Outline

1. The population impact of ART scale-up on the risk of new HIV infection in rural KwaZulu-Natal, South AfricaFrank TanserPresentation at IAS, Kuala Lampur02 July 2013

2. Outline • Background • ART coverage and risk of HIV acquisition • Population viral load

3. 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

4. Study setting • Adult HIV prevalence 24% • High levels of unemployment and poverty • Zulu-speaking population • Former homeland under apartheid

5. The Africa Centre Africa Centre for Health and Population Studies

6. Adult life expectancy over time 13,060 deaths among 101,286 individuals aged 15 years and older, contributing a total of 651,350 person-years of follow-up time Bor, Herbst, Newell, and BärnighausenScience 2013

7. HIV incidence by age and sex 2004-2010 Females Males Tanser, Bärnighausen, Newell CROI 2011

8. Spatial clustering of new HIV infections Tanser et al CROI. Boston, MA; 2011.

9. Outline • Background • ART coverage and risk of HIV acquisition • Population viral load

10. Population-based HIV surveillance • Since 2003: Population-based HIV surveillance • Longitudinal, dynamic cohort • Entire adult population living in a contiguous geographical area of 438 km2 under surveillance • Annual rounds • 75% of those observed to be HIV-uninfected subsequently retest • All individuals geo-located Tanser, Hosegood, Bärnighausen et al. International Journal of Epidemiology 2007

11. ART coverage of all HIV-infected individuals 2004-2011 Tanser, Bärnighausen, Grapsa, Zaidi& Newell Science 2013

12. Population impact of ART coverage on risk of HIV acquisition (2004-2012) Survival analysis > 17,000 HIV-negative individuals followed-up for HIV acquisition over 60,558 person-years 1,573 HIV sero-conversions Time- (and space-) varying demographic, sexual behavior, economic and geographic controls, including HIV prevalence p=0.171 P<0.0001 p<0.0001 P<0.0001 Adjusted for age, sex, community-level HIV prevalence, urban vs. rural locale, marital status, >1 partner in last 12 months, and household wealth index

13. Population impact of condom use on risk of HIV acquisition (2005-2011) Adjusted for age, sex, community-level HIV prevalence, urban vs. rural locale, marital status, >1 partner in last 12 months, and household wealth index Tanser et al, Science, 2013

14. Conclusion • We find continued reductions in risk of acquiring HIV infection with increasing ART coverage in this typical rural sub-Saharan African setting • However, there is evidence of a “reduction saturation” effect (at coverage of >40%) under treatment guidelines of <350 CD4+ cells/µl

15. Outline • Background • ART coverage and risk of HIV acquisition • Population viral load

16. 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.

17. Figure 1 CVC as a measure for assessment of HIV treatment as prevention Miller, Powers, Smith et al Lancet Infectious Diseases 2013

18. CVC 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

19. Objectives • 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 • Assess the degree to which different population viral load summary measures highlight known areas of high incidence • (Establish the degree to which different population viral load summary measures predict future risk of new HIV infection in uninfected individuals)

20. Methods • All 2,456 individuals testing positive in the population-based HIV testing conducted in 2011 • 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)

21. Viral load distribution Median viral load = 6428 copies per ml

22. Geometric mean population viral load Copies /ml

23. Prevalence of unsuppressed viral load Prevalence (%)

24. Adjusted HIV acquisition hazard by prevalence category Adjusted for age, sex, community-level HIV prevalence, urban vs. rural locale, marital status, >1 partner in last 12 months, and household wealth index

25. Population prevalence of detectable virus (PPDV) Prevalence(%)

26. 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

27. Acknowledgements • The members of the community in Hlabisa sub-district who gave their time to this research • Staff of the Africa Centre for Health and Population Studies and the Hlabisa HIV Care and Treatment Programme • Colleagues at Africa Centre (Marie-Louise Newell, Till Bärnighausen, Tulio de Oliveira,KobusHerbst, Colin Newell, Jacob Bor, JafferZaidi and many more) • Funding • Wellcome Trust (Africa Centre for Health and Population Studies) • National Institutes of Health grants R01 HD058482-01 and 1R01MH083539-01