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Abstract Despite expanded antiretroviral therapy (ART) in South Africa, HIV-1 transmission persists. Integrase strand transfer inhibitors (INSTI) and long-acting injectables offer potential for superior viral suppression, but pre-existing drug resistance could threaten their effectiveness. In a community-based study in rural KwaZulu-Natal, prior to widespread INSTI usage, we enroled 18,025 individuals to characterise HIV-1 drug resistance and transmission networks to inform public health strategies. HIV testing and reflex viral load quantification were performed, with deep sequencing (20% variant threshold) used to detect resistance mutations. Phylogenetic and geospatial analyses characterised transmission clusters. One-third of participants were HIV-positive, with 21.7% having detectable viral loads; 62.1% of those with detectable viral loads were ART-naïve. Resistance to older reverse transcriptase (RT)-targeting drugs was found, but INSTI resistance remained low (

Background: We sought to improve the current understanding of how climate change impacts women’s reproductive health in sub-Saharan Africa. Objectives: We investigated the relationship between maternal heat exposure and miscarriage (pregnancy ending before 20 weeks gestation) in a South African setting. Design: Population-based cohort study. Methods: Our study involved data for pregnancies collected via a health and demographic surveillance system in rural KwaZulu-Natal, South Africa between 2012 and 2016. Data from the South African Weather Service were used to compute maternal exposure to heat during the following time windows for each pregnancy: during the month preceding conception (T1) and during the week preceding the study outcome (either a miscarriage or no miscarriage, T2). Heat exposure was operationalized as a continuous variable and defined as the number of days that a mother was exposed to a mean daily temperature of > 26.6°C (A “hot day,” equivalent to a mean daily temperature of > 80°F) during T1 or T2. Binary logistic regression was used to investigate the relationship between maternal heat exposure and miscarriage. Results: A total of 105/3477 pregnancies included in our analysis ended in miscarriage (3.0%). Each additional hot day during T1 was associated with a 26% higher odds of miscarriage (odds ratio: 1.26; 95% confidence interval: 1.15–1.38). No significant associations were observed between maternal heat exposure during T2 and the odds of miscarriage (odds ratio: 0.94, 95% confidence interval: 0.73–1.20). The relationship between maternal heat exposure during T1 and the odds of miscarriage was J-shaped. Conclusion: There is a clear relationship between maternal heat exposure during the month preceding conception and miscarriage in our sub-Saharan African setting. Given the lack of feasible strategies to reduce pregnancy loss associated with prevailing high temperatures in sub-Saharan Africa, progressive climate change will likely exacerbate existing challenges for women’s reproductive health in this region.

Abstract Introduction Fishing populations constitute a suitable key population amongst which to conduct HIV prevention trials due to very high HIV prevalence and incidence, however, these are highly mobile populations. We determined the feasibility and acceptability of using fingerprinting and geographical positioning systems to describe mobility patterns and retention among fisherfolks on the shoreline of Lake Victoria in South-western Uganda. Methods Between August 2015 and January 2017, two serial cross-sectional surveys were conducted during which fingerprinting of all residents aged 18–30 years on the shoreline of Lake Victoria was done. A mapper moving ahead of the survey team, produced village maps and took coordinates of every household. These were accessed by the survey team that assigned household and individual unique identifiers (ID) and collected demographic data. Using the assigned IDs, individuals were enrolled and their fingerprints scanned. The fingerprinting was repeated 6 months later in order to determine the participant’s current household. If it was different from that at baseline, a new household ID was assigned which was used to map migrations both within and between villages. Results At both rounds, over 99% accepted to be fingerprinted. No fingerprinting faults were recorded at baseline and the level was under 1% at round two. Over 80% of the participants were seen at round two and of these, 16.3%, had moved to a new location whilst the majority, 85%, stayed within the same village. Movements between villages were mainly observed for those resident in large villages. Those who did not consider a fishing village to be their permanent home were less likely to be migrants than permanent residents (adjusted odds ratio = 0.37, 95%CI:0.15–0.94). Conclusion Use of fingerprinting in fishing populations is feasible and acceptable. It is possible to track this mobile population for clinical trials or health services using this technology since most movements could be traced within and between villages.

Abstract Background Periods of droughts can lead to decreased food security, and altered behaviours, potentially affecting outcomes on antiretroviral therapy (ART) among persons with HIV (PWH). We investigated whether decreased rainfall is associated with adverse outcomes among PWH on ART in Southern Africa. Methods Data were combined from 11 clinical cohorts of PWH in Lesotho, Malawi, Mozambique, South Africa, Zambia, and Zimbabwe, participating in the International epidemiology Databases to Evaluate AIDS Southern Africa (IeDEA-SA) collaboration. Adult PWH who had started ART prior to 01/06/2016 and were in follow-up in the year prior to 01/06/2016 were included. Two-year rainfall from June 2014 to May 2016 at the location of each HIV centre was summed and ranked against historical 2-year rainfall amounts (1981–2016) to give an empirical relative percentile rainfall estimate. The IeDEA-SA and rainfall data were combined using each HIV centre’s latitude/longitude. In individual-level analyses, multivariable Cox or generalized estimating equation regression models (GEEs) assessed associations between decreased rainfall versus historical levels and four separate outcomes (mortality, CD4 counts 400 copies/mL, and > 12-month gaps in follow-up) in the two years following the rainfall period. GEEs were used to investigate the association between relative rainfall and monthly numbers of unique visitors per HIV centre. Results Among 270,708 PWH across 386 HIV centres (67% female, median age 39 [IQR: 32–46]), lower rainfall than usual was associated with higher mortality (adjusted Hazard Ratio: 1.18 [95%CI: 1.07–1.32] per 10 percentile rainfall rank decrease) and unsuppressed viral loads (adjusted Odds Ratio: 1.05 [1.01–1.09]). Levels of rainfall were not strongly associated with CD4 counts 12-month gaps in care. HIV centres in areas with less rainfall than usual had lower numbers of PWH visiting them (adjusted Rate Ratio: 0.80 [0.66–0.98] per 10 percentile rainfall rank decrease). Conclusions Decreased rainfall could negatively impact on HIV treatment behaviours and outcomes. Further research is needed to explore the reasons for these effects. Interventions to mitigate the health impact of severe weather events are required.

