/AIDS Surveillance Report 2008 - Dr.D. Babb, MOH
Why the increase in emphasis on HIV Prevention? Globally, new infections continue to outpace ART coverage: 2-3 new infections for every person started on ART Global funding for ART programs starting to level off while need continues to grow HIV Vaccine nowhere in the foreseeable future
Combination Prevention Mix of interventions applied to a given population/region should be: Evidence-based Tailored to local circumstances Know your epidemic! identify your Most At-Risk Populations (MARPs) In your country, where will the next 100 HIV infections come from?
Recent Advances in HIV Prevention PMTCT Adult Male Circumcision (AMC) Antiretroviral Therapy Topical microbicides Positive Prevention
Recent Advances in Biomedical Interventions for HIV Prevention PMTCT Adult Male Circumcision (AMC) Antiretroviral Therapy Topical microbicides Positive Prevention
Mother to Child HIV Transmission in the U.S. Over Time Slide courtesy Lynne Mofenson, MD
Women & Infants Transmission Study (WITS) J Acquir Immune Defic Syndr 2002 April 15;29(5):484-494
Prevention, Prevention, Prevention Where are we in 2010? Antiretroviral Therapy for HIV Infection in Infants and Children: Towards Universal Access. 2010 Revision, WHO
From 29% in 07 to 52% in 08 - an 80% increase!
Year Infant Cases Maternal Factor 2004 2 untested, NVP 2005 0 2006 1 HAART, poor adh. bf 2007 0 2008 0
Barriers to uptake of PMTCT interventions 15
Recent Advances in Biomedical Interventions for HIV Prevention PMTCT Adult Male Circumcision (AMC) Antiretroviral Therapy Topical microbicides Positive Prevention
Epidemiologic association between circumcision & HIV Prevalence of HIV Infection, 2007 Prevalence of Male Circumcision, 2007
Randomized Clinical Trials Orange Farm Township, South Africa - France - 3,274 men aged 18-24 years Kisumu, Kenya - US and Canada - 2,784 men aged 18 24 years Rakai District, Uganda - US - 4,996 men aged 15 49 years Total: 11,054 men
Circumcision: Reduced HIV Infection Risk Trial Intent-to-Treat (95% CI) Orange Farm 60% (0.32,0.76) Kisumu 53% (0.22-0.78) Rakai 51% (0.16, 0.72) As-Treated (95% CI) 76% (0.54-0.86) 60% (O.32-0.77) 55% (O.22-O.75)
MC Service Delivery Update, Jan 2010 Country Botswana Kenya South Africa Swaziland Zambia Zimbabwe Begin date Apr 2009 Sept 2008 Jan 2008 Jan 2008 July 2009 May 2009 No. of MC's No. of MCs Nov Dec 09 4326 90 396 14 253 5122 16 801 3000 580 36 000 1547 1816 6171 1510 CROI 2010 17th Conference on Retroviruses and Opportunistic Infections
Global Recommendations Countries with high prevalence (>15%), generalized heterosexual HIV epidemics and low rates of MC should consider urgently scaling up access to MC services 13 countries identified: Botswana, Kenya, Lesotho, Malawi, Mozambique, Namibia, Rwanda, South Africa, Swaziland, Tanzania, Uganda, Zambia and Zimbabwe Consider ethics, communication, culture, health systems, funding, gender, comprehensive prevention strategies CROI 2010 17th Conference on Retroviruses and Opportunistic Infections
Recent Advances in Biomedical Interventions for HIV Prevention PMTCT Adult Male Circumcision (AMC) Antiretroviral Therapy Topical microbicides Positive Prevention
HIV transmission rate, per coital act, by plasma viral load of source partner - Rakai HIV transmission rate (per coital act) The Lancet Volume 357, Issue 9263, 14 April 2001, Pages 1149-1153
www.thelancet.com Published online May 27, 2010 DOI:10.1016/S0140-6736(10)60705-2
3,381 HIV-serodiscordant couples from Partners in Prevention HSV/HIV Transmission Study www.thelancet.com Published online May 27, 2010 DOI:10.1016/S0140-6736(10)60705-2
JAMA, June 10, 2009 Vol 301, No. 22 Bull World Health Organ 2009;87:488
Mathematical Model: Universal ART in SA Lancet, Volume 373, Issue 9657, Pages 48-57, 3 January 2009
Patients (n) Reduction in New HIV Diagnoses in BC: Testing, HAART, and Community VL Period of declining new HIV diagnoses in BC coincident with increased HIV testing rates, increased uptake of antiretroviral therapy, and decrease in community viral load (1996-2008) Decline in new HIV diagnoses despite increases in syphilis, gonorrhea, chlamydia 12,000 10,000 8000 6000 4000 2000 New HIV+ diagnoses (all) Censored at the time of death or move 1400 1200 1000 800 600 400 200 New HIV+ Diagnoses (n) HIV-1 RNA, copies/ml < 500 500-3499 3500-9999 10,000-49,999 50,000 0 0 Montaner J, et al. CROI 2010. Abstract 88LB.
