INA-RESPOND Test and Treat Study Dr. M. Karyana, MPH Pusat Teknologi Terapan Kesehatan dan Epidemiologi Klinik, Badan Litbang Kesehatan – Kementerian Kesehatan RI Jakarta, 28 October 2014

Global AIDS response – first 25 years First cases of unusual immune deficiency are identified among gay men in the USA June 1981 First regimen to reduce MTCT of HIV Global Fund to fight AIDS, TB and Malaria Acquired Immune Deficiency Syndrome (AIDS) defined WHO and UNAIDS launch the "3 x 5" initiative Millions HAART launched 50 45 40 35 30 25 20 15 10 5 A heterosexual AIDS epidemic is revealed in Africa Brazil becomes the first developing country to provide ART HIV identified as cause of AIDS May 1983 The first HIV antibody test becomes available Global Network of People living with HIV/AIDS (GNP+) The WHO launches the Global Programme on AIDS President Bush announces PEPFAR The first therapy for AIDS - zidovudine/ AZT - is approved for use in the USA The UN General Assembly Special Session on HIV/AIDS UNAIDS created 2010 International AIDS Conference in Durban People living with HIV 1980 ‘81 ‘82 ‘83 ‘84 ‘85 ‘86 ‘87 ‘88 ‘89 ‘90 ‘91 ‘92 ‘93 ‘94 ‘95 ‘96 ‘97 ‘98 ‘99 ‘00 ‘01 ‘02 ‘03 ‘04 ‘05 The chronology above summarizes the ‘BIG Picture’ of AIDS – from the UNAIDS website Source: UNAIDS 2008 2

Source: UNAIDS Global Report 2014 Global number of people living with HIV & HIV-related deaths: Changes post-2005 Source: UNAIDS Global Report 2014

Top 20 countries: People living with HIV Zambia South Africa Nigeria India Kenya Mozambique 14.7 million = 42% Uganda Tanzania Zimbabwe USA Zambia 21.5 million = 61% Malawi China Ethiopia Russia Brazil 25.6 million = 73% Indonesia Cameroon D.R.Congo Thailand Cote d’Ivoire 28 million = 80% Source: UNAIDS Global Report 2014

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 , NEJM 2012 (Couples) Paxton L, NEJM 2012 (Heterosexuals) Choopanya K, Lancet 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 Treatment for prevention Cohen M, NEJM, 2011 Donnell D, Lancet 2010 Tanser, Science 2013 Behavioural Intervention Note: PMTCT, Screening transfusions, Harm reduction, Universal precautions, etc. have not been included – this is on sexual transmission

Clinical trial evidence for preventing HIV transmission – July 2013 Effect size (95%CI) Prevention in IDUs Bangkok Tenofovir Study - Daily oral PrEP for IDUs 49% (10; 72) HPTN 052 - ART for prevention 96% (73; 99) PartnersPrEP - Daily PrEP for discordant couples 73% (49; 85) TDF2 - Daily PrEP for heterosexual men and women 62% (22; 84) Medical male circumcision 54% (38; 66) Sexual transmission prevention iPrEX - Daily PrEP for MSM 44% (15; 63) Mwanza - STD treatment 42% (21; 58) CAPRISA 004 - Coital microbicide for women 39% (6; 60) RV144 - HIV vaccine 31% (1; 51) MTN 003 - Daily microbicide for women 15% (-21; 40) FEM-PrEP - Daily oral PrEP for women 6% (-52; 41) -60 -20 20 40 60 80 100 Effectiveness (%) Source: adapted from Abdool Karim SS. Lancet 2013

Audience with the Minister of Health

Study Title Indonesia Prevention of HIV and AIDS Transmission by Increasing Testing and Prompt Treatment

Research Question “Does a strategy of combination HIV prevention including universal HIV testing and treatment reduce HIV transmission (incidence) at community level?”

Hypothesis Universal voluntary HIV testing with appropriate combination prevention offered to all those testing HIV negative - in addition to immediate ART for all those testing HIV positive - will have a substantial impact on HIV incidence at population level

Lancet 2009 373: 48-57

Why is a Study Needed? Not known whether a UTT intervention can be delivered with high acceptability Many uncertainties in model parameters Population-level impact of intervention package is not known A rigorously designed study can measure the costs and benefits of this strategy and provide reliable evidence on cost-effectiveness for health policy makers

Design Issues What should the combination prevention package contain? HCT- universal uptake Linkage to care and provision of ART Sexual risk reduction PMTCT STI TB What scenarios would be useful to policy makers? Universal test and treat Vs current Costs of each Delivery under routine programmatic conditions as far as possible

Study Design

Study Coverage

Measuring HIV Incidence HIV incidence will be estimated by assessing HIV seroconversion in a longitudinal cohort Advantages Gold standard approach for HIV incidence estimation Uses routine HIV test methods Provides interim and cumulative incidence estimates Cohort allows for measurement of other indicators Disadvantages Requires longitudinal cohort follow-up Impacted by loss-to-follow up, including differential loss to follow-up Complex sampling is needed to ensure that the cohort reflects the population as a whole

Intervention Package Health centre Universal testing: annual door-to-door HCT Follow-up on referral Support for: Retention in care Adherence to treatment CHiPs: Community HIV-care Providers PMTCT: Prevention of Mother to Child Transmission TB: Tuberculosis STI: Sexually Transmitted Infections Service promotion and referral for - HIV care for HIV +ve including PMTCT - TB - STI Universal treatment for HIV +ve irrespective of CD4 count Facilitated by CHiPs

What is the influence of process parameters? efficacy of ART in blocking transmission treatment drop-out/failure Relative reduction in 3-year HIV incidence in arms A and B Linear model uptake of testing, ART Effect of counselling on infectivity % sex acts with partners from other communities Delays in linkage to care

Conclusions This study will use a cohort measure of HIV incidence to assess the effectiveness of a package of combination HIV prevention including a “universal test and treat” approach Adoption of new consolidated WHO guidelines should only moderately affect ability to detect differences between arms in the study Primary outcome mostly depends on Community-level changes in behaviours Efficacy of ART in blocking transmission (adherence) Uptake of HIV testing and treatment

Acknowledgement Supported by: The National Institute of Allergy and Infectious Diseases (NIAID), the U.S. National Institutes of Health (NIH) National Institutes of Health Research and Development (NIHRD), the Indonesia Ministry of Health

THANK YOU TERIMA KASIH MATUR SUKSMA MATUR SUWUN HATUR NUHUN