Antiretroviral Therapy and Mortality in Rural South Africa: A Comparison of Causal Modeling Approaches.
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SUBMITTER: Oldenburg CE
PROVIDER: S-EPMC6070080 | biostudies-other | 2018 Mar
REPOSITORIES: biostudies-other
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Antiretroviral Therapy and Mortality in Rural South Africa: A Comparison of Causal Modeling Approaches.
Oldenburg Catherine E CE Seage George R GR Tanser Frank F De Gruttola Victor V Mayer Kenneth H KH Mimiaga Matthew J MJ Bor Jacob J Bärnighausen Till T
American journal of epidemiology 20180801 8
Estimation of causal effects from observational data is a primary goal of epidemiology. The use of multiple methods with different assumptions relating to exchangeability improves causal inference by demonstrating robustness across assumptions. We estimated the effect of antiretroviral therapy (ART) on mortality in rural KwaZulu-Natal, South Africa, from 2007 to 2011, using 2 methods with substantially different assumptions: the regression discontinuity design (RDD) and inverse-probability-weigh ...[more]
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Project description:BackgroundUnderstanding the effects of socioeconomic disparities in health outcomes is important to implement specific preventive actions. We assessed socioeconomic disparities in mortality indicators in a rural South African population over the period 2001-13.MethodsWe used data from 21 villages of the Agincourt Health and socio-Demographic Surveillance System (HDSS). We calculated the probabilities of death from birth to age 5 years and from age 15 to 60 years, life expectancy at birth, and cause-specific and age-specific mortality by sex (not in children <5 years), time period, and socioeconomic status (household wealth) quintile for HIV/AIDS and tuberculosis, other communicable diseases (excluding HIV/AIDS and tuberculosis) and maternal, perinatal, and nutritional causes, non-communicable diseases, and injury. We also quantified differences with relative risk ratios and relative and slope indices of inequality.FindingsBetween 2001 and 2013, 10 414 deaths were registered over 1 058 538 person-years of follow-up, meaning the overall crude mortality was 9·8 deaths per 1000 person-years. We found significant socioecomonic status gradients for mortality and life expectancy at birth, with outcomes improving with increasing socioeconomic status. An inverse relation was seen for HIV/AIDS and tuberculosis mortality and socioeconomic status that persisted from 2001 to 2013. Deaths from non-communicable diseases increased over time in both sexes, and injury was an important cause of death in men and boys. Neither of these causes of death, however, showed consistent significant associations with household socioeconomic status.InterpretationThe poorest people in the population continue to bear a high burden of HIV/AIDS and tuberculosis mortality, despite free antiretroviral therapy being made available from public health facilities. Associations between socioeconomic status and increasing burden of mortality from non-communicable diseases is likely to become prominent. Integrated strategies are needed to improve access to and uptake of HIV testing, care, and treatment, and management of non-communicable diseases in the poorest populations.FundingWellcome Trust, South African Medical Research Council, and University of the Witwatersrand, South Africa.
| S-EPMC5559644 | biostudies-literature
Project description:BackgroundThe provision of highly active antiretroviral therapy (HAART) in resource-limited settings follows a public health approach, which is characterised by a limited number of regimens and the standardisation of clinical and laboratory monitoring. In industrialized countries doctors prescribe from the full range of available antiretroviral drugs, supported by resistance testing and frequent laboratory monitoring. We compared virologic response, changes to first-line regimens, and mortality in HIV-infected patients starting HAART in South Africa and Switzerland.Methods and findingsWe analysed data from the Swiss HIV Cohort Study and two HAART programmes in townships of Cape Town, South Africa. We included treatment-naïve patients aged 16 y or older who had started treatment with at least three drugs since 2001, and excluded intravenous drug users. Data from a total of 2,348 patients from South Africa and 1,016 patients from the Swiss HIV Cohort Study were analysed. Median baseline CD4+ T cell counts were 80 cells/mul in South Africa and 204 cells/mul in Switzerland. In South Africa, patients started with one of four first-line regimens, which was subsequently changed in 514 patients (22%). In Switzerland, 36 first-line regimens were used initially, and these were changed in 539 patients (53%). In most patients HIV-1 RNA was suppressed to 500 copies/ml or less within one year: 96% (95% confidence interval [CI] 95%-97%) in South Africa and 96% (94%-97%) in Switzerland, and 26% (22%-29%) and 27% (24%-31%), respectively, developed viral rebound within two years. Mortality was higher in South Africa than in Switzerland during the first months of HAART: adjusted hazard ratios were 5.90 (95% CI 1.81-19.2) during months 1-3 and 1.77 (0.90-3.50) during months 4-24.ConclusionsCompared to the highly individualised approach in Switzerland, programmatic HAART in South Africa resulted in similar virologic outcomes, with relatively few changes to initial regimens. Further innovation and resources are required in South Africa to both achieve more timely access to HAART and improve the prognosis of patients who start HAART with advanced disease.