Abstract Introduction In South Africa, the HIV care cascade remains suboptimal. We investigated the impact of small conditional financial incentives (CFIs) and male‐targeted HIV‐specific decision‐support application (EPIC‐HIV) on the HIV care cascade. Methods In 2018, in uMkhanyakude district, 45 communities were randomly assigned to one of four arms: (i) CFI for home‐based HIV testing and linkage to care within 6 weeks (R50 [US$3] food voucher each); (ii) EPIC‐HIV which are based on self‐determination theory; (iii) both CFI and EPIC‐HIV; and (iv) standard of care. EPIC‐HIV consisted of two components: EPIC‐HIV 1, provided to men through a tablet before home‐based HIV testing, and EPIC‐HIV 2, offered 1 month later to men who tested positive but had not yet linked to care. Linking HITS trial data to national antiretroviral treatment (ART) programme data and HIV surveillance programme data, we estimated HIV status awareness after the HITS trial implementation, ART status 3 month after the trial and viral load suppression 1 year later. Analysis included all known individuals living with HIV in the study area including those who did not participated in the HITS trial. Results Among the 33,778 residents in the study area, 2763 men and 7266 women were identified as living with HIV by the end of the intervention period and included in the analysis. After the intervention, awareness of HIV‐positive status was higher in the CFI arms compared to non‐CFI arms (men: 793/908 [87.3%] vs. 1574/1855 [84.9%], RR = 1.03 [95% CI: 0.99−1.07]; women: 2259/2421 [93.3%] vs. 4439/4845 [91.6%], RR = 1.02 [95% CI: 1.00−1.04]). Three months after the intervention, no differences were found for linkage to ART between arms. One year after the intervention, only 1829 viral test results were retrieved. Viral suppression was higher but not significant in the EPIC‐HIV intervention arms among men (65/99 [65.7%] vs. 182/308 [59.1%], RR = 1.11 [95% CI: 0.88−1.40]). Conclusions Small CFIs can contribute to achieve the first step of the HIV care cascade. However, neither CFIs nor EPIC‐HIV was sufficient to increase the number of people on ART. Additional evidence is needed to confirm the impact of EPIC‐HIV on viral suppression.

Abstract Background Most COVID-19 vulnerability indices rely on measures that are biased by rates of exposure or are retrospective like mortality rates that offer little opportunity for intervention. The Moore-Hill Vulnerability Index (MHVI) is a precision public health early warning alternative to traditional infection fatality rates that presents avenues for mortality prevention. Methods We produced an infection-severity vulnerability index by calculating the proportion of all recorded positive cases that were severe and attended by ambulances at small area scale for the East Midlands of the UK between May 2020 and April 2022. We produced maps identifying regions with high and low vulnerability, investigated the accuracy of the index over shorter and longer time periods, and explored the utility of the MHVI compared to other common proxy measures and indices. Analysis included exploring the correlation between our novel index and the Index of Multiple Deprivation (IMD). Results The MHVI captures geospatial dynamics that single metrics alone often overlook, including the compound health challenges associated with disadvantaged and declining coastal towns inhabited by communities with post-industrial health legacies. A moderate negative correlation between MHVI and IMD reflects spatial analysis which suggests that high vulnerability occurs in affluent rural as well as deprived coastal and urban communities. Further, the MHVI estimates of severity rates are comparable to infection fatality rates for COVID-19. Conclusions The MHVI identifies regions with known high rates of poor health outcomes prior to the pandemic that case rates or mortality rates alone fail to identify. Pre-hospital early warning measures could be utilised to prevent mortality during a novel pandemic.

Men in sub-Saharan Africa are less likely to accept HIV testing and link to HIV care than women. We conducted a trial to investigate the impact of conditional financial incentives and a decision support application, called EPIC-HIV, on HIV testing and linkage to care. We report the findings of the trial process evaluation to explore whether the interventions were delivered as intended, identify mechanisms of impact and any contextual factors that may have impacted the trial outcomes. Between August 2018 and March 2019, we conducted in-depth interviews and focus group discussions with trial participants (n = 31) and staff (n = 14) to examine views on the implementation process, participant responses to the interventions and the external factors that may have impacted the implementation and outcomes of the study. Interviews were audio-recorded, transcribed, and translated where necessary, and thematically analyzed using ATLAS-ti and NVivo. Both interventions were perceived to be acceptable and useful by participants and implementers. EPIC-HIV proved challenging to implement as intended because it was difficult to ensure consistent use of earphones, and maintenance of privacy. Some participants struggled to navigate the EPIC-HIV app independently and select stories that appealed to them without support. Some participants stopped exploring the app before the end, resulting in an incomplete use of EPIC-HIV. While the financial incentive was implemented as intended, there were challenges with eligibility. The convenience and privacy of home testing influenced the uptake of HIV testing. Contextual barriers including fear of HIV stigma and disclosure if diagnosed with HIV, and expectations of poor treatment in clinics may have inhibited linkage to care. Financial incentives were relatively straightforward to implement and increased uptake of home-based rapid HIV testing but were not sufficient as a 'stand-alone' intervention. Barriers like fear of stigma should be addressed to facilitate linkage to care.

Tuberculin skin test surveys in primary school children can be used to quantify Mycobacterium tuberculosis transmission at community level. KwaZulu-Natal province, South Africa, is home to 11.5 million people and suffers a burden of tuberculosis disease that is among the highest in the world. The last tuberculin survey in the province was undertaken in 1979. We performed a tuberculin skin test survey nested within a demographic and health household surveillance programme in Northern KwaZulu-Natal. We enrolled children aged between six and eight years of age attending primary schools in this community. Mixture analysis was used to determine tuberculin skin test thresholds and the Annual Risk of Tuberculous Infection derived from age at testing and infection prevalence. The Community Infection Ratio, a measure of the relative importance of within-household and community transmission, was calculated from data on tuberculin positivity disaggregated by household tuberculosis contact. Between June and December 2013, we obtained tuberculin skin test results on 1240 children. Mixture analysis proved unstable, suggesting two potential thresholds for test positivity. Using a threshold of ≥10mm or treating all non zero reactions as positive yielded estimates of the Annual Risk of Tuberculous Infection of 1.7% (1.4-2.1%) or 2.4% (2.0-3.0%). Using the same thresholds and including children reported to be receiving TB treatment as cases, resulted in estimates of 2.0% (1.6-2.5%) or 2.7% (2.2-3.3%). The Community Infection Ratio was 0.58 (0.33-1.01). The force of infection in this community is lower than that observed in Western Cape province, South Africa, but higher than that observed in community settings in most other parts of the world. Children in this community are commonly infected with Mycobacterium tuberculosis outside the home. Interventions to interrupt transmission are urgently needed.

