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      The burden of HIV mortality following the rollout of antiretroviral therapy: evidence from an observational community cohort study in KwaZulu-Natal, South Africa

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          Summary

          Background

          Antiretroviral therapy (ART) substantially decreases morbidity and mortality among people living with HIV. In this study, we describe population-level trends in the adult life expectancy (LE), and trends in the residual burden of HIV mortality following the rollout of a public sector ART programme in one of the populations with the most severe HIV epidemics in the world.

          Methods

          Data come from a demographic and HIV surveillance system in northern KwaZulu-Natal (South Africa), and cover the calendar years 2001 through 2014. We use non-parametric survival analysis methods to estimate gains in the population-wide LE at age 15 since the introduction of ART, and the shortfall of the population-wide adult LE compared to that of the HIV negative population (i.e., the LE deficit). LE gains and deficits are further disaggregated by age and cause of death using demographic decomposition methods.

          Findings

          The dataset contains information on 93,903 adults who jointly contribute 535,428 person-years of observation to the analyses and 9,992 deaths. Since the rollout of ART in 2004, adult LE increased by 15·2 years for men (95%-CI: 12·4-17·8), and 17·2 years for women (95%-CI: 14·5-20·2). Reductions in pulmonary TB and HIV related mortality account for 79·7% of the LE gains among men, and 90·7% among women. For men, 9·5% is the result of a decline in external injuries. By 2014, the LE deficit had contracted to 1·2 years for men (95%-CI: -2·9-5·8) and to 5·3 years for women (95%-CI: 2·6-7·8). Pulmonary TB and HIV are responsible for 84·9% of the LE deficit among men in 2011-'14, and for 80·8% among women.

          Interpretation

          The burden of HIV on adult mortality in this population is rapidly shrinking, but remains sizable for women, despite their better engagement with HIV care services. The recent gains in adult life-years lived as well as the current LE deficit are almost exclusively due to differences in mortality attributed to HIV and pulmonary TB.

          Funding

          Wellcome Trust, the Bill and Melinda Gates Foundation, and the National Institutes of Health.

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          Most cited references 37

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          High coverage of ART associated with decline in risk of HIV acquisition in rural KwaZulu-Natal, South Africa.

          The landmark HIV Prevention Trials Network (HPTN) 052 trial in HIV-discordant couples demonstrated unequivocally that treatment with antiretroviral therapy (ART) substantially lowers the probability of HIV transmission to the HIV-uninfected partner. However, it has been vigorously debated whether substantial population-level reductions in the rate of new HIV infections could be achieved in "real-world" sub-Saharan African settings where stable, cohabiting couples are often not the norm and where considerable operational challenges exist to the successful and sustainable delivery of treatment and care to large numbers of patients. We used data from one of Africa's largest population-based prospective cohort studies (in rural KwaZulu-Natal, South Africa) to follow up a total of 16,667 individuals who were HIV-uninfected at baseline, observing individual HIV seroconversions over the period 2004 to 2011. Holding other key HIV risk factors constant, individual HIV acquisition risk declined significantly with increasing ART coverage in the surrounding local community. For example, an HIV-uninfected individual living in a community with high ART coverage (30 to 40% of all HIV-infected individuals on ART) was 38% less likely to acquire HIV than someone living in a community where ART coverage was low (<10% of all HIV-infected individuals on ART).
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            Increases in adult life expectancy in rural South Africa: valuing the scale-up of HIV treatment.

            The scale-up of antiretroviral therapy (ART) is expected to raise adult life expectancy in populations with high HIV prevalence. Using data from a population cohort of over 101,000 individuals in rural KwaZulu-Natal, South Africa, we measured changes in adult life expectancy for 2000-2011. In 2003, the year before ART became available in the public-sector health system, adult life expectancy was 49.2 years; by 2011, adult life expectancy had increased to 60.5 years--an 11.3-year gain. Based on standard monetary valuation of life, the survival benefits of ART far outweigh the costs of providing treatment in this community. These gains in adult life expectancy signify the social value of ART and have implications for the investment decisions of individuals, governments, and donors.
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              Patient retention in antiretroviral therapy programs up to three years on treatment in sub-Saharan Africa, 2007–2009: systematic review

              Objectives To estimate the proportion of all-cause adult patient attrition from antiretroviral therapy (ART) programs in service delivery settings in sub-Saharan Africa through 36 months on treatment. Methods We identified cohorts within Ovid Medline, ISI Web of Knowledge, Cochrane Database of Systematic Reviews and four conference abstract archives. We summarized retention rates from studies describing observational cohorts from sub-Saharan Africa reporting on adult HIV 1- infected patients initiating first-line three-drug ART. We estimated all-cause attrition rates for 6, 12, 18, 24, or 36 months after ART initiation including patients who died or were lost to follow-up (as defined by the author), but excluding transferred patients. Results We analysed 33 sources describing 39 cohorts and 226 307 patients. Patients were more likely to be female (median 65%) and had a median age at initiation of 37 (range 34–40). Median starting CD4 count was 109 cells/mm3. Loss to follow-up was the most common cause of attrition (59%), followed by death (41%). Median attrition at 12, 24 and 36 months was 22.6% (range 7%–45%), 25% (range 11%–32%) and 29.5% (range 13%–36.1%) respectively. After pooling data in a random-effects meta-analysis, retention declined from 86.1% at 6 months to 80.2% at 12 months, 76.8% at 24 months and 72.3% at 36 months. Adjusting for variable follow-up time in a sensitivity analysis, 24 month retention was 70.0% (range: 66.7%–73.3%), while 36 month retention was 64.6% (range: 57.5%–72.1%). Conclusions Our findings document the difficulties in retaining patients in care for lifelong treatment, and the progress being made in raising overall retention rates.
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                Author and article information

                Journal
                101645355
                43213
                Lancet HIV
                Lancet HIV
                The lancet. HIV
                2405-4704
                2352-3018
                22 March 2017
                10 December 2016
                March 2017
                01 March 2018
                : 4
                : 3
                : e113-e121
                Affiliations
                [1 ]Department of Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom
                [2 ]School of Public Health, University of the Witwatersrand, Johannesburg, South Africa
                [3 ]Instituto Nacional de Cancerología, Mexico City, Mexico
                [4 ]Africa Health Research Institute, Durban, South Africa
                [5 ]Department of Infectious Disease Epidemiology, Imperial College, London, United Kingdom
                [6 ]Department of Global Health, Boston University, Boston, United States
                [7 ]Department of Statistics, University of Washington, Seattle, United States
                [8 ]Department of Sociology, The Ohio State University, Columbus, Ohio
                [9 ]Institute of Public Health, University of Heidelberg, Heidelberg, Germany
                [10 ]Harvard T.H. Chan School of Public Health, Harvard University, Boston, United States
                [11 ]Social Statistics and Demography, University of Southampton, Southampton, United Kingdom
                Author notes
                [* ]Corresponding author: Georges Reniers, Department of Population Health, London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, georges.reniers@ 123456lshtm.ac.uk , Telephone: +44(0)20 7299 4775
                Article
                NIHMS836858
                10.1016/S2352-3018(16)30225-9
                5405557
                27956187

                This manuscript version is made available under the CC BY-NC-ND 4.0 license.

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