Frank Tanser

Cohort Profile: Africa Centre Demographic Information System (ACDIS) and population-based HIV survey

The health and demography of the South African population has been undergoing substantial changes as a result of the rapidly progressing HIV epidemic. Researchers at the University of KwaZulu-Natal and the South African Medical Research Council established The Africa Centre for Health and Population Studies in 1997 funded by a large core grant from The Wellcome Trust, UK. Given the urgent need for high quality longitudinal data with which to monitor these changes, and with which to evaluate interventions to mitigate impact, a demographic surveillance system (DSS) was established in a rural South African population facing a rapid and severe HIV epidemic. 1 The DSS, referred to as the Africa Centre Demographic Information System (ACDIS), started in 2000. In 2003, population-based HIV testing (also funded by the Wellcome Trust, UK) was started in ACDIS through annual surveys. In this article, we seek to describe the most salient features of ACDIS and the population-based HIV cohort and briefly present some of the most important results to date.

Adult mortality and antiretroviral treatment roll-out in rural KwaZulu-Natal, South Africa

OBJECTIVE To investigate trends in adult mortality in a population serviced by a public-sector antiretroviral therapy (ART) programme in rural South Africa using a demographic surveillance system. METHODS Verbal autopsies were conducted for all 7930 deaths observed between January 2000 and December 2006 in a demographic surveillance population of 74,500 in the Umkhanyakude district of northern KwaZulu-Natal province, South Africa. Age-standardized mortality rate ratios (SMRRs) were calculated for adults aged 25 to 49 years, the group most affected by HIV, for the 2 years before 2004 and the 3 subsequent years, during which ART had been available. FINDINGS Between 2002-2003 (the period before ART) and 2004-2006 (the period after ART), HIV-related age-standardized mortality declined significantly, from 22.52 to 17.58 per 1000 person-years in women 25-49 years of age (P < 0.001; SMRR: 0.780; 95% confidence interval, CI: 0.691-0.881), and from 26.46 to 18.68 per 1000 person-years in men 25-49 years of age (P < 0.001; SMRR: 0.706; 95% CI: 0.615-0.811). On sensitivity analysis the results were robust to the possible effect of misclassification of HIV-related deaths. CONCLUSION Overall population mortality and HIV-related adult mortality declined significantly following ART roll-out in a community with a high prevalence of HIV infection. A clear public health message of the benefits of treatment, as revealed by these findings, should be part of a multi-faceted strategy to encourage people to find out their HIV serostatus and seek care.

Localized spatial clustering of HIV infections in a widely disseminated rural South African epidemic

BACKGROUND South Africa contains more than one in seven of the worlds HIV-positive population. Knowledge of local variation in levels of HIV infection is important for prioritization of areas for intervention. We apply two spatial analytical techniques to investigate the micro-geographical patterns and clustering of HIV infections in a high prevalence, rural population in KwaZulu-Natal, South Africa. METHODS All 12,221 participants who consented to an HIV test in a population under continuous demographical surveillance were linked to their homesteads and geo-located in a geographical information system (accuracy of <2 m). We then used a two-dimensional Gaussian kernel of radius 3 km to produce robust estimates of HIV prevalence that vary across continuous geographical space. We also applied a Kulldorff spatial scan statistic (Bernoulli model) to formally identify clusters of infections (P < 0.05). RESULTS The results reveal considerable geographical variation in local HIV prevalence (range = 6-36%) within this relatively homogenous population and provide clear empirical evidence for the localized clustering of HIV infections. Three high-risk, overlapping spatial clusters [Relative Risk (RR) = 1.34-1.62] were identified by the Kulldorff statistic along the National Road (P < or = 0.01), whereas three low risk clusters (RR = 0.2-0.38) were identified elsewhere in the study area (P < or = 0.017). CONCLUSIONS The findings show the existence of several localized HIV epidemics of varying intensity that are partly contained within geographically defined communities. Despite the overall high prevalence of HIV in many rural South African settings, the results support the need for interventions that target socio-geographic spaces (communities) at greatest risk to supplement measures aimed at the general population.

Dramatic increase in HIV prevalence after scale-up of antiretroviral treatment.