South Africa rolled out dolutegravir (DTG) as first-line antiretroviral therapy (ART) in December 2019 to overcome high rates of pretreatment non-nucleoside reverse transcriptase inhibitor drug resistance. In the context of transition to DTG-based ART, this study spatiotemporally analysed detectable HIV viral loads (VLs) prior to- and following DTG rollout in public-sector healthcare facilities in KwaZulu-Natal (KZN) province, the epicentre of the HIV epidemic in South Africa. We retrospectively curated a HIV VL database using de-identified routine VL data obtained from the National Health Laboratory Service for the period January 2018 to June 2022. We analysed trends in HIV viraemia and mapped median log10 HIV VLs per facility on inverse distance weighted interpolation maps. We used Getis-Ord Gi* hotspot analysis to identify geospatial HIV hotspots. We obtained 7,639,978 HIV VL records from 736 healthcare facilities across KZN, of which 1,031,171 (13.5%) had detectable VLs (i.e., VLs ≥400 copies/millilitre (mL)). Of those with detectable VLs, we observed an overall decrease in HIV VLs between 2018 and 2022 (median 4.093 log10 copies/mL; 95% confidence interval (CI) 4.087-4.100 to median 3.563 log10 copies/mL; CI 3.553-3.572), p

Introduction As people living with HIV (PLHIV) are experiencing longer survival, the co-occurrence of HIV and non-communicable diseases has become a public health priority. In response to this emerging challenge, we aimed to characterise the spatial structure of convergence of chronic health conditions in an HIV hyperendemic community in KwaZulu-Natal, South Africa.Methods In this cross-sectional study, we used data from a comprehensive population-based disease survey conducted in KwaZulu-Natal, South Africa, which collected data on HIV, diabetes and hypertension. We implemented a novel health needs scale to categorise participants as: diagnosed and well-controlled (Needs Score 1), diagnosed and suboptimally controlled (Score 2), diagnosed but not engaged in care (Score 3) or undiagnosed and uncontrolled (Score 4). Scores 2–4 were indicative of unmet health needs. We explored the geospatial structure of unmet health needs using different spatial clustering methods.Results The analytical sample comprised 18 041 individuals. We observed a similar spatial structure for HIV among those with combined needs Score 2–3 (diagnosed but uncontrolled) and Score 4 (undiagnosed and uncontrolled), with most PLHIV with unmet needs clustered in the southern urban and peri-urban areas. Conversely, a high prevalence of need Scores 2 and 3 for diabetes and hypertension was mostly distributed in the more rural central and northern part of the surveillance area. A high prevalence of need Score 4 for diabetes and hypertension was mostly distributed in the rural southern part of the surveillance area. Multivariate clustering analysis revealed a significant overlap of all three diseases in individuals with undiagnosed and uncontrolled diseases (unmet needs Score 4) in the southern part of the catchment area.Conclusions In an HIV hyperendemic community in South Africa, areas with the highest needs for PLHIV with undiagnosed and uncontrolled disease are also areas with the highest burden of unmet needs for other chronic health conditions, such as diabetes and hypertension. Our study has revealed remarkable differences in the distribution of health needs across the rural to urban continuum even within this relatively small study site. The identification and prioritisation of geographically clustered vulnerable communities with unmet health needs for both HIV and non-communicable diseases provide a basis for policy and implementation strategies to target communities with the highest health needs.

ABSTRACTSouth Africa is faced with a high HIV and STI prevalence and incidence, respectively, with pockets of high burden areas driving these diseases. Localised monitoring of the HIV epidemic and STI endemic would enable more effective targeted prevention strategies. We assessed spatial variations in curable STI incidence among a cohort of women enrolled in HIV prevention clinical trials between 2002 and 2012. STI incidence rates from 7557 South African women enrolled in five HIV prevention trials were geo-mapped using participant household GPS coordinates. Age and period standardised incidence rates were calculated for 43 recruitment areas and Bayesian conditional autoregressive areal spatial regression (CAR) was used to identify significant patterns and spatial patterns of STI infections in recruitment communities. Overall age and period standardised STI incidence rate were estimated as 15 per 100 PY and ranged from 6 to 24 per 100 PY. We identified five significant STI high risk areas with higher-than-expected incidence of STIs located centrally (three-locations) and southern neighbouring areas of Durban (two-locations). Younger age (

Background Early infant diagnosis (EID) for HIV-exposed infants is essential due to high mortality during the first months of their lives. In Conakry (Guinea), timely EID is difficult as traffic congestion prevents the rapid transport of blood samples to the central laboratory. We investigated the cost-effectiveness of transporting EID blood samples by unmanned aerial vehicles (UAV), also known as drones.Methods and findings Using Monte Carlo simulations, we conducted a cost-effectiveness comparative analysis between EID blood samples transportation by on-demand UAV transportation versus the baseline scenario (ie, van with irregular collection schedules) and compared with a hypothetic on-demand motorcycle transportation system. Incremental cost-effectiveness ratio (ICER) per life-year gained was computed. Simulation models included parameters such as consultation timing (eg, time of arrival), motorcycle and UAV characteristics, weather and traffic conditions. Over the 5-year period programme, the UAV and motorcycle strategies were able to save a cumulative additional 834.8 life-years (585.1–1084.5) and 794.7 life-years (550.3–1039.0), respectively, compared with the baseline scenario. The ICER per life-year gained found were US$535 for the UAV strategy versus baseline scenario, US$504 for the motorcycle strategy versus baseline scenario and US$1137 per additional life-year gained for the UAV versus motorcycle strategy. Respectively, those ICERs represented 44.8%, 42.2% and 95.2% of the national gross domestic product (GDP) per capita in Guinea—that is, US$1194.Conclusion Compared with the baseline strategy, both transportation of EID blood samples by UAVs or motorcycles had a cost per additional life-year gained below half of the national GDP per capita and could be seen as cost-effective in Conakry. A UAV strategy can save more lives than a motorcycle one although the cost needed per additional life-year gained might need to consider alongside budget impact and feasibility considerations.

Key points Our study found that there are substantial differences in time to reimbursement of pembrolizumab for the same conditions in different countries, with NICE and The National Advisory Committee for the Basket of Health Services in Israel approving one condition at the same time, Israel approving two conditions earlier than NICE, and PBAC lagging behind for every condition. These differences could be due to the differences in health policy systems and the many factors that affect reimbursement. Comparing the reimbursement process between different countries can highlight the challenges facing their health systems in early adoption of new treatments.

Background: The reason why Black and South Asian healthcare workers are at a higher risk for SARS-CoV-2 infection remain unclear. We aimed to quantify the risk for SARS-CoV-2 infection among healthcare staff who belong to the ethnic minority and elucidate pathways of infection. Methods: A one-year follow-up retrospective cohort study has been conducted among National Health Service employees who were working at 123 facilities in Lincolnshire, UK. Results: Overall, 13,366 professionals were included. SARS-CoV-2 incidence per person-year was 5.2% (95% CI: 3.6–7.6%) during the first COVID-19 wave (January–August 2020) and 17.2% (13.5–22.0%) during the second wave (September 2020–February 2021). Compared with White staff, Black and South Asian employees were at higher risk for SARS-CoV-2 infection during both the first wave (hazard ratio, HR 1.58 [0.91–2.75] and 1.69 [1.07–2.66], respectively) and the second wave (HR 2.09 [1.57–2.76] and 1.46 [1.24–1.71]). Higher risk for SARS-CoV-2 infection persisted even after controlling for age, sex, pay grade, residence environment, type of work, and time exposure at work. Higher adjusted risk for SARS-CoV-2 infection were also found among lower-paid health professionals. Conclusion: Black and South Asian health workers continue to be at higher risk for SARS-CoV-2 infection than their White counterparts. Urgent interventions are required to reduce SARS-CoV-2 infection in these ethnic groups.

