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This paper investigates the effect of under-five mortality, child support grant (CSG) coverage and the rollout of antiretroviral therapy (ART) on fertility in South Africa. The study employs the quality-quantity trade-off framework to analyse the direct and indirect factors affecting fertility using the two stage least squares fixed effects instrumental variable approach. The analysis uses balanced panel data covering nine provinces from 2001-2016. This period was characterised by significant increases in the child support grant coverage and ART coverage. Furthermore, this period was characterised by a significant decline in the under-five mortality rate. We find no evidence to support the hypothesis that increases in the CSG coverage are associated with an increase in fertility. This finding aligns with previous literature suggesting that there are no perverse incentives for childbearing associated with the child support grant. On the other hand, results indicate that an increase in ART coverage is associated with an increase in fertility. Results also show that a decrease in under-five mortality is associated with a decline in fertility over the sample period. HIV prevalence, education, real GDP per capita, marriage prevalence and contraceptive prevalence are also important determinants of fertility in South Africa. Although the scale up of ART has improved health outcomes, it also appears to have increased fertility in HIV-positive women. The ART programme should therefore be linked with further family planning initiatives to minimise unintended pregnancies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Bidzha et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Recent studies have shown HIV incidence declines at a population level in several African countries. However, these studies have not directly quantified the extent to which incidence declines are attributable to different HIV programs., Methods: We calibrated a mathematical model of the South African HIV epidemic to age- and sex-specific data from antenatal surveys, household surveys, and death registration, using a Bayesian approach. The model was also parameterized using data on self-reported condom use, voluntary medical male circumcision (VMMC), HIV testing, and antiretroviral treatment (ART). Model estimates of HIV incidence were compared against the incidence rates that would have been expected had each program not been implemented., Results: The model estimated incidence in 15-49 year olds of 0.84% (95% CI: 0.75% to 0.96%) at the start of 2019. This represents a 62% reduction (95% CI: 55% to 66%) relative to 2000, a 47% reduction (95% CI: 42% to 51%) relative to 2010, and a 73% reduction (95% CI: 68% to 77%) relative to the incidence that would have been expected in 2019 in the absence of any interventions. The reduction in incidence in 2019 because of interventions was greatest for ART and condom promotion, with VMMC and behavior change after HIV testing having relatively modest impacts. HIV program impacts differed significantly by age and sex, with condoms and VMMC having greatest impact in youth, and overall incidence reductions being greater in men than in women., Conclusions: HIV incidence in South Africa has declined substantially since 2000, with ART and condom promotion contributing most significantly to this decline., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Globally, large proportions of HIV-positive populations live in cities. The Fast-Track cities project aims to advance progress toward elimination of HIV as a public health threat by accelerating the response in cities across the world. This study applies a well-established HIV transmission model to provide key HIV estimates for the five largest metropolitan districts in South Africa (SA): Cape Town, Ekurhuleni, eThekwini, Johannesburg and Tshwane. We calibrate the model to metro-specific data sources and estimate progress toward the 90-90-90 targets set by UNAIDS (90% of people living with HIV (PLHIV) diagnosed, 90% of those diagnosed on antiretroviral therapy (ART) and viral suppression in 90% of those on ART). We use the model to predict progress towards similarly defined 95-95-95 targets in 2030. In SA, 90.5% of PLHIV were diagnosed in 2018, with metro estimates ranging from 86% in Johannesburg to 92% in eThekwini. However, only 68.4% of HIV-diagnosed individuals nationally were on ART in 2018, with the proportion ranging from 56% in Tshwane to 73% in eThekwini. Fractions of ART users who were virally suppressed ranged from 77% in Ekurhuleni to 91% in eThekwini, compared to 86% in the whole country. All five metros are making good progress to reach diagnosis targets and all (with the exception of Ekurhuleni) are expected to reach viral suppression targets in 2020. However, the metros and South Africa face severe challenges in reaching the 90% ART treatment target.

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.

