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Estimating the impact of antiretroviral treatment on adult mortality trends in South Africa: A mathematical modelling study.

ABSTRACT: BACKGROUND:Substantial reductions in adult mortality have been observed in South Africa since the mid-2000s, but there has been no formal evaluation of how much of this decline is attributable to the scale-up of antiretroviral treatment (ART), as previous models have not been calibrated to vital registration data. We developed a deterministic mathematical model to simulate the mortality trends that would have been expected in the absence of ART, and with earlier introduction of ART. METHODS AND FINDINGS:Model estimates of mortality rates in ART patients were obtained from the International Epidemiology Databases to Evaluate AIDS-Southern Africa (IeDEA-SA) collaboration. The model was calibrated to HIV prevalence data (1997-2013) and mortality data from the South African vital registration system (1997-2014), using a Bayesian approach. In the 1985-2014 period, 2.70 million adult HIV-related deaths occurred in South Africa. Adult HIV deaths peaked at 231,000 per annum in 2006 and declined to 95,000 in 2014, a reduction of 74.7% (95% CI: 73.3%-76.1%) compared to the scenario without ART. However, HIV mortality in 2014 was estimated to be 69% (95% CI: 46%-97%) higher in 2014 (161,000) if the model was calibrated only to HIV prevalence data. In the 2000-2014 period, the South African ART programme is estimated to have reduced the cumulative number of HIV deaths in adults by 1.72 million (95% CI: 1.58 million-1.84 million) and to have saved 6.15 million life years in adults (95% CI: 5.52 million-6.69 million). This compares with a potential saving of 8.80 million (95% CI: 7.90 million-9.59 million) life years that might have been achieved if South Africa had moved swiftly to implement WHO guidelines (2004-2013) and had achieved high levels of ART uptake in HIV-diagnosed individuals from 2004 onwards. The model is limited by its reliance on all-cause mortality data, given the lack of reliable cause-of-death reporting, and also does not allow for changes over time in tuberculosis control programmes and ART effectiveness. CONCLUSIONS:ART has had a dramatic impact on adult mortality in South Africa, but delays in the rollout of ART, especially in the early stages of the ART programme, have contributed to substantial loss of life. This is the first study to our knowledge to calibrate a model of ART impact to population-level recorded death data in Africa; models that are not calibrated to population-level death data may overestimate HIV-related mortality.

SUBMITTER: Johnson LF

PROVIDER: S-EPMC5726614 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Estimating the impact of antiretroviral treatment on adult mortality trends in South Africa: A mathematical modelling study.

Johnson Leigh F LF May Margaret T MT Dorrington Rob E RE Cornell Morna M Boulle Andrew A Egger Matthias M Davies Mary-Ann MA

PLoS medicine 20171212 12

<h4>Background</h4>Substantial reductions in adult mortality have been observed in South Africa since the mid-2000s, but there has been no formal evaluation of how much of this decline is attributable to the scale-up of antiretroviral treatment (ART), as previous models have not been calibrated to vital registration data. We developed a deterministic mathematical model to simulate the mortality trends that would have been expected in the absence of ART, and with earlier introduction of ART.<h4>M ...[more]

PMID: 29232366

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Project description:BACKGROUND:Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis are emerging worldwide. The Green Light Committee initiative supported programmatic management of drug-resistant tuberculosis in 90 countries. We used estimates from the Preserving Effective TB Treatment Study to predict MDR and XDR tuberculosis trends in four countries with a high burden of MDR tuberculosis: India, the Philippines, Russia, and South Africa. METHODS:We calibrated a compartmental model to data from drug resistance surveys and WHO tuberculosis reports to forecast estimates of incident MDR and XDR tuberculosis and the percentage of incident MDR and XDR tuberculosis caused by acquired drug resistance, assuming no fitness cost of resistance from 2000 to 2040 in India, the Philippines, Russia, and South Africa. FINDINGS:The model forecasted the percentage of MDR tuberculosis among incident cases of tuberculosis to increase, reaching 12·4% (95% prediction interval 9·4-16·2) in India, 8·9% (4·5-11·7) in the Philippines, 32·5% (27·0-35·8) in Russia, and 5·7% (3·0-7·6) in South Africa in 2040. It also predicted the percentage of XDR tuberculosis among incident MDR tuberculosis to increase, reaching 8·9% (95% prediction interval 5·1-12·9) in India, 9·0% (4·0-14·7) in the Philippines, 9·0% (4·8-14·2) in Russia, and 8·5% (2·5-14·7) in South Africa in 2040. Acquired drug resistance would cause less than 30% of incident MDR tuberculosis during 2000-40. Acquired drug resistance caused 80% of incident XDR tuberculosis in 2000, but this estimate would decrease to less than 50% by 2040. INTERPRETATION:MDR and XDR tuberculosis were forecast to increase in all four countries despite improvements in acquired drug resistance shown by the Green Light Committee-supported programmatic management of drug-resistant tuberculosis. Additional control efforts beyond improving acquired drug resistance rates are needed to stop the spread of MDR and XDR tuberculosis in countries with a high burden of MDR tuberculosis. FUNDING:US Agency for International Development and US Centers for Disease Control and Prevention, Division of Tuberculosis Elimination.