Abstract Introduction While it is widely acknowledged that family relationships can influence health outcomes, their impact on the uptake of individual health interventions is unclear. In this study, we quantified how the efficacy of a randomized health intervention is shaped by its pattern of distribution in the family network. Methods The “Home‐Based Intervention to Test and Start” (HITS) was a 2×2 factorial community‐randomized controlled trial in Umkhanyakude, KwaZulu‐Natal, South Africa, embedded in the Africa Health Research Institute's population‐based demographic and HIV surveillance platform (ClinicalTrials.gov # NCT03757104). The study investigated the impact of two interventions: a financial micro‐incentive and a male‐targeted HIV‐specific decision support programme. The surveillance area was divided into 45 community clusters. Individuals aged ≥15 years in 16 randomly selected communities were offered a micro‐incentive (R50 [$3] food voucher) for rapid HIV testing (intervention arm). Those living in the remaining 29 communities were offered testing only (control arm). Study data were collected between February and November 2018. Using routinely collected data on parents, conjugal partners, and co‐residents, a socio‐centric family network was constructed among HITS‐eligible individuals. Nodes in this network represent individuals and ties represent family relationships. We estimated the effect of offering the incentive to people with and without family members who also received the offer on the uptake of HIV testing. We fitted a linear probability model with robust standard errors, accounting for clustering at the community level. Results Overall, 15,675 people participated in the HITS trial. Among those with no family members who received the offer, the incentive's efficacy was a 6.5 percentage point increase (95% CI: 5.3−7.7). The efficacy was higher among those with at least one family member who received the offer (21.1 percentage point increase (95% CI: 19.9−22.3). The difference in efficacy was statistically significant (21.1–6.5 = 14.6%; 95% CI: 9.3−19.9). Conclusions Micro‐incentives appear to have synergistic effects when distributed within family networks. These effects support family network‐based approaches for the design of health interventions.

Abstract Globally, South Africa hosts the highest number of people living with HIV (PLHIV) and the unique legacy of internal labour migration continues to be a major driver of the regional epidemic, interrupting treatment-as-prevention efforts. The study examined levels, trends, and predictors of migration in rural KwaZulu-Natal Province, South Africa, using population-based surveillance data from 2005 through 2017. We followed 69 604 adult participants aged 15–49 years and recorded their migration events (i.e., out-migration from the surveillance area) in 423 038 person-years over 525 397 observations. Multiple failure Cox-regression models were used to measure the risk of migration by socio-demographic factors: age, sex, educational status, marital status, HIV, and community antiretroviral therapy (ART) coverage. Overall, 69% of the population cohort experienced at least one migration event during the follow-up period. The average incidence rate of migration was 9.96 events and 13.23 events per 100 person-years in women and men, respectively. Migration rates declined from 2005 to 2008 then peaked in 2012 for both women and men. Adjusting for other covariates, the risk of migration was 3.4-times higher among young women aged 20–24 years compared to those aged ≥ 40 years (adjusted Hazard Ratio [aHR] = 3.37, 95% Confidence Interval [CI]: 3:19–3.57), and 2.9-times higher among young men aged 20–24 years compared to those aged ≥ 40 years (aHR = 2.86, 95% CI:2.69–3.04). There was a 9% and 27% decrease in risk of migration among both women (aHR = 0.91, 95% CI: 0.83 – 0.99) and men (aHR = 0.73, 95% CI 0.66 – 0.82) respectively per every 1% increase in community ART coverage. Young unmarried women including those living with HIV, migrated at a magnitude similar to that of their male counterparts, and lowered as ART coverage increased over time, reflecting the role of improved HIV services across space in reducing out-migration. A deeper understanding of the characteristics of a migrating population provides critical information towards identifying and addressing gaps in the HIV prevention and care continuum in an era of high mobility.

Abstract Background Antiretroviral therapy (ART) through universal test and treat (UTT) and HIV pre-exposure prophylaxis (PrEP) substantially reduces HIV-related mortality, morbidity and incidence. Effective individual-level prevention modalities have not translated into population-level impact in southern Africa due to sub-optimal coverage among adolescents and youth who are hard to engage. We aim to investigate the feasibility, acceptability, and preliminary population level effectiveness of HIV prevention services with or without peer support to reduce prevalence of transmissible HIV amongst adolescents and young adults in KwaZulu-Natal. Methods We are conducting a 2 × 2 factorial trial among young men and women aged 16–29 years, randomly selected from the Africa Health Research Institute demographic surveillance area. Participants are randomly allocated to one of four intervention combinations: 1) Standard of Care (SOC): nurse-led services for HIV testing plus ART if positive or PrEP for those eligible and negative; 2) Sexual and Reproductive Health (SRH): Baseline self-collected vaginal and urine samples with study-organized clinic appointments for results, treatment and delivery of HIV testing, ART and PrEP integrated with SRH services; 3) Peer-support: Study referral of participants to a peer navigator to assess their health, social and educational needs and provide risk-informed HIV prevention, including facilitating clinic attendance; or 4) SRH + peer-support. The primary outcomes for effectiveness are: (1) the proportion of individuals with infectious HIV at 12 months and (2) uptake of risk-informed comprehensive HIV prevention services within 60 days of enrolment. At 12 months, all participants will be contacted at home and the study team will collect a dried blood spot for HIV ELISA and HIV viral load testing. Discussion This trial will enable us to understand the relative importance of SRH and peer support in creating demand for effective and risk informed biomedical HIV prevention and preliminary data on their effectiveness on reducing the prevalence of transmissible HIV amongst all adolescents and youth. Trial registration Trial Registry: clincialtrials.gov. ClinicalTrials.gov Identifier NCT04532307 . Registered: March 2020.