Background: The goal of virtual elimination of horizontal and mother-to-child HIV transmission in South Africa (SA) has been proposed, but there have been few systematic investigations of which interventions are likely to be most critical to reducing HIV incidence., Objective: This study aims to evaluate SA's potential to achieve virtual elimination targets and to identify which interventions will be most critical to achieving HIV incidence reductions., Design: A mathematical model was developed to simulate the population-level impact of different HIV interventions in SA. Probability distributions were specified to represent uncertainty around 32 epidemiological parameters that could be influenced by interventions, and correlation coefficients (r) were calculated to assess the sensitivity of the adult HIV incidence rates and mother-to-child transmission rates (2015-2035) to each epidemiological parameter., Results: HIV incidence in SA adults (ages 15-49) is expected to decline from 1.4% in 2011-2012 to 0.29% by 2035 (95% CI: 0.10-0.62%). The parameters most strongly correlated with future adult HIV incidence are the rate of viral suppression after initiating antiretroviral treatment (ART) (r=-0.56), the level of condom use in non-marital relationships (r=-0.40), the phase-in of intensified risk-reduction counselling for HIV-positive adults (r=0.29), the uptake of medical male circumcision (r=-0.24) and the phase-in of universal ART eligibility (r=0.22). The paediatric HIV parameters most strongly associated with mother-to-child transmission rates are the relative risk of transmission through breastfeeding when the mother is receiving ART (r=0.70) and the rate of ART initiation during pregnancy (r=-0.16)., Conclusions: The virtual elimination target of a 0.1% incidence rate in adults will be difficult to achieve. Interventions that address the infectiousness of patients after ART initiation will be particularly critical to achieving long-term HIV incidence declines in South Africa.

Introduction: There 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)., Methods: Completeness 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., Results: After 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)., Conclusions: South 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.

Background: Mathematical models are widely used to simulate the effects of interventions to control HIV and to project future epidemiological trends and resource needs. We aimed to validate past model projections against data from a large household survey done in South Africa in 2012., Methods: We compared ten model projections of HIV prevalence, HIV incidence, and antiretroviral therapy (ART) coverage for South Africa with estimates from national household survey data from 2012. Model projections for 2012 were made before the publication of the 2012 household survey. We compared adult (age 15-49 years) HIV prevalence in 2012, the change in prevalence between 2008 and 2012, and prevalence, incidence, and ART coverage by sex and by age groups between model projections and the 2012 household survey., Findings: All models projected lower prevalence estimates for 2012 than the survey estimate (18·8%), with eight models' central projections being below the survey 95% CI (17·5-20·3). Eight models projected that HIV prevalence would remain unchanged (n=5) or decline (n=3) between 2008 and 2012, whereas prevalence estimates from the household surveys increased from 16·9% in 2008 to 18·8% in 2012 (difference 1·9, 95% CI -0·1 to 3·9). Model projections accurately predicted the 1·6 percentage point prevalence decline (95% CI -0·3 to 3·5) in young adults aged 15-24 years, and the 2·2 percentage point (0·5 to 3·9) increase in those aged 50 years and older. Models accurately represented the number of adults on ART in 2012; six of ten models were within the survey 95% CI of 1·54-2·12 million. However, the differential ART coverage between women and men was not fully captured; all model projections of the sex ratio of women to men on ART were lower than the survey estimate of 2·22 (95% CI 1·73-2·71)., Interpretation: Projections for overall declines in HIV epidemics during the ART era might have been optimistic. Future treatment and HIV prevention needs might be greater than previously forecasted. Additional data about service provision for HIV care could help inform more accurate projections., Funding: Bill & Melinda Gates Foundation., (Copyright © 2015 Eaton et al. Open Access article distributed under the terms of CC BY-NC-ND. Published by Elsevier Ltd.. All rights reserved.)

