Combination Prevention of HIV: What is it and where are we now? Farley R, Cleghorn MD, MPH – Futures Group Chief Knowledge Officer & Global Health Practice Leader USAID Mini-University 03.02.2015

WHAT IS COMBINATION HIV PREVENTION? “Combination HIV Prevention is the strategic, simultaneous use of different classes of prevention activities and interventions (biomedical, behavioral, social/structural) that operate on multiple levels (individual, relationship/network, community and societal) to respond to the specific needs of particular key groups and modes of transmission (key or vulnerable populations) and to make efficient use of resources through prioritization, partnership and engagement of affected communities.” UNAIDS 2010

The social ecological model of health promotion Mitigate both Proximal and Contributing risk Factors for HIV Transmission.

Most HIV prevention and treatment strategies have focused on the individual level, assuming individuals will defy or overcome social, economic and political constraints. Individuals Social and sexual networks Community, Organizations Society Inter-governmental, Global Need to mitigate both Proximal and Contributing risk Factors for HIV Transmission. Individuals

IMPLEMENTATION (PROGRAM) SCIENCE IN HEALTH “PILOTITIS” Population level outcomes Program level efforts Models & Pilot Studies Research Concepts Implementation Science Gap Impact Resources What intervention mix do country programs invest in for impact?

HEALTH: PROGRAM SUCCESS Doing enough (the right dose) of the right thing at the right time for the right people Coverage, quality and intensity of proven interventions Missing science on how these combine across sectors in programs, e.g. health & education Health markets include all sectors – public, middle and private

ARV prophylaxis SEXUAL HIV PREVENTION Medical Male circumcision Auvert B, PloS Med 2005 Gray R, Lancet 2007 Bailey R, Lancet 2007 Treatment of STIs Grosskurth H, Lancet 2000 Microbicides for women & some gay men Abdool Karim Q, Science 2010 Female Condoms Male Condoms SEXUAL HIV PREVENTION Grant R, NEJM 2010 (MSM) Baeten J , 2011 (Couples) Thigpen M, 2011 (Heterosexuals) Choopanya K, 2013 (IDU) Oral Pre-exposure prophylaxis (PrEP) HIV Counselling and Testing Coates T, Lancet 2000 Sweat M, Lancet 2011 Post Exposure prophylaxis (PEP) Scheckter M, 2002 Behavioural Change Treatment as 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

The core transmission dynamics distinction Epidemics CONCENTRATED if effective SW (sex worker), MSM (men-having-sex-with-men) and IDU (injection drug user) programs would prevent wider epidemic Epidemics GENERALIZED if epidemics would persist despite effective SW, MSM and IDU programs Epidemics MIXED if transmission sustained BOTH by SW, MSM and IDU and wider population

Concentrated, generalized and mixed epidemics Mixed/uncertain

Defining Combination Prevention: Ongoing trials in sub-Saharan Africa NIH’s Methods for Prevention Packages Program – MP3 I NIH’s Methods for Prevention Packages Program – MP3 II PEPFAR-funded effectiveness trials Gender-Specific Combination HIV Prevention for Youth in High-Burden Settings Gender-specific HIV packages for male and female youth delivered using community-based mobile health teams Kenya Methods for Prevention Packages Program Home-based HIV testing and targeted referrals for VMMC, ART, STI treatment, couples counseling and oral PrEP plus topical PrEP (if effective) South Africa and Uganda Johns Hopkins University with USAID funding Evaluation of the impact on HIV incidence of expanding population coverage of an integrated set of HIV prevention interventions DISCONTINUED Tanzania An HIV Prevention Package for Mochudi Behavioral interventions: VCT, partner notification, concurrency reduction, VMMC, condoms and ART for those with high viral load Botswana Acute Infection in Heterosexuals Standard vs. enhanced counseling vs. behavioral intervention plus 12-week ART to reduce viral load Malawi Comprehensive HIV Prevention Package for MSM in Southern Africa Package of behavioral, biomedical and community-level interventions Zambia and South Africa PopART/HPTN 071 A strategy linking household-based HIV testing to universal community-based HIV treatment South Africa and Zambia Enhance Prevention in Couples Behavioral counseling, ART for prevention (CD4<500) plus couples counseling, VMMC Lesotho Harvard School of Public Health with US CDC funding Evaluation of the impact on HIV incidence of expanding population coverage of an integrated set of HIV prevention interventions Botswana CHAMPS: Choices for Adolescent Methods of Prevention in South Africa Potentially PrEP, microbicides, HCT and circumcision—plus messaging and social marketing around these approaches South Africa In addition to the trials pictured, there are also evaluations ongoing in Europe, North and South America. For a complete list, visit avac.org/pxrd. AVAC Report 2012: Achieving the End – One year and counting. www,avac.org/report2012

PopART: Model structure for infected individuals. Cori A, Ayles H, Beyers N, Schaap A, Floyd S, et al. (2014) HPTN 071 (PopART): A Cluster-Randomized Trial of the Population Impact of an HIV Combination Prevention Intervention Including Universal Testing and Treatment: Mathematical Model. PLoS ONE 9(1): e84511. doi:10.1371/journal.pone.0084511 http://127.0.0.1:8081/plosone/article?id=info:doi/10.1371/journal.pone.0084511