Valid screening and diagnostic algorithms are needed to achieve 2030 targets proposed by the WHO's Global Diabetes Compact. We explored anthropometric thresholds to optimally screen and refer individuals for diabetes testing in rural South Africa. We evaluated screening thresholds for waist circumference (WC), body mass index (BMI), and waist-hip ratio (WHR) to detect dysglycemia based on a glycated hemoglobin (HbA1C) ≥6.5% among adults in a population-based study in South Africa using weighted, non-parametric ROC regression analyses. We then assessed the diagnostic validity of traditional obesity thresholds, explored optimal thresholds for this population, and fit models stratified by sex, age, and HIV status. The prevalence of dysglycemia in the total study population (n = 17,846) was 7.7%. WC had greater discriminatory capacity than WHR to detect dysglycemia in men (p-value81cm) performed well (sensitivity 91%, positive predictive value [PPV] 14.9%), substantially lower thresholds were needed to achieve acceptable sensitivity and PPV among men (traditional >94cm, derived >79.5cm). WC outperforms BMI as an anthropometric screening measure for dysglycemia in rural South Africa. Whereas WC guideline thresholds are appropriate for women, male-derived WC cutoffs performed better at lower thresholds. In this rural South African population, thresholds that maximize specificity and PPV for efficient resource allocation may be preferred.

Abstract Introduction Interruptions in treatment pose risks for people with HIV (PWH) and threaten progress in ending the HIV epidemic; however, the COVID‐19 pandemic's impact on HIV service delivery across diverse settings is not broadly documented. Methods From September 2020 to March 2021, the International epidemiology Databases to Evaluate AIDS (IeDEA) research consortium surveyed 238 HIV care sites across seven geographic regions to document constraints in HIV service delivery during the first year of the pandemic and strategies for ensuring care continuity for PWH. Descriptive statistics were stratified by national HIV prevalence (

Background: There is an alarming trend in sub-Saharan Africa in the use of codeine-containing pharmaceuticals, but its risk of common comorbidities, such as mental health, remains unquantified at a national-level. We investigated the relationship between codeine use and onset of depression in South Africa at a population-level. Methods: We used nationally representative panel data from the South Africa National Income Dynamic Study to investigate the relationship between exposure to codeine use in the community (i.e. residing in a codeine hotspot) and onset of depression. Geographical hotspots of codeine use were identified using Kulldorff spatial scan statistic in SaTScan. We quantified depression onset at Wave 5 (year 2017) between individuals residing inside and outside a codeine hotspot who were depression-free at enrolment (Wave 4: 2015) using generalised estimating equation (GEE) regression models. Results: We identified four statistically significant hotspots of codeine use, mostly located at the northern part of the country. Among 13,020 participants who were depression-free at enrolment, residing within a codeine use hotspot was significantly associated with higher subsequent onset of depression (aRR=1.21, 95% CI:1.08-1.44). Limitations: Data on diagnosis of depressive disorder were not available. Conclusion: South Africa, a resource scarce nation with chronically limited mental health services, is not spared from the global opioid epidemic and its impact on depression. Targeted scale-up access to agonist therapy to effectively treat (opioid) addiction in communities at risk for high exposure to codeine use could reduce the risk of subsequent mental health challenges.

The scaling up of antiretroviral therapy services over the past decades has led to a remarkable reduction in HIV infections and HIV-related deaths in South Africa (SA). While this is a step in the right direction, it brings a new public health challenge into focus, namely psychological challenges associated with such chronic and often stigmatising condition in SA, home to the largest HIV epidemic. Given the current lack of national-level evidence, we investigated the role of the HIV epidemic on depression onset in SA using nationally representative panel data from the South African National Income Dynamics Study (SA-NIDS). Our incident cohort consisted of 13,020 sampled adult participants who were depression-free in Wave 4 (baseline year of 2015). We then measured the risk of depression onset in Wave 5 (year 2017) based on the level of HIV prevalence in the community where study participants resided at baseline. A High-resolution map of HIV spatial heterogeneity (i.e., community HIV prevalence) was generated using ordinary kriging mapping methods from a separate nationally representative data source that corresponded to the investigation period. Geospatial analyses were conducted to identify the spatial structure of HIV and depression onset, and generalised estimating equations (GEE) regression models were fitted to determine the risk of depression onset over time based on community HIV prevalence. Our geospatial analyses indicated that HIV and depression onset prevalence spatially overlapped in the eastern part of the country, particularly in Gauteng, KwaZulu-Natal, Mpumalanga, and Free State province. The GEE regression analyses indicated that individual residency in a community with high HIV prevalence was significantly associated with a higher risk of depression than a low HIV prevalence community (adjusted odds ratio =1.45, 95% CI=1.12-1.48). For the first time, we identified a geospatial overlap between HIV and depression, with a greater risk of depression onset in high HIV prevalence communities, at a national scale in SA. There is a need for place-based policy interventions that prioritise the availability of and access to mental health services in high HIV prevalent SA communities, in an ageing HIV epidemic.

Abstract We use a regression discontinuity design to estimate the causal effect of antiretroviral therapy (ART) eligibility according to national treatment guidelines of South Africa on two risk factors for cardiovascular disease, body mass index (BMI) and blood pressure. We combine survey data collected in 2010 in KwaZulu-Natal, South Africa, with clinical data on ART. We find that early ART eligibility significantly reduces systolic and diastolic blood pressure. We do not find any significant effects on BMI. The effect on blood pressure can be detected up to three years after becoming eligible for ART.

Abstract The role of geographical disparities of health-related risk factors with anemia are poorly documented for women of reproductive age in sub-Saharan Africa (SSA). We aimed to determine the contribution of potential factors and to identify areas at higher risk of anemia for women in reproductive age in SSA. Our study population comprised 27 nationally representative samples of women of reproductive age (15–49) who were enrolled in the Demographic and Health Surveys and conducted between 2010 and 2019 in SSA. Overall, we found a positive association between being anemic and the ecological exposure to malaria incidence [adjusted odds ratio (AOR) = 1.02, 95% confidence interval (CI) 1.02–1.02], and HIV prevalence (AOR = 1.01, CI 1.01–1.02). Women currently pregnant or under deworming medication for the last birth had 31% (AOR = 1.31, CI 1.24–1.39) and 5% (AOR = 1.05, CI 1.01–1.10) higher odds of having anemia, respectively. Similarly, women age 25–34 years old with low education, low income and living in urban settings had higher odds of having anemia. In addition, underweight women had 23% higher odds of suffering anemia (AOR = 1.23, CI 1.15–1.31). Females with low levels of education and wealth index were consistently associated with anemia across SSA. Spatial distribution shows increased risk of anemia in Central and Western Africa. Knowledge about the contribution of known major drivers and the spatial distribution of anemia risk can mitigate operational constraints and help to design geographically targeted intervention programs in SSA.

