Suchergebnisse

Background Despite their burden of a triple epidemic of silicosis, tuberculosis and HIV infection, little is known about the mortality experience of miners from the South African mining industry once they leave employment. Such information is important because of the size and dispersion of this population across a number of countries and the progressive nature of these diseases. Methods This study included 306,297 South African miners who left the industry during 2001–2013. The study aimed to calculate crude and standardised mortality rates, identify secular trends in mortality and model demographic and occupational risk factors for mortality. Results Crude mortality rates peaked in the first year after exit (32.8/1000 person-years), decreasing with each year from exit. Overall mortality was 20% higher than in the general population. Adjusted annual mortality halved over the 12 year period. Mortality predictors were being a black miner [adjusted hazard ratio (aHR) 3.30; 95% confidence interval (CI) 3.15–3.46]; underground work (aHR 1.33; 95% CI 1.28–1.39); and gold aHR 1.15 (95% CI 1.12–1.19) or multiple commodity employment (aHR 1.15; 95% CI 1.11–1.19). Conclusions This is the first long-term mortality assessment in the large ex-miner population from the South African mining industry. Mortality patterns follow that of the national HIV-tuberculosis epidemic and antiretroviral treatment availability. However, ex-miners have further elevated mortality and a very high mortality risk in the year after leaving the workforce. Coordinated action between the mining industry, governments and non-governmental organisations is needed to reduce the impact of this precarious transition.

AbstractIntroductionModel‐based estimates of key HIV indicators depend on past epidemic trends that are derived based on assumptions about HIV disease progression and mortality in the absence of antiretroviral treatment (ART). Population‐based HIV Impact Assessment (PHIA) household surveys conducted between 2015 and 2018 found substantial numbers of respondents living with untreated HIV infection. CD4 cell counts measured in these individuals provide novel information to estimate HIV disease progression and mortality rates off ART.MethodsWe used Bayesian multi‐parameter evidence synthesis to combine data on (1) cross‐sectional CD4 cell counts among untreated adults living with HIV from 10 PHIA surveys, (2) survival after HIV seroconversion in East African seroconverter cohorts, (3) post‐seroconversion CD4 counts and (4) mortality rates by CD4 count predominantly from European, North American and Australian seroconverter cohorts. We used incremental mixture importance sampling to estimate HIV natural history and ART uptake parameters used in the Spectrum software. We validated modelled trends in CD4 count at ART initiation against ART initiator cohorts in sub‐Saharan Africa.ResultsMedian untreated HIV survival decreased with increasing age at seroconversion, from 12.5 years [95% credible interval (CrI): 12.1–12.7] at ages 15–24 to 7.2 years (95% CrI: 7.1–7.7) at ages 45–54. Older age was associated with lower initial CD4 counts, faster CD4 count decline and higher HIV‐related mortality rates. Our estimates suggested a weaker association between ART uptake and HIV‐related mortality rates than previously assumed in Spectrum. Modelled CD4 counts in untreated people living with HIV matched recent household survey data well, though some intercountry variation in frequencies of CD4 counts above 500 cells/mm3 was not explained. Trends in CD4 counts at ART initiation were comparable to data from ART initiator cohorts. An alternate model that stratified progression and mortality rates by sex did not improve model fit appreciably.ConclusionsSynthesis of multiple data sources results in similar overall survival as previous Spectrum parameter assumptions but implies more rapid progression and longer survival in lower CD4 categories. New natural history parameter values improve consistency of model estimates with recent cross‐sectional CD4 data and trends in CD4 counts at ART initiation.

