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Using longitudinal, population-based HIV surveillance to measure the real-world impacts of ART scale-up in KwaZuluNatal, South Africa Frank Tanser Presentation at IAS, Melbourne, Australia 22nd July 2014 Outline • Background • ART coverage and risk of HIV acquisition • Population viral load Global ART scale-up South Africa has the worldwide largest absolute number of patients on ART, >1.6 million by some estimates UNAIDS Report on the Global AIDS Epidemic 2012; WHO Universal Access Report 2013; Aaron Motsoaledi 2012 Hlabisa sub-district, with the Africa Centre surveillance area and the TasP trial area The Africa Centre Africa Centre for Health and Population Studies Adult life expectancy in years Adult life expectancy over time 60 13,060 deaths among 101,286 individuals aged 15 years and older, contributing a total of 651,350 personyears of followup time 55 50 45 2000 2002 2004 2006 2008 2010 Year Bor, Herbst, Newell, and Bärnighausen Science 2013 2012 HIV incidence by age and sex 2004-2010 Males 0.1 0.1 0.09 0.09 0.08 0.08 HIV Incidence (per year) HIV Incidence (per Year) Females 0.07 0.06 0.05 0.04 0.03 0.02 0.07 0.06 0.05 0.04 0.03 0.02 0.01 0.01 0 0 0 20 40 60 80 100 Age (Years) Tanser, Bärnighausen, Newell CROI 2011 0 20 40 60 Age (years) 80 100 •80% life-time risk of acquiring HIV Spatial clustering of new HIV infections Tanser et al CROI. Boston, MA; 2011. Distribution of sero-conversions Tanser et al CROI. Boston, MA; 2011. Outline • Background • ART coverage and risk of HIV acquisition • Population viral load Population-based HIV surveillance • Since 2003: Population-based HIV cohort – Longitudinal, dynamic cohort – Entire adult population living in a contiguous geographical area of 438 km2 eligible for testing – Annual rounds – 75% of those observed to be HIVuninfected subsequently retest – All individuals geo-located Tanser, Hosegood, Bärnighausen et al. International Journal of Epidemiology 2007 26236 26243 26235 26234 26244 26233 26239 26238 26237 26240 26242 26232 26231 26241 Population impact of ART coverage on risk of Survival analysis HIV acquisition (2004-2012) > 17,000 HIVnegative individuals followed-up for HIV acquisition over 60,558 person-years Adjusted Hazard ratio 1.2 1 0.8 p=0.171 1,573 HIV seroconversions 0.6 P<0.0001 p<0.0001 0.4 P<0.0001 p=0.004 0.2 0 <10% 10-20% 20-30% 30-40% 40-50% Proportion of all HIV positive people receiving ART >50% Time- (and space-) varying demographic, sexual behavior, economic and geographic controls, including HIV prevalence Adjusted for age, sex, community-level HIV prevalence, urban vs. rural locale, marital status, >1 partner in last 12 months, and household wealth index Conclusion • We find continued reductions in risk of acquiring HIV infection with increasing ART coverage in this typical rural subSaharan African setting • However, there is suggestion of a “reduction saturation” effect (at coverage of >40%) under treatment guidelines of <350 CD4+ cells/µl Outline • Background • ART coverage and risk of HIV acquisition • Population viral load Population/Community viral load • Proposed as: – an aggregate measure of the potential for ongoing HIV transmission within a community – as a surveillance measure for monitoring uptake and effectiveness of antiretroviral therapy. Figure 1 CVL as a measure for assessment of HIV treatment as prevention Miller, Powers, Smith et al Lancet Infectious Diseases 2013 CVL as a measure for assessment of HIV treatment as prevention “ The issue of selection bias [in community viral load] could be addressed with a population-based survey in a clearly defined target population of all people in a community, including those with and without known HIV infection” Miller, Powers, Smith et al Lancet Infectious Diseases 2013 Objectives 1. Asses whether viral loads in this population are randomly distributed in space or whether high or low viral loads tend to cluster in certain areas 2. Assess the degree to which different population viral load summary measures highlight known areas of high incidence 3. (Establish the degree to which different population viral load summary measures predict future risk of new HIV infection in uninfected individuals) Methods • All 2,456 individuals testing positive in a single round of the population-based HIV testing • Total number DBS specimens tested was 2,420 (36 specimens excluded due to being insufficient for testing). • Of these, 30% (726) were below the detectable limit of 1550 copies/ml (Viljoen et al, JAIDS 2010) 2.0e-06 Median viral load = 6428 copies per ml 0 1.0e-06 Density 3.0e-06 Viral load distribution 0 2000000 4000000 6000000 VL Result (copies/ml) 8000000 10000000 Geometric mean population viral load Copies /ml Population prevalence of detectable virus (PPDV) Prevalence(%) Conclusion • To measure transmission potential of a community, any viral load summary index must take into account the size of the uninfected population • Population prevalence of detectable virus (PPDV) successfully identified known areas of continued high HIV incidence • We propose the PPDV as a simple community-level index of transmission potential Acknowledgements We thank the field staff at the Africa Centre for Health and Population Studies at the University of KwaZulu-Natal, South Africa, for their work in collecting the data used in this study and the communities in the Africa Centre demographic surveillance area for their support and participation in this study. Co-authors Till Bärnighausen, Deenan Pillay Funding Frank Tanser & Till Bärnighausen were supported by grant 1R01-HD05848201 from the National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), USA. Core funding for the Africa Centre's Demographic Surveillance Information System (GR065377/Z/01/H) and Population-based HIV Survey (GR065377/Z/01/B) was received from the Welcome Trust, UK.