Abstract Background HIV affects many adolescent girls and young women (AGYW) in South Africa. Given the bi-directional HIV and mental health relationship, mental health services may help prevent and treat HIV in this population. We therefore examined the association between common mental disorders (CMD) and HIV-related behaviours and service utilisation, in the context of implementation of the combination DREAMS (Determined, Resilient, Empowered, AIDS-free, Mentored and Safe) HIV prevention programme in rural uMkhanyakude district, KwaZulu-Natal. DREAMS involved delivering a package of multiple interventions in a single area to address multiple sources of HIV risk for AGYW. Methods We analysed baseline data from an age-stratified, representative cohort of 13–22 year-old AGYW. We measured DREAMS uptake as a count of the number of individual-level or community-based interventions each participant received in the last 12 months. CMD was measured using the validated Shona Symptom Questionnaire, with a cut off score ≥ 9 indicating probable CMD. HIV status was ascertained through home-based serotesting. We used logistic regression to estimate the association between CMD and HIV status adjusting for socio-demographics and behaviours. Results Probable CMD prevalence among the 2184 respondents was 22.2%, increasing steadily from 10.1% among 13 year-old girls to 33.1% among 22 year-old women. AGYW were more likely to report probable CMD if they tested positive for HIV (odds ratio vs. test negative: 1.88, 95% confidence interval: 1.40–2.53). After adjusting for socio-demographics and behaviours, there was evidence that probable CMD was more prevalent among respondents who reported using multiple healthcare-related DREAMS interventions. Conclusion We found high prevalence of probable CMD among AGYW in rural South Africa, but it was only associated with HIV serostatus when not controlling for HIV acquisition risk factors. Our findings highlight that improving mental health service access for AGYW at high risk for HIV acquisition might protect them. Interventions already reaching AGYW with CMD, such as DREAMS, can be used to deliver mental health services to reduce both CMD and HIV risks. There is a need to integrate mental health education into existing HIV prevention programmes in school and communities.

The widespread psychological effects of contagion mitigation measures associated with the novel coronavirus disease 2019 (COVID-19) are well known. Phases of “lockdown” have increased levels of anxiety and depression globally. Most research uses methods such as self-reporting that highlight the greater impact of the pandemic on the mental health of females. Emergency medical data from ambulance services may be a better reflection of male mental health. We use ambulance data to identify unusual clusters of high rates of male mental health emergencies occurring in the East Midlands of the United Kingdom during the first national “lockdown” and to explore factors that may explain clusters. Analysis of more than 5,000 cases of male mental health emergencies revealed 19 unusual spatial clusters. Binary logistic regression analysis (χ 2 = 787.22, df = 20, p ≤ .001) identified 16 factors that explained clusters, including proximity to “healthy” features of the physical landscape, urban and rural dynamics, and socioeconomic condition. Our findings suggest that the factors underlying vulnerability of males to severe mental health conditions during “lockdown” vary within and between rural and urban spaces, and that the wider “hinterland” surrounding clusters influences the social and physical access of males to services that facilitate mental health support. Limitations on social engagement to mitigate effects of the pandemic are likely to continue. Our approach could inform delivery of emergency services and the development of community-level services to support vulnerable males during periods of social isolation.

The novel coronavirus disease 2019 (COVID-19) pandemic and associated mitigation strategies such as “lockdown” are having widespread adverse psychological effects, including increased levels of anxiety and depression. Most research using self-reported data highlights the pandemic’s impact on the psychological well-being of females, whereas data for mental health emergency presentations may reflect the impact on male mental health more accurately. We analyzed records of male mental health emergencies occurring in the East Midlands of the United Kingdom during the first national “lockdown.” We computed two binary logistic regression models to (a) compare male mental health emergencies occurring during “lockdown,” 2020 (5,779) with those occurring in the same period in 2019 ( N = 4,744) and (b) compare male ( N = 5,779) and female ( N = 7,695) mental health emergencies occurring during “lockdown.” Comparisons considered the characteristics of mental health emergencies recorded by ambulance clinicians (Primary Impressions), and the socioeconomic characteristics of communities where emergencies use the Index of Multiple Deprivation. We found that during “lockdown,” male emergencies were more likely to involve acute anxiety (odds ratio [OR]: 1.42) and less likely to involve intentional drug overdose (OR: 0.86) or attempted suicide (OR: 0.71) compared with 2019. Compared with females, male emergencies were more likely to involve acute behavioral disturbance (OR: 1.99) and less likely to involve anxiety (OR: 0.67), attempted suicide (OR: 0.83), or intentional drug overdose (OR: 0.76). Compared with 2019, and compared with females, males experiencing mental health emergencies during “lockdown” were more likely to present in areas of high deprivation. Understanding the presentation of male mental health emergencies could inform improved patient care pathways.

Abstract Background Ad hoc assumptions about the unobserved infection event, which is known only to occur between the latest-negative and earliest-positive test dates, can lead to biased HIV incidence rate estimates. Using a G-imputation approach, we infer the infection dates from covariate data to estimate the HIV incidence rate in a hyper-endemic South African setting. Methods A large demographic surveillance system has annually tested a cohort of HIV-uninfected participants living in the KwaZulu-Natal province. Using this data, we estimated a cumulative baseline hazard function and the effects of time-dependent covariates on the interval censored infection dates. For each HIV-positive participant in the cohort, we derived a cumulative distribution function and sampled multiple infection dates conditional on the unique covariate values. We right censored the data at the imputed dates, calculated the annual HIV incidence rate per 100 person-years, and used Rubin’s rules to obtain the 95% confidence intervals. Results A total of 20,011 uninfected individuals with a repeat HIV test participated in the incidence cohort between 2005 and 2018. We observed 2,603 infections per 58,769 person-years of follow-up among women and 845 infections per 41,178 person-years of follow-up among men. Conditional on age and circumcision status (men only), the female HIV incidence rate declined by 25%, from 5.0 to 3.7 infections per 100 person-years between 2014 and 2018. During this period, the HIV incidence rate among men declined from 2.1 to 1.1 infections per 100 person-years—a reduction of 49%. We observed similar reductions in male and female HIV incidence conditional on condom-use, marital status, urban residential status, migration history, and the HIV prevalence in the surrounding community. Conclusion We have followed participants in one of the world’s largest and longest running HIV cohorts to estimate long-term trends in the population-wide incidence of infection. Using a G-imputation approach, we present further evidence for HIV incidence rate declines in this hyper-endemic South African setting.