Das M, et al. CROI 2010. Abstract 33.
Das M, et al. CROI 2010. Abstract 33.
Just to meet the minimal W.H.O. guidelines, donations would have to treble instead of going flat.
Recent Advances in Biomedical Interventions for HIV Prevention PMTCT Adult Male Circumcision (AMC) Antiretroviral Therapy Topical microbicides Positive Prevention
Topical Microbicides Urgent need for prevention method that women can control Multiple prior products promising in theory, disappointing in clinical trials CAPRISA 004: tenofovir gel
CAPRISA 004: 1% Tenofovir Microbicide Gel for Prevention of HIV in Women Randomized, placebo-controlled, double-blind, proof-of-concept study conducted at 2 sites in South Africa HIV-uninfected women, at high risk of HIV, 2 vaginal sex acts within 30 days of screening (N = 889)* 1% Tenofovir Gel (n = 445) Placebo Gel (n = 444) Study continued until 92 HIV infections observed *N = 889 enrolled and eligible subjects from screened population of 2160 subjects. Common causes of exclusion included HIV infection (n = 536), failure to return for further evaluation (n = 142), no sexual activity (n = 132), coenrollment in a separate study (n = 135), pregnancy (n = 51). Gel applied using BAT 24 regimen: 1 gel dose up to 12 hrs before sex; 1 gel dose as soon after sex as possible within 12 hrs after sex; maximum of 2 doses to be used within 24-hr period. Abdool Karim Q, et al. Science DOI: 10.1126/science.1193748. Abdool Karim Q, et al. AIDS 2010. Abstract TUSS0202.
Incidence Rate (Infections/100 PY) CAPRISA: Reduced HIV Incidence With Tenofovir vs Placebo Gel Tenofovir gel associated with decrease in HIV incidence [1] 50% decrease at 12 mos 39% decrease at 30 mos Tenofovir Placebo Tenofovir Efficacy vs Levels of Adherence Adherence Level, % n No. of Infections Efficacy, % > 80 336 36 54 50-80 181 20 38 < 50 367 41 28 12 10 8 6 4 2 0 P =.007 P =.017 5.2 10.5 5.6 9.1 cervicovaginal fluid tenofovir concentrations associated with HIV seroconversion [2] No HIV resistance to tenofovir in patients infected while using gel Use of tenofovir gel also associated with 51% decrease in HSV-2 infection [3] Mo 12 Mo 30 1. Abdool Karim Q, et al. Science DOI: 10.1126/science.1193748. 2. Kashuba A, et al. AIDS 2010. Abstract TUSS0203. 3. Abdool Karim S, et al. AIDS 2010. Abstract TUSS0204.
What Next After CAPRISA 004?
Recent Advances in Biomedical Interventions for HIV Prevention PMTCT Adult Male Circumcision (AMC) Antiretroviral Therapy Topical microbicides Positive Prevention
Positive Prevention Addressing HIV prevention with people aware of positive serostatus Addressing the need not to transmit HIV to others (spouses, family, children, partners) Integrating and prioritizing prevention as part of care of PLWH
Recommendations for Incorporating HIV Prevention into HIV Medical Care Developed by CDC, HRSA, NIH, HIVMA, with evidence-based approach Apply to medical care of all HIV-infected adolescents and adults Intended for those providing medical care to HIV-positive persons CDC/HRSA/NIH/IDSA Recommendations 39
What are the Recommendations? Medical providers can substantially affect HIV transmission when they screen for risk behaviors identify and treat other STDs communicate prevention messages discuss sexual and drug-use behavior positively reinforce changes to safer behavior refer patients for services (substance abuse treatment) facilitate partner notification, counseling, and testing CDC/HRSA/NIH/IDSA Recommendations
State of the Art Evidence-based Interventions Condom and lubricant promotion and distribution Review of 62 studies from sub-saharan Africa concluded that interventions promoting condoms can significantly increase levels of self-reported condom use in some populations. HIV testing and counseling Most HIV positive persons who know their status will reduce their risk behaviors to protect their sexual and injection partners.
