The population impacts of ART scale-up

in rural KwaZulu-Natal, South Africa: Results from the Africa Centre’s

population cohort

Frank Tanser

Presentation at 8th International Workshop on HIV Treatment, Pathogenesis and Prevention Research in Resource-Poor Settings, Lusaka

6th May 2014

Outline

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

Global ART scale-up

UNAIDS Report on the Global AIDS Epidemic 2012; WHO Universal Access Report 2013; Aaron Motsoaledi 2012

South Africa has the worldwide largest

absolute number of patients on ART,

>1.6 million by some estimates

Study setting

• Adult HIV prevalence 24%

• High levels of unemployment and poverty

• Zulu-speaking population

• Former homeland under apartheid

Africa Centre for Health and Population Studies

The Africa Centre

Bor, Herbst, Newell, and Bärnighausen Science 2013

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

HIV incidence by age and sex 2004-2010

0

0.01

0.02

0.03

0.04

0.05

0.06

0.07

0.08

0.09

0.1

0 20 40 60 80 100

HIV

Inci

denc

e (p

er Y

ear)

Age (Years)

00.010.020.030.040.050.060.070.080.09

0.1

0 20 40 60 80 100H

IV In

cid

en

ce (

pe

r ye

ar)

Age (years)

Females Males

Tanser, Bärnighausen, Newell CROI 2011

Spatial clustering of

new HIV infections

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 HIV-uninfected subsequently retest

– All individuals geo-located

Tanser, Hosegood, Bärnighausen et al. International Journal of Epidemiology 2007

Tanser, Bärnighausen, Grapsa, Zaidi & Newell Science 2013

ART coverage of all HIV-infected individuals 2004-2011

26237

26232

26241

26238 26233

26235

26240

26236

26239 26234

26231

26243

26242

26244

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

0

0,2

0,4

0,6

0,8

1

1,2

<10% 10-20% 20-30% 30-40% 40-50% >50%

Adj

uste

d H

azar

d ra

tio

Proportion of all HIV positive people receiving ART

p=0.004

P<0.0001 p<0.0001

P<0.0001

p=0.171

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

Population impact of ART coverage on risk of HIV acquisition (2004-2012)

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 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

Miller, Powers, Smith et al Lancet Infectious Diseases 2013

CVL as a measure for assessment of HIV treatment as prevention

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 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)

01.

0e-0

62.

0e-0

63.

0e-0

6D

ensi

ty

0 2000000 4000000 6000000 8000000 10000000VL Result (copies/ml)

Viral load distribution

Median viral load = 6428 copies per ml

Geometric mean population viral load

Copies /ml

Prevalence of unsuppressed viral load

Prevalence (%)

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 • 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,Kobus Herbst, Colin Newell, Jacob Bor, Jaffer Zaidi and many more)

• Funding − Wellcome Trust (Africa Centre for Health and Population

Studies) − National Institutes of Health grants R01 HD058482-01 and

1R01MH083539-01