Abstract Background Insecticide-treated net (ITN) use is the core intervention among the strategies against malaria in sub-Saharan Africa (SSA) and the percentage of ITN ownership has increased from 47% in 2010 to 72% in 2017 across countries in SSA. Regardless of this massive expansion of ITN distribution, considerable gap between ownership and use of ITNs has been reported. Using data from more than 100,000 households in Central and East Africa (CEA) countries, the main aim of this study was to identify barriers associated with low ITN use and conduct geospatial analyses to estimate numbers and locations of vulnerable children living in areas with high malaria and low ITN use. Methods Main sources of data for this study were the Demographic and Health Surveys and Malaria Indicator Surveys conducted in 11 countries in CEA. Logistic regression models for each country were built to assess the association between ITN ownership or ITN use and several socioeconomic and demographic variables. A density map of children under 5 living in areas at high-risk of malaria and low ITN use was generated to estimate the number of children who are living in these high malaria burden areas. Results Results obtained suggest that factors such as the number of members in the household, total number of children in the household, education and place of residence can be key factors linked to the use of ITN for protecting children against malaria in CEA. Results from the spatiotemporal analyses found that although total rates of ownership and use of ITNs across CEA have increased up to 70% and 48%, respectively, a large proportion of children under 5 (19,780,678; 23% of total number of children) still lives in high-risk malaria areas with low use of ITNs. Conclusion The results indicate that despite substantial progress in the distribution of ITNs in CEA, with about 70% of the households having an ITN, several socioeconomic factors have compromised the effectiveness of this control intervention against malaria, and only about 48% of the households protect their children under 5 with ITNs. Increasing the effective ITN use by targeting these factors and the areas where vulnerable children reside can be a core strategy meant to reducing malaria transmission.

Understanding spatial configuration of sexual network structure is critical for effective use of HIV preventative interventions in a community. However, this has never been described at the population level for any setting in sub-Saharan Africa. We constructed the comprehensive geospatial sexual network among new heterosexual partnerships in rural KwaZulu-Natal, South Africa. In the Africa Health Research Institute (AHRI)'s population-based surveillance, we identified stable sexual partnerships among individuals (≥15 years) from 2003 to 2016. Sexual partnerships and residency were recorded via household surveys (every 4-6 months). We geolocated residents and migration events and mapped the geospatial linkages of sexual partners at the start of sexual partnerships. In a grid composed by 108 cells (nodes; 3kmx3km per cell) covering the surveillance area (438km2), we calculated the degree of connectivity and centrality of the nodes and examined their association with HIV prevalence and incidence per cell. Of 2401 new sexual partnerships, 21% (n = 495) had both partners living within the surveillance area at the start of sexual partnerships, and 76% (376/495) were linked to the geographic HIV cluster with high HIV prevalence identified in a peri-urban community. Overall, 57 nodes had at least one connection to another node. The nodes in the peri-urban cluster had higher connectivity (mean = 19, range: 9-32), compared to outside the cluster (6, range: 1-16). The node's degree of connectivity was positively associated with HIV prevalence of the cell (Pearson correlation coefficient = 0.67; p

In this study, we hypothesize that HIV geographical clusters (geospatial areas with significantly higher numbers of HIV positive individuals) can behave as the highly connected nodes in the transmission network. Using data come from one of the most comprehensive demographic surveillance systems in Africa, we found that more than 70% of the HIV transmission links identified were directly connected to an HIV geographical cluster located in a peri-urban area. Moreover, we identified a single central large community of highly connected nodes located within the HIV cluster. This module was composed by nodes highly connected among them, forming a central structure of the network that was also connected with the small sparser modules located outside of the HIV geographical cluster. Our study supports the evidence of the high level of connectivity between HIV geographical high-risk populations and the entire community.

Here, the authors investigate the outcome of prevention services scale-up on HIV incidence in a South African large population-based HIV surveillance cohort with over a decade of follow-up and associate a 43% reduction in incidence to earlier male medical circumcision and increased levels of antiretroviral therapy coverage.

Summary: Background: There has been remarkable progress in the treatment of HIV throughout sub-Saharan Africa, but there are few data on the prevalence and overlap of other significant causes of disease in HIV endemic populations. Our aim was to identify the prevalence and overlap of infectious and non-communicable diseases in such a population in rural South Africa. Methods: We did a cross-sectional study of eligible adolescents and adults from the Africa Health Research Institute demographic surveillance area in the uMkhanyakude district of KwaZulu-Natal, South Africa. The participants, who were 15 years or older, were invited to participate at a mobile health camp. Medical history for HIV, tuberculosis, hypertension, and diabetes was established through a questionnaire. Blood pressure measurements, chest x-rays, and tests of blood and sputum were taken to estimate the population prevalence and geospatial distribution of HIV, active and lifetime tuberculosis, elevated blood glucose, elevated blood pressure, and combinations of these. Findings: 17 118 adolescents and adults were recruited from May 25, 2018, to Nov 28, 2019, and assessed. Overall, 52·1% (95% CI 51·3–52·9) had at least one active disease. 34·2% (33·5–34·9) had HIV, 1·4% (1·2–1·6) had active tuberculosis, 21·8% (21·2–22·4) had lifetime tuberculosis, 8·5% (8·1–8·9) had elevated blood glucose, and 23·0% (22·4–23·6) had elevated blood pressure. Appropriate treatment and optimal disease control was highest for HIV (78·1%), and lower for elevated blood pressure (42·5%), active tuberculosis (29·6%), and elevated blood glucose (7·1%). Disease prevalence differed notably by sex, across age groups, and geospatially: men had a higher prevalence of active and lifetime tuberculosis, whereas women had a substantially high prevalence of HIV at 30–49 years and an increasing prevalence of multiple and poorly controlled non-communicable diseases when older than 50 years. Interpretation: We found a convergence of infectious and non-communicable disease epidemics in a rural South African population, with HIV well treated relative to all other diseases, but tuberculosis, elevated blood glucose, and elevated blood pressure poorly diagnosed and treated. A public health response that expands the successes of the HIV testing and treatment programme to provide multidisease care targeted to specific populations is required to optimise health in such settings in sub-Saharan Africa. Funding: Wellcome Trust, Bill & Melinda Gates Foundation, the South African Department of Science and Innovation, South African Medical Research Council, and South African Population Research Infrastructure Network. Translation: For the isiZulu translation of the abstract see Supplementary Materials section.

Background The most immediate response of the research community to COVID-19 has been a focus on understanding the effects, treatment and prevention of infection. Of equal and ongoing importance is elucidating the impact of mitigation measures, such as lockdown, on the well-being of societies. Research about mental health and lockdown in the UK has predominately involved large surveys that are likely to encounter self-selection bias. Further, self-reporting does not constitute a clinical judgement. Aims To (a) compare the age, gender and ethnicity of patients experiencing mental health emergencies prior compared with during lockdown, (b) determine whether the nature of mental health emergencies has changed during compared with before lockdown, (c) explore the utility of emergency medical service data for identifying vulnerability to mental health emergencies in real time during a pandemic. Method A total of 32 401 clinical records of ambulance paramedics attending mental health emergencies in the East Midlands of the UK between 23 March and 31 July 2020 and the same period in 2019 were analysed using binary logistic regression. Results People of younger age, male gender and South Asian and Black ethnicity are particularly vulnerable to acute mental health conditions during lockdown. Patients with acute cases of anxiety have increased during lockdown whereas suicide and intentional drug overdose have decreased. Conclusions Self-reported data may underrepresent the true impact of lockdown on male mental health and ethnic minority groups. Emergency medical data can be used to identify vulnerable communities in the context of the extraordinary circumstances surrounding the current pandemic, as well as under more ordinary circumstances.