| S-EPMC2443185 | biostudies-literature
Project description:OBJECTIVE:To explore the impact of expanded eligibility criteria for antiretroviral therapy (ART) on median CD4? cell count at ART initiation and early mortality on ART. METHODS:Analyses included all adults (?16 years) initiated on first-line ART between August 2004 and July 2012. CD4? cell count threshold 350 cells per microliter for all adults was implemented in August 2011. Early mortality was defined as any death within 91 days of ART initiation. Trends in baseline CD4? cell count and early mortality were examined by year (August to July) of ART initiation. Competing risks analysis was used to examine early mortality. RESULTS:A total of 19,080 adults (67.6% female) initiated ART. Median CD4? cell count at ART initiation was 110-120 cells per microliter over the first 6 years, increasing marginally to 145 cells per microliter in 2010-2011 and more significantly to 199 cells per microliter in 2011-2012. Overall, there were 875 deaths within 91 days of ART initiation; early mortality rate was 19.4 per 100 person-years [95% confidence interval (CI) 18.2 to 20.7]. After adjustment for sex, age, baseline CD4? cell count, and concurrent tuberculosis (TB), there was a 46% decrease in early mortality for those who initiated ART in 2011-2012 compared with the reference period 2008-2009 (subhazard ratio, 0.54; 95% CI: 0.41 to 0.71). CONCLUSIONS:Since the expansion of eligibility criteria, there is evidence of earlier access to ART and a significant reduction in early mortality rate in this primary health care programme. These findings provide strong support for national ART policies and highlight the importance of earlier ART initiation for achieving reductions in HIV-related mortality.
| S-EPMC3867341 | biostudies-literature
Project description:ObjectivesWe investigate the effect of immediate antiretroviral therapy (ART) eligibility on HIV incidence among HIV-uninfected household members.DesignRegression discontinuity study arising from a population-based cohort.MethodsHousehold members of patients seeking care at the Hlabisa HIV Treatment and Care Programme in rural KwaZulu-Natal South Africa between January 2007 and August 2011 with CD4 cell counts up to 350 cells/μl were eligible for inclusion if they had at least two HIV tests and were HIV-uninfected at the time the index patient linked to care (N = 4115). Regression discontinuity was used to assess the intention-to-treat effect of immediate versus delayed ART eligibility on HIV incidence among household members. Exploiting the CD4 cell count-based threshold rule for ART initiation (CD4 < 200 cells/μl until August 2011), we used Cox proportional hazards models to compare outcomes for household members of patients who presented for care with CD4 cell counts just above versus just below the ART initiation threshold.ResultsCharacteristics of household members of index patients initiating HIV care were balanced between those with an index patient immediately eligible for ART (N = 2489) versus delayed for ART (N = 1626). There were 337 incident HIV infections among household members, corresponding to an HIV incidence of 2.4 infections per 100 person-years (95% confidence interval 2.5-3.1). Immediate eligibility for treatment reduced HIV incidence in households by 47% in our optimal estimate (hazard ratio = 0.53, 95% confidence interval 0.30-0.96), and by 32-60% in alternate specifications of the model.ConclusionImmediate eligibility of ART led to substantial reductions in household-level HIV incidence.
| S-EPMC5832606 | biostudies-literature
Project description:BackgroundMortality in HIV-infected patients who have access to highly active antiretroviral therapy (ART) has declined in sub-Saharan Africa, but it is unclear how mortality compares to the non-HIV-infected population. We compared mortality rates observed in HIV-1-infected patients starting ART with non-HIV-related background mortality in four countries in sub-Saharan Africa.Methods and findingsPatients enrolled in antiretroviral treatment programmes in Côte d'Ivoire, Malawi, South Africa, and Zimbabwe were included. We calculated excess mortality rates and standardised mortality ratios (SMRs) with 95% confidence intervals (CIs). Expected numbers of deaths were obtained using estimates of age-, sex-, and country-specific, HIV-unrelated, mortality rates from the Global Burden of Disease project. Among 13,249 eligible patients 1,177 deaths were recorded during 14,695 person-years of follow-up. The median age was 34 y, 8,831 (67%) patients were female, and 10,811 of 12,720 patients (85%) with information on clinical stage had advanced disease when starting ART. The excess mortality rate was 17.5 (95% CI 14.5-21.1) per 100 person-years SMR in patients who started ART with a CD4 cell count of less than 25 cells/microl and World Health Organization (WHO) stage III/IV, compared to 1.00 (0.55-1.81) per 100 person-years in patients who started with 200 cells/microl or above with WHO stage I/II. The corresponding SMRs were 47.1 (39.1-56.6) and 3.44 (1.91-6.17). Among patients who started ART with 200 cells/microl or above in WHO stage I/II and survived the first year of ART, the excess mortality rate was 0.27 (0.08-0.94) per 100 person-years and the SMR was 1.14 (0.47-2.77).ConclusionsMortality of HIV-infected patients treated with combination ART in sub-Saharan Africa continues to be higher than in the general population, but for some patients excess mortality is moderate and reaches that of the general population in the second year of ART. Much of the excess mortality might be prevented by timely initiation of ART.