Objective: To analyse trends in under-five mortality rate in South Africa (1990-2011), particularly the contribution of AIDS deaths., Methods: Three nationally used models for estimating AIDS deaths in children were systematically reviewed. The model outputs were compared with under-five mortality rate estimates for South Africa from two global estimation models. All estimates were compared with available empirical data., Results: Differences between the models resulted in varying point estimates for under-five mortality but the trends were similar, with mortality increasing to a peak around 2005. The three models showing the contribution of AIDS suggest a maximum of 37-39% of child deaths were due to AIDS in 2004-2005 which has since declined. Although the rate of progress from 1990 is not the 4.4% needed to meet Millennium Development Goal 4 for child survival, South Africa's average annual rate of under-five mortality decline between 2006 and 2011 was between 6.3 and 10.2%., Conclusion: In 2005, South Africa was one of only four countries globally with an under-five mortality rate higher than the 1990 Millennium Development Goal baseline. Over the past 5 years, the country has achieved a rate of child mortality reduction exceeded by only three other countries. This rapid turnaround is likely due to scale-up of prevention of mother-to-child transmission of HIV, and to a lesser degree, the expanded roll-out of antiretroviral therapy. Emphasis on these programmes must continue, but failure to address other aspects of care including integrated high-quality maternal and neonatal care means that the decline in child mortality could stall.

Background: Few estimates exist of the life expectancy of HIV-positive adults receiving antiretroviral treatment (ART) in low- and middle-income countries. We aimed to estimate the life expectancy of patients starting ART in South Africa and compare it with that of HIV-negative adults., Methods and Findings: Data were collected from six South African ART cohorts. Analysis was restricted to 37,740 HIV-positive adults starting ART for the first time. Estimates of mortality were obtained by linking patient records to the national population register. Relative survival models were used to estimate the excess mortality attributable to HIV by age, for different baseline CD4 categories and different durations. Non-HIV mortality was estimated using a South African demographic model. The average life expectancy of men starting ART varied between 27.6 y (95% CI: 25.2-30.2) at age 20 y and 10.1 y (95% CI: 9.3-10.8) at age 60 y, while estimates for women at the same ages were substantially higher, at 36.8 y (95% CI: 34.0-39.7) and 14.4 y (95% CI: 13.3-15.3), respectively. The life expectancy of a 20-y-old woman was 43.1 y (95% CI: 40.1-46.0) if her baseline CD4 count was ≥ 200 cells/µl, compared to 29.5 y (95% CI: 26.2-33.0) if her baseline CD4 count was <50 cells/µl. Life expectancies of patients with baseline CD4 counts ≥ 200 cells/µl were between 70% and 86% of those in HIV-negative adults of the same age and sex, and life expectancies were increased by 15%-20% in patients who had survived 2 y after starting ART. However, the analysis was limited by a lack of mortality data at longer durations., Conclusions: South African HIV-positive adults can have a near-normal life expectancy, provided that they start ART before their CD4 count drops below 200 cells/µl. These findings demonstrate that the near-normal life expectancies of HIV-positive individuals receiving ART in high-income countries can apply to low- and middle-income countries as well. Please see later in the article for the Editors' Summary.

Background: Guidelines for treatment of pediatric HIV have recently changed to recommend that all infants who are identified as HIV-infected should start antiretroviral treatment (ART) immediately, regardless of their immunologic or clinical status. This study aims to assess the likely impact of this change in guideline in South Africa., Methods: A mathematical model was developed to simulate mother-to-child transmission of HIV, disease progression, and death of HIV-infected children <15 years of age. The model is calibrated to South African data sources, including prevention of mother-to-child transmission program coverage data, pre-ART survival data, ART program statistics, and pediatric HIV prevalence studies., Results: Relative to what would be expected in the absence of early ART initiation, the number of infant AIDS deaths over the 2010-2025 period is expected to drop by 23.6% (95% confidence interval [CI]: 22.5-24.5%) at current levels of polymerase chain reaction (PCR) diagnosis, and by 34.2% (95% CI: 32.7-35.6%) if PCR diagnosis increases to 80% of perinatally infected infants at 2 months. However, the pediatric HIV disease burden has shifted toward older children in recent years. The effect of early ART on total pediatric AIDS mortality during the 2010-2025 period is therefore modest: a 9.8% reduction (95% CI: 7.9-12.6%) at current levels of PCR diagnosis, and a 14.2% reduction (95% CI: 11.4-18.2%) if PCR coverage increases to 80% of perinatally infected infants., Conclusion: The changes in ART guidelines for infants will have a significant impact on pediatric AIDS mortality at young ages, but further efforts are required to reduce the substantial growing AIDS mortality in older children.

