Changes in population-level HIV RNA distribution one year after implementation of key components of an HIV ‘test and treat’ strategy in rural Uganda Vivek Jain, 1,2* Dalsone Kwarisiima, 2,3 Teri Liegler, 1 Tamara D. Clark, 1,2 Gabriel Chamie, 1,2 Jane Kabami, 2 Douglas Black, 1,2 Gideon Amanyire, 2,3 Dathan Byonanebye, 2,3 Elvin H. Geng 1,2 Harsha Thirumurthy, 2,4 Maya L. Petersen, 2,5 Edwin D. Charlebois, 2,6 Moses R. Kamya, 2,7 Diane V. Havlir, 1, and the SEARCH Collaboration HIV/AIDS Division, University of California, San Francisco (UCSF), USA Makerere University-UCSF Research Collaboration, Kampala, Uganda XIX International AIDS Conference, Washington DC, USA, July 24, 2012

Introduction SEARCH Collaboration is evaluating components of a ‘test and treat’ strategy for HIV in rural East Africa Assessment of population-level HIV RNA metrics is an important part of evaluating real-world effectiveness of test and treat strategies –VL suppression reflects effectiveness of entire cascade of care from HIV diagnosis to linkage to treatment to suppression –VL distribution of a population can provide insight into transmission

Study Setting Rural southwestern Uganda, HIV prevalence 8% Chamie et al., IAC 2012, Abstract #MOAE0103 Jain et al., IAC 2012, Abstract #TUPE081 5 day HIV testing campaign (n=4,343 persons) 74% adult participation HIV prevalence 7.8% 46% of HIV+ new diagnosis May 2011October 2011 Community Health Campaign Uganda MOH ART Revision (CD4 250  350) ART Availability regardless of CD4 via EARLI study (n=200 patients)

Objective Describe population HIV RNA metrics before and after test and treat building blocks initiated –Compare 2012 population HIV RNA distribution to 2011 Community Health Campaign Uganda MOH ART Revision (CD4 250  350) May 2011October 2011May 2012 ART Availability regardless of CD4 via EARLI study (n=200 patients) Community Health Campaign #2

Methods Health Campaigns: Kakyerere Parish May 2011/May 2012 CHC-1: 4,343 individuals screened over 5 days –Anonymous registration CHC-2: 4,872 individuals screened over 5 days –Non-anonymous registration Fingerprick-based viral load testing at CHC-1 and CHC-2 Jain et al., CROI 2012, Abstract 143LB HIV-1 RT-PCR (Abbott)

Population HIV RNA Metrics In HIV+ persons: multiple population RNA metrics 1.Proportion with undetectable VL 2.Median VL / IQR 3.Mean log(VL) level / geometric mean VL 4.Arithmetic mean VL Evaluation framework: population-based vs. clinic- based –CVL: clinic based; imputation for missing individuals –CHC approach: direct population measurement

CHC-1 and CHC-2 Results CHC CHC Total individuals screened4,3434,872 Parish adults screened2,2822,271 Community Participation (% of Parish adults) 74%72% Median age (IQR), years19 (9-38)20 (9-35) Gender, % male35% male45% male Adult HIV Prevalence HIV+ adults/Total adults, (%) 179/2282 (7.8%) 210/2271 (9.4%) Previously undiagnosed HIV, %46%in progress VL assayed n, (% of HIV+ adults)165/179 (92%)210/210 (100%) Chamie et al., IAC 2012, Abstract #MOAE0103

Decrease in Measured Population RNA Sample representation of community High community coverage, gender imbalance, other forces at work Identification and assessment of VL in individuals who did not participate in campaign 2011 CHC-1 (165 HIV+ adults) 2012 CHC-2 (210 HIV+ adults) Undetectable VL, n (%), 95% CI 62 (37%) (30%-45%) 115 (55%) (48%-62%) VL ,000 copies/mL, n (%)40 (24%)48 (23%) VL 10, ,000 copies/mL, n (%)42 (25%)40 (19%) VL >100,000 copies/mL, n (%)21 (13%)7 (3%) Median VL (IQR), copies/mL 2,185 (<486—33,045) <486 (<486—7,903) Mean log(VL) (95% CI), copies/mL 3.62 log (3.46—3.78 log) 3.20 log (3.09—3.31 log)

Landscape of Population Viral Load Assessments: Resource-Limited and Resource-Rich Settings Moving towards true population estimates in resource-limited settings where VL not part of routine clinical care CHC-Based RNA MetricsCommunity Viral Load MetricsUS 2011 Uganda2012 UgandaVancouverSFWash., DCCDC Undetectable VL n (%) 62 ( 37% )115 ( 55% ) 61% (VL<500, 2009) 78% (VL<75, 2008) 57% (VL<500, 2008) 28% Median VL (IQR), c/mL 2185 (<486—33,045) <486 (<486—7,903) < Mean log(VL) (95% CI), c/mL 3.62 log (3.46—3.78 log) 3.20 log (3.09—3.31 log) --- Arithmetic mean VL c/mL 64,06412, ,34833, Montaner, JSG et al., Lancet 2010; Das et al. PLoS ONE 2010; Castel A et al., AIDS 2011

Summary Assessed population HIV RNA levels before and after test and treat components initiated in a rural Ugandan district : –community-wide health campaigns to diagnose HIV and link to care –increased government access to ART –ART for persons with CD4>350 Population levels of HIV RNA lower in 2012: –higher proportion undetectable VL –lower median VL –lower geometric mean VL –fewer individuals with VL>100,000 c/mL

Acknowledgements SEARCH Collaboration Residents of Kakyerere Parish, Mbarara, Uganda Kakyerere Parish Local Councilors Uganda Ministry of Health Geoff Lavoy, MU-UCSF