| S-EPMC2667633 | biostudies-literature
Project description:Expanded access to antiretroviral therapy (ART) using universal test and treat (UTT) has been suggested as a strategy to eliminate HIV in South Africa within 7 y based on an influential mathematical modeling study. However, the underlying deterministic model was criticized widely, and other modeling studies did not always confirm the study's finding. The objective of our study is to better understand the implications of different model structures and assumptions, so as to arrive at the best possible predictions of the long-term impact of UTT and the possibility of elimination of HIV.We developed nine structurally different mathematical models of the South African HIV epidemic in a stepwise approach of increasing complexity and realism. The simplest model resembles the initial deterministic model, while the most comprehensive model is the stochastic microsimulation model STDSIM, which includes sexual networks and HIV stages with different degrees of infectiousness. We defined UTT as annual screening and immediate ART for all HIV-infected adults, starting at 13% in January 2012 and scaled up to 90% coverage by January 2019. All models predict elimination, yet those that capture more processes underlying the HIV transmission dynamics predict elimination at a later point in time, after 20 to 25 y. Importantly, the most comprehensive model predicts that the current strategy of ART at CD4 count ?350 cells/µl will also lead to elimination, albeit 10 y later compared to UTT. Still, UTT remains cost-effective, as many additional life-years would be saved. The study's major limitations are that elimination was defined as incidence below 1/1,000 person-years rather than 0% prevalence, and drug resistance was not modeled.Our results confirm previous predictions that the HIV epidemic in South Africa can be eliminated through universal testing and immediate treatment at 90% coverage. However, more realistic models show that elimination is likely to occur at a much later point in time than the initial model suggested. Also, UTT is a cost-effective intervention, but less cost-effective than previously predicted because the current South African ART treatment policy alone could already drive HIV into elimination. Please see later in the article for the Editors' Summary.
| S-EPMC3805487 | biostudies-other
Project description:BACKGROUNDAntiretroviral therapy (ART) was highly efficacious in preventing human immunodeficiency virus (HIV) transmission in stable serodiscordant couples in the HPTN-052 study, a resource-intensive randomized controlled trial with near-perfect ART adherence and mutual HIV status disclosure among all participating couples. However, minimal evidence exists of the effectiveness of ART in preventing HIV acquisition in stable serodiscordant couples in "real-life" population-based settings in hyperendemic communities of sub-Saharan Africa, where health systems are typically resource-poor and overburdened, adherence to ART is often low, and partners commonly do not disclose their HIV status to each other.METHODSData arose from a population-based open cohort in KwaZulu-Natal, South Africa. A total of 17 016 HIV-uninfected individuals present between January 2005 and December 2013 were included. Interval-censored time-updated proportional hazards regression was used to assess how the ART status affected HIV transmission risk in stable serodiscordant relationships.RESULTSWe observed 1619 HIV seroconversions in 17 016 individuals, over 60 349 person-years follow-up time. During the follow-up period, 1846 individuals had an HIV-uninfected and 196 had an HIV-infected stable partner HIV incidence was 3.8/100 person-years (PY) among individuals with an HIV-infected partner (95% confidence interval [CI], 2.3-5.6), 1.4/100 PY (.4-3.5) among those with HIV-infected partners receiving ART, and 5.6/100 PY (3.5-8.4) among those with HIV-infected partners not receiving ART. Use of ART was associated with a 77% decrease in HIV acquisition risk among serodiscordant couples (adjusted hazard ratio, 0.23; 95% CI, .07-.80).CONCLUSIONSART initiation was associated with a very large reduction in HIV acquisition in serodiscordant couples in rural KwaZulu-Natal. However, this "real-life" effect was substantially lower than the effect observed in the HPTN-052 trial. To eliminate HIV transmission in serodiscordant couples, additional prevention interventions are probably needed.