Background: The prevention of mother-to-child transmission (PMTCT) of HIV has been focused mainly on women who are HIV positive at their first antenatal visit, but there is uncertainty regarding the contribution to overall transmission from mothers who seroconvert after their first antenatal visit and before weaning., Method: A mathematical model was developed to simulate changes in mother-to-child transmission of HIV over time, in South Africa. The model allows for changes in infant feeding practices as infants age, temporal changes in the provision of antiretroviral prophylaxis and counseling on infant feeding, as well as temporal changes in maternal HIV prevalence and incidence., Results: The proportion of mother-to-child transmission (MTCT) from mothers who seroconverted after their first antenatal visit was 26% [95% confidence interval (CI): 22% to 30%] in 2008, or 15,000 of 57,000 infections. It is estimated that by 2014, total MTCT will reduce to 39,000 per annum, and transmission from mothers seroconverting after their first antenatal visit will reduce to 13,000 per annum, accounting for 34% (95% CI: 29% to 39%) of MTCT. If maternal HIV incidence during late pregnancy and breastfeeding were reduced by 50% after 2010, and HIV screening were repeated in late pregnancy and at 6-week immunization visits after 2010, the average annual number of MTCT cases over the 2010-2015 period would reduce by 28% (95% CI: 25% to 31%), from 39,000 to 28,000 per annum., Conclusion: Maternal seroconversion during late pregnancy and breastfeeding contributes significantly to the pediatric HIV burden and needs greater attention in the planning of prevention of MTCT programs.

Objectives: To assess the extent to which sexually transmitted infections (STIs) have contributed to the spread of HIV in South Africa and to estimate the extent to which improvements in STI treatment have reduced HIV incidence., Methods: A mathematical model was used to simulate interactions between HIV and six other STIs (genital herpes, syphilis, chancroid, gonorrhoea, chlamydial infection and trichomoniasis) as well as bacterial vaginosis and vaginal candidiasis. The effects of STIs on HIV transmission probabilities were assumed to be consistent with meta-analytic reviews of observational studies, and the model was fitted to South African HIV prevalence data., Results: The proportion of new HIV infections in adults that were attributable to curable STIs reduced from 39% (uncertainty range: 24-50%) in 1990 to 14% (8-18%) in 2010, while the proportion of new infections attributable to genital herpes increased. Syndromic management programmes are estimated to have reduced adult HIV incidence by 6.6% (3.3-10.3%) between 1994 and 2004, by which time syndromic management coverage was 52%. Had syndromic management been introduced in 1986, with immediate achievement of 100% coverage and a doubling of the rate of health seeking, HIV incidence would have reduced by 64% (36-82%) over the next decade, but had the same intervention been delayed until 2004, HIV incidence would have reduced by only 5.5% (2.8-9.0%)., Conclusions: Sexually transmitted infections have contributed significantly to the spread of HIV in South Africa, but STI control efforts have had limited impact on HIV incidence because of their late introduction and suboptimal coverage., (© 2011 Blackwell Publishing Ltd.)

Objectives: To assess the effect of educational attainment and other factors on the risk of HIV in pregnant South African women., Design: Repeated cross-sectional surveys., Methods: Pregnant women attending public antenatal clinics were tested for HIV annually between 2000 and 2005, and provided demographic information. Logistic regression models were applied separately to the data collected in each year, to identify factors associated with HIV infection. Data from all years were combined in a logistic regression model that tested for trends in HIV prevalence., Results: Amongst women aged 15-24 years, HIV risk in those who had completed secondary education was significantly lower than in those who had only primary education, in all years except 2000. HIV risk increased by 8% per annum (odds ratio 1.08, 95% confidence interval 1.04-1.12) in young women with no secondary education but did not increase in young women with secondary education. In women aged 25-49 years, HIV risk increased over the 2000-2005 period, at all levels of educational attainment, and did not differ between women with completed secondary education and women with only primary education., Conclusion: Together with other evidence, this study suggests that higher educational attainment did not protect against HIV in the early stages of the South African HIV/AIDS epidemic. In recent years, the risk of HIV infection in young South African women with completed secondary education has reduced significantly relative to that in young women with primary education, suggesting that HIV prevention strategies may have been more effective in more educated women.