AbstractIntroductionDaily oral pre‐exposure prophylaxis (PrEP) can reduce HIV acquisition. However, prevention effectiveness requires daily adherence prior to and during periods of sexual activity. Little is known about pharmacologic measures of PrEP adherence during pregnancy and postpartum and the factors related to optimal adherence during periods of sexual activity in this population.MethodsBetween August 2019 and October 2021, we enrolled pregnant women without HIV at their first antenatal care visit followed‐up through 12 months postpartum. Eligible women ≥16 years old received HIV prevention counselling and were offered oral PrEP (TDF‐FTC). We quantified tenofovir‐diphosphate (TFV‐DP) in dried blood spots in women who reported taking PrEP in the past 30 days (at quarterly follow‐up visits). We used regression models with generalized estimating equations to evaluate correlates of TFV‐DP (any vs. none, and ≥2 vs. <2 doses/week), adjusting for maternal age and pregnancy status.Results and discussionIn 382 women who started PrEP in pregnancy, returned for follow‐up and reported PrEP use in the past 30 days, the median age was 27 years (interquartile range [IQR] = 23–32), and the median time on PrEP was 168 days (IQR = 84–252 days). Half of the samples had quantifiable TFV‐DP at any time point (52%), declining from 67% of pregnant women 3 months post‐initiation to 31% of postpartum women by 12 months. Overall, 72% had concentrations corresponding to <2 doses/week; 25% ≥2 doses/week; 3% 7 doses/week. Concentrations were lower in postpartum versus pregnancy (age‐adjusted odds ratio [aOR] = 0.44; 95% confidence interval [CI] = 0.35–0.54). The correlation of self‐reported adherence and TFV‐DP ranged from –0.07 in pregnancy to 0.25 in postpartum women. Variables associated with having quantifiable TFV‐DP included partner living with HIV/unknown serostatus (aOR = 1.50; 95% CI = 1.01–2.22), and reported frequency of sexual activity in the past month (aOR sex >5/month vs. no sex or <5 times/month = 2.11; 95% CI = 1.58–2.82) adjusting for age and pregnancy versus postpartum status. TFV‐DP concentrations declined over follow‐up time (aOR for 6 vs. 3 months = 0.49; 95% CI = 0.36–0.67).ConclusionsObjectively measured adherence to PrEP was low overall and did not correlate with self‐reported use. There is an urgent need for objective adherence measures to support clinical decision‐making as well as adherence support interventions as part of PrEP services for pregnant and postpartum women at risk of HIV.

AbstractIntroduction: South Africa has the largest number of individuals living with HIV and the largest antiretroviral therapy (ART) programme worldwide. In September 2016, ART eligibility was extended to all 7.1 million HIV‐positive South Africans. To ensure that further expansion of services does not compromise quality of care, long‐term outcomes must be monitored. Few studies have reported long‐term mortality in resource‐constrained settings, where mortality ascertainment is challenging. Combining site records with data linked to the national vital registration system, sites in the International Epidemiology Databases to Evaluate AIDS Southern Africa collaboration can identify >95% of deaths in patients with civil identification numbers (IDs). This study used linked data to explore long‐term mortality and viral suppression among adults starting ART in South Africa.Methods: The study was a cohort analysis of routine data on adults with IDs starting ART 2004–2015 in five large ART cohorts. Mortality was estimated overall and by gender using the Kaplan‐Meier estimator and Cox's proportional hazards regression. Standardized mortality ratios (SMRs) were calculated by dividing observed numbers of deaths by numbers expected if patients had been HIV‐negative. Viral suppression in patients with viral loads (VLs) in their last year of follow‐up was the secondary outcome.Results: Among 72,812 adults followed for 350,376 person years (pyrs), the crude mortality rate was 3.08 (95% CI 3.02–3.14)/100 pyrs. Patients were predominantly female (67%) and the percentage of men initiating ART did not increase. Cumulative mortality 12 years after ART initiation was 23.9% (33.4% male and 19.4% female). Mortality peaked in patients enrolling in 2007–2009 and was higher in men than women at all durations. Observed mortality rates were higher than HIV‐negative mortality, decreasing with duration. By 48 months, observed mortality was close to that in the HIV‐negative population, and SMRs were similar for all baseline CD4 strata. Three‐quarters of patients had VLs in their last year, and 86% of these were virally suppressed.Conclusions: The South African ART programme has shown a remarkable ability to initiate and manage patients successfully over 12 years, despite rapid expansion. With further scale‐up, testing and initiating men on ART must be a national priority.

AbstractIntroductionIn 2016, South Africa (SA) initiated a national programme to scale‐up pre‐exposure prophylaxis (PrEP) among female sex workers (FSWs), with ∼20,000 PrEP initiations among FSWs (∼14% of FSW) by 2020. We evaluated the impact and cost‐effectiveness of this programme, including future scale‐up scenarios and the potential detrimental impact of the COVID‐19 pandemic.MethodsA compartmental HIV transmission model for SA was adapted to include PrEP. Using estimates on self‐reported PrEP adherence from a national study of FSW (67.7%) and the Treatment and Prevention for FSWs (TAPS) PrEP demonstration study in SA (80.8%), we down‐adjusted TAPS estimates for the proportion of FSWs with detectable drug levels (adjusted range: 38.0–70.4%). The model stratified FSW by low (undetectable drug; 0% efficacy) and high adherence (detectable drug; 79.9%; 95% CI: 67.2–87.6% efficacy). FSWs can transition between adherence levels, with lower loss‐to‐follow‐up among highly adherent FSWs (aHR: 0.58; 95% CI: 0.40–0.85; TAPS data). The model was calibrated to monthly data on the national scale‐up of PrEP among FSWs over 2016–2020, including reductions in PrEP initiations during 2020. The model projected the impact of the current programme (2016–2020) and the future impact (2021–2040) at current coverage or if initiation and/or retention are doubled. Using published cost data, we assessed the cost‐effectiveness (healthcare provider perspective; 3% discount rate; time horizon 2016–2040) of the current PrEP provision.ResultsCalibrated to national data, model projections suggest that 2.1% of HIV‐negative FSWs were currently on PrEP in 2020, with PrEP preventing 0.45% (95% credibility interval, 0.35–0.57%) of HIV infections among FSWs over 2016–2020 or 605 (444–840) infections overall. Reductions in PrEP initiations in 2020 possibly reduced infections averted by 18.57% (13.99–23.29). PrEP is cost‐saving, with $1.42 (1.03–1.99) of ART costs saved per dollar spent on PrEP. Going forward, existing coverage of PrEP will avert 5,635 (3,572–9,036) infections by 2040. However, if PrEP initiation and retention doubles, then PrEP coverage increases to 9.9% (8.7–11.6%) and impact increases 4.3 times with 24,114 (15,308–38,107) infections averted by 2040.ConclusionsOur findings advocate for the expansion of PrEP to FSWs throughout SA to maximize its impact. This should include strategies to optimize retention and should target women in contact with FSW services.