EBI cont d Sexually transmitted infections screening and treatment STI control programs reduce STIs in commercial sex workers and their clients; evidence of STI control in reducing HIV among sex workers remains mixed. HIV care and treatment Drug using populations Substance abuse treatment, including medication assisted therapy Access to sterile syringes and safe disposal of injection equipment Other populations Male circumcision
EBI cont d Peer education and outreach When accompanied by risk reduction counseling and supplies provision (condom, bleach kits) is effective in reducing sexual and/or drug-using risk behaviors Significantly associated with increased levels of HIV knowledge, reduced STI prevalence, increased condom use, and reduced IDU equipment sharing. Risk reduction counseling Can have a positive impact on IDU sexual risk behaviors Decreases STI or HIV among sex workers
HIV Prevention in the Caribbean Implications for implementation
HIV Prevention in the Caribbean Know your epidemic Where will the next 100 infections come from? Expand coverage of interventions that work: Ensure broad availability of PMTCT services Streamline the PMTCT Cascade, aggressively track mothers who fall through the cracks Lobby for expansion of ART coverage?
HIV Prevention in the Caribbean Increase the proportion of individuals who know their status AND enroll in care Opt-out testing, PITC Strengthen referral links, f/u on those who fail to follow through on referrals Public Messaging Decrease Stigma & Discrimination especially among health care workers!
HIV Prevention in the Caribbean Train clinicians in proven Positive Prevention interventions but appropriately tailored to local context Continue to promote condoms, ABC Anticipate arrival of tenofovir gel but when? Other approaches?
Extra slides
Some examples Domestic International
For example EPPEC Outcomes Provider-led interventions led to significantly greater reduction in sexual risk at 12 months compared to the assessment only group. Brief risk assessment and provider-led interventions appear to have the greatest effect on reduction in sexual risk among patients seen in clinical settings.
Impact of MC Scale-up PLoS Medicine 2009 doi:10.1371/journal.pmed.1000109.g001 CROI 2010 17th Conference on Retroviruses and Opportunistic Infections
Almost Three years later What Progress has been made??? March 2007 Montreux Meeting WHO/UNAIDS 2008 2009 Recommendations 2010 CROI 2010 17th Conference on Retroviruses and Opportunistic Infections
Risk of HIV Transmission by VL & ART Use AIDS 2009, 23:1397 1404
Where can clinicians have an impact?
WHO Progress Report 2009
Cost and Impact of MC Scaling up of MC to reach 80% of adult and newborn males in 14 African countries by 2015: Could prevent more than 4 million adult HIV infections over 15 years (2009 2025) Could result in cost savings of US$20.2 billion between 2009 2025 with an overall investment of approx *US$ 4 billion Would require almost 12 million MCs to be performed in the peak year, 2012 Source (* adapted): USAID/HPI (2009) The Potential Cost and Impact of Expanding Male Circumcision in Eastern and Southern Africa http://www.malecircumcision.org/research/policy_briefs.htm CROI 2010 17th Conference on Retroviruses and Opportunistic Infections
Botswana MC Program Costs and Cost Savings (Estimates) US$ (Million) US$ (Million) 25 20 350 300 250 Cum cost Cum Saving 15 Annual cost 200 10 Annual saving 150 100 5 50 0 0 2009 2011 2013 2015 2017 2019 2021 2023 2025 2009 2011 2013 2015 2017 2019 2021 2023 2025 Adapted from: USAID/HPI (2009) The Potential Cost and Impact of Expanding Male Circumcision in Botswana http://www.malecircumcision.org/research/policy_briefs.htm CROI 2010 17th Conference on Retroviruses and Opportunistic Infections
Progress made on Male Circumcision to end 2009 Male circumcision prevalence at country level, 2006 Kenya Policy, strategy, Training, QA, expanded service delivery, M&E Rwanda Situation analysis, pilot service delivery in military South Africa, Zimbabwe Situation analysis, draft policy, pilot sites Namibia Draft policy, draft communications strategy, draft M&E Lesotho Situation analysis, policy development underway, draft strategy Uganda Situation analysis, policy development Tanzania, Mozambique, Malawi Situation analysis, pilot sites Zambia Policy note, Strategy, national and regional trainings Botswana Situation analysis, strategy, communications, training, expanded service delivery, M&E Swaziland Policy, strategy and implementation plan, QA CROI 2010 17th Conference on Retroviruses and Opportunistic Infections
Oral Pre- and Post-exposure prophylaxis Oral TDF +/- FTC given to high-risk populations (e.g CSWs), either daily or intermittently