| S-EPMC4967606 | biostudies-literature
Project description:ObjectiveThe vital status of patients lost to follow-up often remains unknown in antiretroviral therapy (ART) programmes in sub-Saharan Africa because medical records are no longer updated once the patient disengages from care. Thus, we aimed to assess the outcomes of patients lost to follow-up after ART initiation in north-eastern South Africa.MethodsUsing data from a rural area in north-eastern South Africa, we estimated the cumulative incidence of patient outcomes (i) after treatment initiation using clinical records, and (ii) after loss to follow-up (LTFU) using data from clients that have been individually linked to Agincourt Health and Demographic Surveillance System (AHDSS) database. Aside from LTFU, we considered mortality, re-engagement and migration out of the study site. Cox proportional hazards regression was used to identify covariates of these patient outcomes.ResultsBetween April 2014 and July 2017, 3700 patients initiated ART and contributed a total of 6818 person-years of follow-up time. Three years after ART initiation, clinical record-based estimates of LTFU, mortality and documented transfers were 41.0% (95% CI: 38.5-43.4%), 1.9% (95% CI 1.0-3.2%) and 0.1% (95% CI 0.0-0.9%), respectively. Among those who were LTFU, the cumulative incidence of re-engagement, out-migration and mortality at 3 years were 38.1% (95% CI 33.1-43.0%), 49.4% (95% CI 43.1-55.3%) and 4.7% (95% CI 3.5-6.2%), respectively. Pregnant or breastfeeding women, foreigners and those who initiated ART most recently were at an increased risk of LTFU.ConclusionLTFU among patients starting ART in north-eastern South Africa is relatively high and has increased in recent years as more asymptomatic patients have initiated treatment. Even though this tendency is of concern in light of the prevention of onwards transmission, we also found that re-engagement in care is common and mortality among persons LTFU relatively low.
| S-EPMC6563456 | biostudies-literature
Project description:BackgroundWe sought to quantify the survival benefits attributable to antiretroviral therapy (ART) in South Africa since 2004.MethodsWe used the Cost-Effectiveness of Preventing AIDS Complications-International model (CEPAC) to simulate 8 cohorts of human immunodeficiency virus (HIV)-infected patients initiating ART each year during 2004-2011. Model inputs included cohort-specific mean CD4(+) T-cell count at ART initiation (112-178 cells/µL), 24-week ART suppressive efficacy (78%), second-line ART availability (2.4% of ART recipients), and cohort-specific 36-month retention rate (55%-71%). CEPAC simulated survival twice for each cohort, once with and once without ART. The sum of the products of per capita survival differences and the total numbers of persons initiating ART for each cohort yielded the total survival benefits.ResultsLifetime per capita survival benefits ranged from 9.3 to 10.2 life-years across the 8 cohorts. Total estimated population lifetime survival benefit for all persons starting ART during 2004-2011 was 21.7 million life-years, of which 2.8 million life-years (12.7%) had been realized by December 2012. By 2030, benefits reached 17.9 million life-years under current policies, 21.7 million life-years with universal second-line ART, 23.3 million life-years with increased linkage to care of eligible untreated patients, and 28.0 million life-years with both linkage to care and universal second-line ART.ConclusionsWe found dramatic past and potential future survival benefits attributable to ART, justifying international support of ART rollout in South Africa.
| S-EPMC3903379 | biostudies-literature
Project description:The MRC/Wits University Agincourt research centre, part of the INDEPTH Network, has documented mortality in a defined population in the rural northeast of South Africa for 20 years (1992-2011) using long-term health and socio-demographic surveillance. Detail on the unfolding, at times unpredicted, mortality pattern has been published. This experience is reviewed here and updated using more recent data.To present a review and summary of mortality patterns across all age-sex groups in the Agincourt sub-district population for the period 1992-2011 as a comprehensive basis for public health action.Vital events in the Agincourt population have been updated in annual surveys undertaken since 1992. All deaths have been rigorously recorded and followed by verbal autopsy interviews. Responses to questions from these interviews have been processed retrospectively using the WHO 2012 verbal autopsy standard and the InterVA-4 model for assigning causes of death in a standardised manner.Between 1992 and 2011, a total of 12,209 deaths were registered over 1,436,195 person-years of follow-up, giving a crude mortality rate of 8.5 per 1,000 person-years. During the 20-year period, the population experienced a major HIV epidemic, which resulted in more than doubling of overall mortality for an extended period. Recent years show signs of declining mortality, but levels remain above the 1992 baseline recorded using the surveillance system.The Agincourt population has experienced a major mortality shock over the past two decades from which it will take time to recover. The basic epidemic patterns are consistent with generalised mortality patterns observed in South Africa as a whole, but the detailed individual surveillance behind these analyses allows finer-grained analyses of specific causes, age-related risks, and trends over time. These demonstrate the complex, somewhat unpredicted course of mortality transition over the years since the dawn of South Africa's democratic era in 1994.
| S-EPMC4220148 | biostudies-literature