IntroductionThere is uncertainty regarding the completeness of death recording by civil registration and by health centres in South Africa. This paper aims to compare death recording by the two systems, in cohorts of South African patients receiving antiretroviral treatment (ART).MethodsCompleteness of death recording was estimated using a capture–recapture approach. Six ART programmes linked their patient record systems to the vital registration system using civil identity document (ID) numbers and provided data comparing the outcomes recorded in patient files and in the vital registration. Patients were excluded if they had missing/invalid IDs or had transferred to other ART programmes.ResultsAfter exclusions, 91,548 patient records were included. Of deaths recorded in patients files after 2003, 94.0% (95% CI: 93.3–94.6%) were recorded by civil registration, with completeness being significantly higher in urban areas, older adults and females. Of deaths recorded by civil registration after 2003, only 35.0% (95% CI: 34.2–35.8%) were recorded in patient files, with this proportion dropping from 60% in 2004–2005 to 30% in 2010 and subsequent years. Recording of deaths in patient files was significantly higher in children and in locations within 50 km of the health centre. When the information from the two systems was combined, an estimated 96.2% of all deaths were recorded (93.5% in children and 96.2% in adults).ConclusionsSouth Africa's civil registration system has achieved a high level of completeness in the recording of mortality. However, the fraction of deaths recorded by health centres is low and information from patient records is insufficient by itself to evaluate levels and predictors of ART patient mortality. Previously documented improvements in ART mortality over time may be biased if based only on data from patient records.

AbstractIntroductionTo improve the diagnosis and survival of children living with HIV (CLWH), the World Health Organization recommends testing approaches beyond traditional infant HIV testing programmes. Information about undiagnosed HIV prevalence among children of varying ages in the general population is needed to guide innovative national/subnational case‐finding and testing approaches.MethodsWe used the Cost‐Effectiveness of Preventing AIDS Complications (CEPAC)‐Pediatric model to estimate the prevalence of undiagnosed HIV in 2‐, 5‐ and 10‐year‐old children in South Africa, Côte d'Ivoire and Zimbabwe in 2018. We simulated cohorts of children born in 2008 (10‐year‐olds), 2013 (5‐year‐olds) and 2016 (2‐year‐olds). Country‐/year‐specific inputs for pregnant/breastfeeding women included: HIV prevalence (4.2–32.3%), HIV incidence (0.03–0.24%/month), knowledge of HIV status (27–89%) and antiretroviral drug coverage (36–95%). Paediatric inputs included early infant testing coverage (6–95%) and breastfeeding duration (0–20 months). We projected the proportion of surviving CLWH in whom HIV remained undiagnosed and the undiagnosed HIV prevalence among surviving children of each age in the general population. For children born in 2016, we projected survival and diagnosis of all CLWH through 2026. We conducted sensitivity analyses on model parameters.ResultsIn 2018, the projected proportion of surviving CLWH whose HIV remained undiagnosed in South Africa/Côte d'Ivoire/Zimbabwe was 44.2%/55.8%/52.9% among 2‐year‐old CLWH; 29.0%/37.8%/33.2% among 5‐year‐old CLWH; and 18.3%/25.4%/23.1% among 10‐year‐old CLWH. Projected general population undiagnosed HIV prevalence in South Africa/Côte d'Ivoire/Zimbabwe was 0.44%/0.32%/0.68% among 2‐year‐olds; 0.25%/0.17%/0.41% among 5‐year‐olds; and 0.24%/0.14%/0.38% among 10‐year‐olds. Among all CLWH born in 2016, 50–54% were projected to die without HIV diagnosis (and subsequently without treatment) within 10 years after birth; 80–85% of these deaths occurred in the first 2 years.ConclusionsProjected population‐level undiagnosed HIV prevalence is low and sharply decreases after age 2, with more CLWH dying than being diagnosed. Despite low undiagnosed prevalence in the general population of older children, we project that a large proportion of CLWH remain undiagnosed, suggesting that innovative strategies targeting untested children of all ages outside of health facility settings should be prioritized. Programmes could consider routine testing of the general population of children below 2 in all settings and children of all ages in high‐prevalence settings.