BackgroundThe fifth Millennium Development Goal (MDG 5) established the goal of a 75% reduction in the maternal mortality ratio (MMR; number of maternal deaths per 100,000 livebirths) between 1990 and 2015. We aimed to measure levels and track trends in maternal mortality, the key causes contributing to maternal death, and timing of maternal death with respect to delivery.MethodsWe used robust statistical methods including the Cause of Death Ensemble model (CODEm) to analyse a database of data for 7065 site-years and estimate the number of maternal deaths from all causes in 188 countries between 1990 and 2013. We estimated the number of pregnancy-related deaths caused by HIV on the basis of a systematic review of the relative risk of dying during pregnancy for HIV-positive women compared with HIV-negative women. We also estimated the fraction of these deaths aggravated by pregnancy on the basis of a systematic review. To estimate the numbers of maternal deaths due to nine different causes, we identified 61 sources from a systematic review and 943 site-years of vital registration data. We also did a systematic review of reports about the timing of maternal death, identifying 142 sources to use in our analysis. We developed estimates for each country for 1990-2013 using Bayesian meta-regression. We estimated 95% uncertainty intervals (UIs) for all values.Findings292,982 (95% UI 261,017-327,792) maternal deaths occurred in 2013, compared with 376,034 (343,483-407,574) in 1990. The global annual rate of change in the MMR was -0·3% (-1·1 to 0·6) from 1990 to 2003, and -2·7% (-3·9 to -1·5) from 2003 to 2013, with evidence of continued acceleration. MMRs reduced consistently in south, east, and southeast Asia between 1990 and 2013, but maternal deaths increased in much of sub-Saharan Africa during the 1990s. 2070 (1290-2866) maternal deaths were related to HIV in 2013, 0·4% (0·2-0·6) of the global total. MMR was highest in the oldest age groups in both 1990 and 2013. In 2013, most deaths occurred intrapartum or postpartum. Causes varied by region and between 1990 and 2013. We recorded substantial variation in the MMR by country in 2013, from 956·8 (685·1-1262·8) in South Sudan to 2·4 (1·6-3·6) in Iceland.InterpretationGlobal rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015. Accelerated reductions since the Millennium Declaration in 2000 coincide with increased development assistance for maternal, newborn, and child health. Setting of targets and associated interventions for after 2015 will need careful consideration of regions that are making slow progress, such as west and central Africa.FundingBill & Melinda Gates Foundation.

HIV/AIDS statistics have been the source of much controversy in South Africa, but often the extent of uncertainty around these estimates is ignored. There is need for an assessment of the range of uncertainty around often-quoted HIV/AIDS statistics. This analysis determines ranges of uncertainty around the inputs and outputs of the ASSA2002 AIDS and Demographic model of the South African HIV/AIDS epidemic, using a generalized likelihood uncertainty estimation approach. A sample of 500 parameter combinations was drawn by weighting randomly generated parameter combinations by likelihood functions defined on the basis of four South African HIV/AIDS data sets. The estimated number of HIV infections in mid-2005 was 5.1 million (95% prediction interval: 4.2-6.0 million), equivalent to an HIV prevalence rate of 11.1% (9.1-13.1%). Between mid-2004 and mid-2005, the estimated number of new HIV infections was 490 000 (370 000-590 000) and the estimated number of AIDS deaths was 320 000 (270 000-380 000). The posterior mean HIV survival time was estimated to be 11.5 years (95% credibility interval: 10.0-12.9 years), longer than estimated for elsewhere in the developing world. This analysis confirms that South Africa is experiencing a severe HIV/AIDS epidemic, and suggests that HIV/AIDS epidemiology in the country probably differs from that elsewhere in Africa. [ABSTRACT FROM AUTHOR]