Progam Results – Proposed Logic Model

SHIPP Chronology Leadership - Permanent Chief of Party in Place: Initial CoP rejected by USAID Dr. Farley Cleghorn of Futures as Interim CoP from contract award until May 2011 Dr. Kevin Bellis hired through stakeholder approved recruitment process and lasted until September 2012 Dr. Doris Macharia hired in November 2012 and performing at high level Partner/Subcontractor Performance Closure of Engender Health South Africa office in Year 1 Staff relocated within SHIPP and managed by Futures Amicable withdrawal of WRHI in Year 3 Expanding portfolio of PEPFAR work in HIV/AIDS treatment and implementation science Biomedical research orientation meant less interest in design and delivery of programmes at scale All activities subsumed under Futures Dr. Kevin Kelly left CADRE during Year 3 Need for research in later project years diminished SHIPP team capacity now available in research National and Provincial level agreement on key HIV prevention priorities elusive: Normative confusion on what sexual prevention activities to support in the National Strategic plan and what constitutes a responsive HIV prevention programme Enormous capacity issues at sub-district levels: Lack of information inability to plan, implement and manage programme activities, and mismatch between resources and expectations Finding Key Technical Staff High turnover in key technical staff and small pool of potential candidates at high cost Much effort and cost in recruitment and compensation Staff placed within SAG agencies at all levels “lost” to SHIPP management To address supply side barriers to postnatal care NSP 2012-2016 now being operationalized Combination HIV prevention will Improve service delivery models at local level, help to define action plans, and improve supply of prevention services Community based service delivery model that can address social, financial, and cultural barriers will improve demand and help shift community cultural norms SHIPP team now at full capacity in Year 4 Structure and functioning of team matches the scope of work Staff placed within four line ministries, SANAC and in 13 sub-districts Integrated team providing technical assistance in combination prevention and building capacity for more and better prevention services

SHIPP Mid-term Evaluation Key Reccomendations Scale up alternative LEAP process such as the DPSA’s Local Assessment Model based on KYE/KYR to inform optimal HIV combination packages at the local level Build on the capacity developed for DACs, LACs and WACs to enable them to identify, implement, monitor, and coordinate optimal HIV prevention packages In collaboration with SAG operationalize combination prevention packages for the SHIPP-supported districts based on an understanding of the local epidemic Support the demonstration of optimal combination HIV prevention packages in geographical areas where SHIPP/SAG has generated local epidemic information based on the Local Epidemic Assessment Model accepted in SA.

What more do we need to know? How do we prioritize non-biomedical interventions based on the evidence? How do these interventions combine with accepted biomedical interventions into coherent programming? How do we construct programmes at district/sub-district/community level so that these roll up into scale for impact?

Addressing the Implementation Science Gap Local Epidemic Assessment for Prevention (LEAP): An excel-based tool developed by the Health Policy Project & SHIPP that uses mathematical modeling (Impact matrix) to convert different intervention scenarios into changes in the incidence and prevalence of a local HIV epidemic LEAP distributes the relevant population by geography and risk groups and allows the user to Attribute different risk behaviors to these risk groups Develop interventions for specifically for key populations and target interventions for the general population by geography

LEAP – Population Risk Groups

LEAP in Mozambique Beira is an MOH priority district in Central Mozambique for both prevention and treatment interventions Located in a province with an estimated 15% HIV prevalence City population mostly divided into urban and peri-urban areas Focal point in the Central Transport Corridor District level data available: Demographic Behavioral Epidemiologic Programmatic

Using LEAP in Beira, Mozambique Policymakers using LEAP are be able to determine: Impact of combinations of interventions on HIV prevalence and incidence Most effective package of interventions based on: Type of interventions used (ie ART, VMMC, Community Mobilization, GBV programs) Tailored coverage for the general population, via geography Tailored coverage for key populations Most cost-effective interventions Develop an evidence-based package of interventions tailored to the local context Assess as they go

HIV Incidence by Year & Scenario Incidence per year as % of susceptible population 15-64 Ulundi: Max. 0.7% (Status Quo) Region G: Max. 0.8% (Status Quo) Min. 0.4% (New Combination) Min. 0.6% (New Combination)

Copyright © 2015 American Medical Association. All rights reserved. From: Human Immunodeficiency Virus Transmission at Each Step of the Care Continuum in the United States JAMA Intern Med. Published online February 23, 2015. doi:10.1001/jamainternmed.2014.8180 Figure Legend: Estimated Number of Human Immunodeficiency Virus (HIV) Transmissions Along the HIV Care ContinuumART indicates antiretroviral therapy; MSM-IDU, male-to-male sexual contact and injection drug use. Retained in care is defined as attending at least 1 visit with a medical care provider from January to April 2009. Viral suppression is defined as the most recent viral load documented as undetectable or 200 copies/mL or less. In A, error bars represent 95% simulation intervals. In D, estimates for persons 13 to 24 years old were not calculated because the Medical Monitoring Project and the National HIV Behavioral Surveillance System collect data only on persons 18 years or older, and the base population size estimated from the National HIV Surveillance System prevalence could not be determined by smaller age strata owing to sample size limitations. Date of download: 2/24/2015 Copyright © 2015 American Medical Association. All rights reserved.

Conclusions While results from specific combination trials in specific settings are forthcoming, countries and programs have enough information to implement combination programs for HIV prevention today. There is enough of an evidence base, tools, and solutions to support HIV prevention programs. Research and analytical technical assistance can provide continuing guidance to refine such programs to get to the goal of zero HIV transmission.