Objectives:To investigate HIV prevalence trends in a rural South African community after the scale-up of antiretroviral treatment (ART) in 2004. Methods:We estimated adult HIV prevalence (ages 15–49 years) using data from a large, longitudinal, population-based HIV surveillance in rural KwaZulu-Natal, South Africa, over the period from 2004 (the year when the public-sector ART scale-up started) to 2011. We control for selection effects due to surveillance nonparticipation using multiple imputation. We further linked the surveillance data to patient records from the local HIV treatment program to estimate ART coverage. Results:ART coverage of all HIV-infected people in this community increased from 0% in 2004 to 31% in 2011. Over the same observation period adult HIV prevalence increased steadily from 21 to 29%. The change in overall HIV prevalence is nearly completely explained by an increase of HIV-infected people receiving ART, and it is largely driven by increases in HIV prevalence in women and men older than 24 years. Conclusion:The observed dramatic increase in adult HIV prevalence can most likely be explained by increased survival of HIV-infected people due to ART. Future studies should decompose HIV prevalence trends into HIV incidence and HIV-specific mortality changes to further improve the causal attribution of prevalence increases to treatment success rather than prevention failure.

High HIV incidence in a community with high HIV prevalence in rural South Africa: Findings from a prospective population-based study.

Objectives: To measure HIV incidence in a rural area of South Africa with high HIV prevalence and to analyze risk factors for acquisition of HIV using a prospective population-based cohort study. Methods: Data from two rounds (2003–2005) of a large prospective population-based HIV survey in rural KwaZulu-Natal were used to calculate HIV incidence by sex and 5-year age group. Multiple imputations (MI) were used to adjust for selection effects and risk factors for acquiring HIV were examined in Weibull multiple regression. Results: During 5253 person-years at risk, 170 individuals became seropositive. The crude HIV incidence rate per 100 person-years was 3.8 [95% confidence interval (CI), 3.2–4.6] in women aged 15–49 years and 2.3 (95% CI, 1.8–3.1) in men aged 15–54 years. MI significantly increased the HIV incidence rates both in women and men [7.9/100 person-years (95% CI, 7.4–8.4) and 5.1/100 person-years (95% CI 4.1–6.2), respectively]. When holding other factors constant in Weibull multiple regression, the hazard of HIV seroconversion was approximately twice as high in people who were currently unmarried but had a partner than among people who were currently married (P < 0.001) and increased with increasing distance from a government health clinic (P = 0.051) and decreasing distance from a primary road (P = 0.002). Conclusion: In this high HIV prevalence community in rural South Africa HIV incidence is very high. The present focus on antiretroviral treatment needs to be balanced with a renewed emphasis on HIV prevention for both sexes.

In A Study Of A Population Cohort In South Africa, HIV Patients On Antiretrovirals Had Nearly Full Recovery Of Employment

Antiretroviral therapy for HIV may have important economic benefits for patients and their households. We quantified the impact of HIV treatment on employment status among HIV patients in rural South Africa who were enrolled in a public-sector HIV treatment program supported by the Presidents Emergency Plan for AIDS Relief. We linked clinical data from more than 2,000 patients in the treatment program with ten years of longitudinal socioeconomic data from a complete community-based population cohort of more than 30,000 adults residing in the clinical catchment area. We estimated the employment effects of HIV treatment in fixed-effects regressions. Four years after the initiation of antiretroviral therapy, employment among HIV patients had recovered to about 90 percent of baseline rates observed in the same patients three to five years before they started treatment. Many patients initiated treatment early enough that they were able to avoid any loss of employment due to HIV. These results represent the first estimates of employment recovery among HIV patients in a general population, relative to the employment levels that these patients had prior to job-threatening HIV illness and the decision to seek care. There are large economic benefits to HIV treatment. For some patients, further gains could be obtained from initiating antiretroviral therapy earlier, prior to HIV-related job loss.

The impact of antiretroviral treatment on the age composition of the HIV epidemic in sub-Saharan Africa

Introduction:Antiretroviral treatment (ART) coverage is rapidly expanding in sub-Saharan Africa (SSA). Based on the effect of ART on survival of HIV-infected people and HIV transmission, the age composition of the HIV epidemic in the region is expected to change in the coming decades. We quantify the change in the age composition of HIV-infected people in all countries in SSA. Methods:We used STDSIM, a stochastic microsimulation model, and developed an approach to represent HIV prevalence and treatment coverage in 43 countries in SSA, using publicly available data. We predict future trends in HIV prevalence and total number of HIV-infected people aged 15–49 years and 50 years or older for different ART coverage levels. Results:We show that, if treatment coverage continues to increase at present rates, the total number of HIV-infected people aged 50 years or older will nearly triple over the coming years: from 3.1 million in 2011 to 9.1 million in 2040, dramatically changing the age composition of the HIV epidemic in SSA. In 2011, about one in seven HIV-infected people was aged 50 years or older; in 2040, this ratio will be larger than one in four. Conclusion:The HIV epidemic in SSA is rapidly ageing, implying changing needs and demands in many social sectors, including health, social care, and old-age pension systems. Health policymakers need to anticipate the impact of the changing HIV age composition in their planning for future capacity in these systems.