Project description:BACKGROUND:Measuring and monitoring progress towards Millennium Development Goals (MDG) 4 and 5 required valid and reliable estimates of maternal and child mortality. In South Africa, there are conflicting reports on the estimates of maternal and neonatal mortality, derived from both direct and indirect estimation techniques. This study aimed to systematically review the estimates made of maternal and neonatal mortality in the period from 1990 to 2015 in South Africa and determine trends over this period. METHODS:Nationally-representative studies reporting on maternal and neonatal mortality in South Africa were included for synthesis. Literature search for eligible studies was conducted in five electronic databases: Medline, Africa-Wide Information, Scopus, Web of Science and CINAHL. Searches were restricted to articles written in English and presenting data covering the period between 1990 and 2015. Reference lists of retrieved articles were screened for additional publications, and grey literature was searched for relevant documents for the review. Three independent reviewers were involved in study selection, data extractions and achieving consensus. RESULTS:In total, 969 studies were retrieved and 670 screened for eligibility yielding 25 studies reporting data on maternal mortality and 14 studies on neonatal mortality. Most of the studies had a low risk of bias. Estimates from the institutional reporting differed from the international metrics with wide uncertainty/confidence intervals. Moreover, modelled estimates were widely divergent from estimates obtained through empirical methods. In the last two decades, both maternal and neonatal mortality appear to have increased up to 2009, followed by a decrease, more pronounced in the care of maternal mortality. CONCLUSION:Estimates from both global metrics and institutional reporting, although widely divergent, indicate South Africa has not achieved MDG 4a and 5a goals but made a significant progress in reducing maternal and neonatal mortality. To obtain more accurate estimates, there is a need for applying additional estimation techniques which utilise available multiple data sources to correct for underreporting of these outcomes, perhaps the capture-recapture method. SYSTEMATIC REVIEW REGISTRATION:PROSPERO CRD42016042769.

Project description:BACKGROUND:Globally, illness and life expectancy follow a social gradient that puts people of lower socioeconomic status (SES) at higher risk of dying prematurely. Alcohol consumption has been shown to be a factor contributing to socioeconomic differences in mortality. However, little evidence is available from low- and middle-income countries. The objective of this study was to quantify mortality attributable to alcohol consumption in the adult (15+ years) general population of South Africa in 2015 by SES, age, and sex. METHODS:A comparative risk assessment was performed using individual and aggregate data from South Africa and risk relations reported in the literature. Alcohol-attributable fractions (AAFs) and alcohol-attributable mortality rates were estimated for cause-specific mortality by SES, sex, and age. Monte Carlo simulation techniques were used to calculate 95% uncertainty intervals (UI). RESULTS:Overall, approximately 62,300 (95% UI 27,000-103,000) adults died from alcohol-attributable causes in South Africa in 2015, with 60% of deaths occurring in people in the low and 15% in the high SES groups. Age-standardized, alcohol-attributable mortality rates per 100,000 adults were highest for the low SES group (727 deaths, 95% UI 354-1208 deaths) followed by the middle (377 deaths, 95% UI 165-687 deaths) and high SES groups (163 deaths, 95% UI 71-289 deaths). The socioeconomic differences were highest for mortality from infectious diseases. People of low SES had a lower prevalence of current alcohol use but heavier drinking patterns among current drinkers. Among men, AAFs were elevated at low and middle SES, particularly for the middle and higher age groups (35+). Among women, AAFs differed less across SES groups and, in the youngest age group (15-34), women of high SES had elevated AAFs. CONCLUSIONS:Alcohol use contributed to vast socioeconomic differences in mortality. Where observed, elevated AAFs for people of low and middle SES arose from higher levels of consumption among current drinkers and not from the prevalence of current alcohol use per se. The findings can direct preventive measures and interventions on those at highest risk. Future research is needed to investigate socioeconomic differences in the risk functions relating alcohol use to cause-specific mortality.

Project description:BACKGROUND:Antiretroviral therapy (ART) substantially decreases morbidity and mortality in people living with HIV. In this study, we describe population-level trends in the adult life expectancy and trends in the residual burden of HIV mortality after the roll-out of a public sector ART programme in KwaZulu-Natal, South Africa, one of the populations with the most severe HIV epidemics in the world. METHODS:Data come from the Africa Centre Demographic Information System (ACDIS), an observational community cohort study in the uMkhanyakude district in northern KwaZulu-Natal, South Africa. We used non-parametric survival analysis methods to estimate gains in the population-wide life expectancy at age 15 years since the introduction of ART, and the shortfall of the population-wide adult life expectancy compared with that of the HIV-negative population (ie, the life expectancy deficit). Life expectancy gains and deficits were further disaggregated by age and cause of death with demographic decomposition methods. FINDINGS:Covering the calendar years 2001 through to 2014, we obtained information on 93?903 adults who jointly contribute 535?42 8 person-years of observation to the analyses and 9992 deaths. Since the roll-out of ART in 2004, adult life expectancy increased by 15·2 years for men (95% CI 12·4-17·8) and 17·2 years for women (14·5-20·2). Reductions in pulmonary tuberculosis and HIV-related mortality account for 79·7% of the total life expectancy gains in men (8·4 adult life-years), and 90·7% in women (12·8 adult life-years). For men, 9·5% is the result of a decline in external injuries. By 2014, the life expectancy deficit had decreased to 1·2 years for men (-2·9 to 5·8) and to 5·3 years for women (2·6-7·8). In 2011-14, pulmonary tuberculosis and HIV were responsible for 84·9% of the life expectancy deficit in men and 80·8% in women. INTERPRETATION:The burden of HIV on adult mortality in this population is rapidly shrinking, but remains large for women, despite their better engagement with HIV-care services. Gains in adult life-years lived as well as the present life expectancy deficit are almost exclusively due to differences in mortality attributed to HIV and pulmonary tuberculosis. FUNDING:Wellcome Trust, the Bill & Melinda Gates Foundation, and the National Institutes of Health.

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Estimating the impact of antiretroviral treatment on adult mortality trends in South Africa: A mathematical modelling study.

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Estimating the impact of antiretroviral treatment on adult mortality trends in South Africa: A mathematical modelling study.

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