AbstractIntroductionThe third of the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90‐90‐90 targets is to achieve a 90% rate of viral suppression (HIV viral load <1000 HIV‐1 RNA copies/ml) in patients on antiretroviral treatment (ART) by 2020. However, some countries use different thresholds when reporting viral suppression, and there is thus a need for an adjustment to standardize estimates to the <1000 threshold. We aim to propose such an adjustment, to support consistent monitoring of progress towards the "third 90" target.MethodsWe considered three possible distributions for viral loads in ART patients: Weibull, Pareto and reverse Weibull (imposing an upper limit but no lower limit on the log scale). The models were fitted to data on viral load distributions in ART patients in the International epidemiology Databases to Evaluate AIDS (IeDEA) collaboration (representing seven global regions) and the ART Cohort Collaboration (representing Europe), using separate random effects models for adults and children. The models were validated using data from the World Health Organization (WHO) HIV drug resistance report and the Brazilian national ART programme.ResultsModels were calibrated using 921,157 adult and 37,431 paediatric viral load measurements, over 2010–2019. The Pareto and reverse Weibull models provided the best fits to the data, but for all models, the "shape" parameters for the viral load distributions differed significantly between regions. The Weibull model performed best in the validation against the WHO drug resistance survey data, while the Pareto model produced uncertainty ranges that were too narrow, relative to the validation data. Based on these analyses, we recommend using the reverse Weibull model. For example, if a country reports an 80% rate of viral suppression at <200 copies/ml, this model estimates the proportion virally suppressed at <1000 copies/ml is 88.3% (0.800.56), with uncertainty range 85.5–90.6% (0.800.70–0.800.44).ConclusionsEstimates of viral suppression can change substantially depending on the threshold used in defining viral suppression. It is, therefore, important that viral suppression rates are standardized to the same threshold for the purpose of assessing progress towards UNAIDS targets. We have proposed a simple adjustment that allows this, and this has been incorporated into UNAIDS modelling software.

AbstractIntroductionThe Joint United Nations Programme on HIV/AIDS (UNAIDS) projections of paediatric HIV prevalence and deaths rely on the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium for mortality estimates among children living with HIV (CHIV) receiving antiretroviral therapy (ART). Previous estimates, based on data through 2014, may no longer be accurate due to expanded paediatric HIV care and treatment eligibility, and the possibility of unreported deaths in CHIV considered lost to follow‐up (LTFU). We therefore estimated all‐cause mortality and its trends in CHIV (<15 years old) on ART using extended and new IeDEA data.MethodsWe analysed (i) IeDEA observational data from CHIV in routine care globally, and (ii) novel data from an IeDEA tracing study that determined outcomes in a sample of CHIV after being LTFU in southern Africa. We included 45,711 CHIV on ART during 2004 to 2017 at 72 programmes in Africa, Asia‐Pacific and Latin America. We used mixed effects Poisson regression to estimate mortality by age, sex, CD4 at ART start, time on ART, region and calendar year. For Africa, in an adjusted analysis that accounts for unreported deaths among those LTFU, we first modified the routine data by simulating mortality outcomes within six months after LTFU, based on a Gompertz survival model fitted to the tracing data (n = 221).ResultsObserved mortality rates were 1.8 (95% CI: 1.7 to 1.9) and 9.4 (6.3 to 13.4) deaths per 100 person‐years in the routine and tracing data, respectively. We found strong evidence of higher mortality at shorter ART durations, lower CD4 values, and in infancy. Averaging over covariate patterns, the adjusted mortality rate was 54% higher than the unadjusted rate. In unadjusted analyses, mortality reduced by an average 60% and 73% from 2005 to 2017, within and outside of Africa, respectively. In the adjusted analysis for Africa, this temporal reduction was 42%.ConclusionsMortality rates among CHIV have decreased substantially over time. However, when accounting for worse outcomes among those LTFU, mortality estimates increased and temporal improvements were slightly reduced, suggesting caution in interpreting analyses based only on programme data. The improved and updated IeDEA estimates on mortality among CHIV on ART support UNAIDS efforts to accurately model global HIV statistics.