Evaluation of the impact of immediate versus WHO recommendations-guided antiretroviral therapy initiation on HIV incidence: the ANRS 12249 TasP (Treatment as Prevention) trial in Hlabisa sub-district, KwaZulu-Natal, South Africa: study protocol for a cluster randomised controlled trial

BackgroundAntiretroviral therapy (ART) suppresses HIV viral load in all body compartments and so limits the risk of HIV transmission. It has been suggested that ART not only contributes to preventing transmission at individual but potentially also at population level. This trial aims to evaluate the effect of ART initiated immediately after identification/diagnosis of HIV-infected individuals, regardless of CD4 count, on HIV incidence in the surrounding population. The primary outcome of the overall trial will be HIV incidence over two years. Secondary outcomes will include i) socio-behavioural outcomes (acceptability of repeat HIV counselling and testing, treatment acceptance and linkage to care, sexual partnerships and quality of life); ii) clinical outcomes (mortality and morbidity, retention into care, adherence to ART, virologic failure and acquired HIV drug resistance), iii) cost-effectiveness of the intervention. The first phase will specifically focus on the trial’s secondary outcomes.Methods/designA cluster-randomised trial in 34 (2 × 17) clusters within a rural area of northern KwaZulu-Natal (South Africa), covering a total population of 34,000 inhabitants aged 16 years and above, of whom an estimated 27,200 would be HIV-uninfected at start of the trial. The first phase of the trial will include ten (2 × 5) clusters. Consecutive rounds of home-based HIV testing will be carried out. HIV-infected participants will be followed in dedicated trial clinics: in intervention clusters, they will be offered immediate ART initiation regardless of CD4 count and clinical stage; in control clusters they will be offered ART according to national treatment eligibility guidelines (CD4 <350 cells/μL, World Health Organisation stage 3 or 4 disease or multidrug-resistant/extensively drug-resistant tuberculosis). Following proof of acceptability and feasibility from the first phase, the trial will be rolled out to further clusters.DiscussionWe aim to provide proof-of-principle evidence regarding the effectiveness of Treatment-as-Prevention in reducing HIV incidence at the population level. Data collected from the participants at home and in the clinics will inform understanding of socio-behavioural, economic and clinical impacts of the intervention as well as feasibility and generalizability.Trial registrationClinicaltrials.gov: NCT01509508; South African Trial Register: DOH-27-0512-3974.

HIV incidence in rural South Africa: comparison of estimates from longitudinal surveillance and cross-sectional cBED assay testing.

Background The BED IgG-Capture Enzyme Immunoassay (cBED assay), a test of recent HIV infection, has been used to estimate HIV incidence in cross-sectional HIV surveys. However, there has been concern that the assay overestimates HIV incidence to an unknown extent because it falsely classifies some individuals with non-recent HIV infections as recently infected. We used data from a longitudinal HIV surveillance in rural South Africa to measure the fraction of people with non-recent HIV infection who are falsely classified as recently HIV-infected by the cBED assay (the long-term false-positive ratio (FPR)) and compared cBED assay-based HIV incidence estimates to longitudinally measured HIV incidence. Methodology/Principal Findings We measured the long-term FPR in individuals with two positive HIV tests (in the HIV surveillance, 2003–2006) more than 306 days apart (sample size n = 1,065). We implemented four different formulae to calculate HIV incidence using cBED assay testing (n = 11,755) and obtained confidence intervals (CIs) by directly calculating the central 95th percentile of incidence values. We observed 4,869 individuals over 7,685 person-years for longitudinal HIV incidence estimation. The long-term FPR was 0.0169 (95% CI 0.0100–0.0266). Using this FPR, the cross-sectional cBED-based HIV incidence estimates (per 100 people per year) varied between 3.03 (95% CI 2.44–3.63) and 3.19 (95% CI 2.57–3.82), depending on the incidence formula. Using a long-term FPR of 0.0560 based on previous studies, HIV incidence estimates varied between 0.65 (95% CI 0.00–1.32) and 0.71 (95% CI 0.00–1.43). The longitudinally measured HIV incidence was 3.09 per 100 people per year (95% CI 2.69–3.52), after adjustment to the sex-age distribution of the sample used in cBED assay-based estimation. Conclusions/Significance In a rural community in South Africa with high HIV prevalence, the long-term FPR of the cBED assay is substantially lower than previous estimates. The cBED assay performs well in HIV incidence estimation if the locally measured long-term FPR is used, but significantly underestimates incidence when a FPR estimate based on previous studies in other settings is used.

New approaches to spatially analyse primary health care usage patterns in rural South Africa

OBJECTIVE To develop indices to quantitatively assess and understand the spatial usage patterns of health facilities in the Hlabisa district of South Africa.