Abstract Background Fine scale geospatial analysis of HIV infection patterns can be used to facilitate geographically targeted interventions. Our objective was to use the geospatial technology to map age and time standardized HIV incidence rates over a period of 10 years to identify communities at high risk of HIV in the greater Durban area. Methods HIV incidence rates from 7557 South African women enrolled in five community-based HIV prevention trials (2002–2012) were mapped using participant household global positioning system (GPS) coordinates. Age and period standardized HIV incidence rates were calculated for 43 recruitment clusters across greater Durban. Bayesian conditional autoregressive areal spatial regression (CAR) was used to identify significant patterns and clustering of new HIV infections in recruitment communities. Results The total person-time in the cohort was 9093.93 years and 613 seroconversions were observed. The overall crude HIV incidence rate across all communities was 6·74 per 100PY (95% CI: 6·22–7·30). 95% of the clusters had HIV incidence rates greater than 3 per 100PY. The CAR analysis identified six communities with significantly high HIV incidence. Estimated relative risks for these clusters ranged from 1.34 to 1.70. Consistent with these results, age standardized HIV incidence rates were also highest in these clusters and estimated to be 10 or more per 100 PY. Compared to women 35+ years old younger women were more likely to reside in the highest incidence areas (aOR: 1·51, 95% CI: 1·06–2·15; aOR: 1.59, 95% CI: 1·19–2·14 and aOR: 1·62, 95% CI: 1·2–2·18 for

Abstract Background Despite increased antiretroviral therapy (ART) coverage, the incidence of HIV infection among women in rural South Africa remains high. While many socio-demographic and behavioral factors have been identified, the effect of female migration intensity on the risk of HIV acquisition before and after ART scale-up has not been evaluated in the country. Methods We followed 13,315 female participants aged 15–49 who were HIV-uninfected at baseline and recorded their migration events between 2004 and 2015. Using a Cox proportional hazard model, we estimated the time to HIV acquisition among the women, adjusting for annual migration intensity (high: ≥2 events/year, moderate = 1 event/year, and low = 0 event/year) before and after ART scale-up in 2010. Results 1998 (15%) new HIV-infection events were recorded during the observation period. Overall, high migration intensity was associated with an increased HIV acquisition risk among women when compared with low migration intensity (HR = 2.88, 95% CI: 1.56–5.53). Among those with high migration intensity, the risk of HIV acquisition was significantly lower in the post-ART period compared to the pre-ART period, after controlling for key socio-demographic and behavioural covariates (aHR = 0.18, 95% CI 0.04–0.83). Conclusions Women who migrated frequently after ART scale-up had a significantly reduced HIV acquisition risk compared to those before its implementation. While this reduction is encouraging, women who migrate frequently remain at high risk of HIV acquisition. In the era of ART, there remains a critical need for public health interventions to reduce the risk of HIV acquisition in this highly vulnerable population.

Introduction Despite progress towards the Joint United Nations Programme on HIV/AIDS 95-95-95 targets, South Africa is still suffering from one of the largest HIV epidemics globally. In this study, we generated high-resolution HIV prevalence maps and identified people living with HIV (PLHIV) in underserved areas to provide essential information for the optimal allocation of HIV-related services.Methods The data come from the South Africa Demographic and Health Survey conducted in 2016 and spatial variables from other published literature. We produced high-resolution maps of HIV prevalence and underserved areas, defined as a greater than 30 min travel time to the nearest healthcare facility. Using these maps and the population density, we mapped PLHIV and the PLHIV within underserved areas for 30, 60 and 120 min thresholds.Results There was substantial geographic variation in HIV prevalence, ranging from 1.4% to 24.2%, with a median of 11.5% for men, and from 2.1% to 48.1%, with a median of 20.6% for women. Gauteng province showed the highest density for both HIV prevalence and PLHIV. 80% of all areas in the country were identified as underserved areas (30 min threshold), which contained more than 16% and 20% of the total men and women living with HIV, respectively. KwaZulu-Natal province had the largest number of PLHIV in underserved areas (30 min threshold) and showed less than one healthcare facility per 1000 PLHIV.Conclusion Our study showed extensive spatial variation of HIV prevalence and significant numbers of PLHIV in underserved areas in South Africa. Moreover, we identified locations where HIV-related services need to be intensified to reach the ~1.5 million PLHIV in underserved areas, particularly in KwaZulu-Natal province, with less than one healthcare facility per 1000 PLHIV.

BackgroundEvidence for the effectiveness of continuous quality improvement (CQI) in resource-poor settings is very limited. We aimed to establish the effects of CQI on quality of antenatal HIV care in primary care clinics in rural South Africa.Methods and findingsWe conducted a stepped-wedge cluster-randomised controlled trial (RCT) comparing CQI to usual standard of antenatal care (ANC) in 7 nurse-led, public-sector primary care clinics-combined into 6 clusters-over 8 steps and 19 months. Clusters randomly switched from comparator to intervention on pre-specified dates until all had rolled over to the CQI intervention. Investigators and clusters were blinded to randomisation until 2 weeks prior to each step. The intervention was delivered by trained CQI mentors and included standard CQI tools (process maps, fishbone diagrams, run charts, Plan-Do-Study-Act [PDSA] cycles, and action learning sessions). CQI mentors worked with health workers, including nurses and HIV lay counsellors. The mentors used the standard CQI tools flexibly, tailored to local clinic needs. Health workers were the direct recipients of the intervention, whereas the ultimate beneficiaries were pregnant women attending ANC. Our 2 registered primary endpoints were viral load (VL) monitoring (which is critical for elimination of mother-to-child transmission of HIV [eMTCT] and the health of pregnant women living with HIV) and repeat HIV testing (which is necessary to identify and treat women who seroconvert during pregnancy). All pregnant women who attended their first antenatal visit at one of the 7 study clinics and were ≥18 years old at delivery were eligible for endpoint assessment. We performed intention-to-treat (ITT) analyses using modified Poisson generalised linear mixed effects models. We estimated effect sizes with time-step fixed effects and clinic random effects (Model 1). In separate models, we added a nested random clinic-time step interaction term (Model 2) or individual random effects (Model 3). Between 15 July 2015 and 30 January 2017, 2,160 participants with 13,212 ANC visits (intervention n = 6,877, control n = 6,335) were eligible for ITT analysis. No adverse events were reported. Median age at first booking was 25 years (interquartile range [IQR] 21 to 30), and median parity was 1 (IQR 0 to 2). HIV prevalence was 47% (95% CI 42% to 53%). In Model 1, CQI significantly increased VL monitoring (relative risk [RR] 1.38, 95% CI 1.21 to 1.57, p < 0.001) but did not improve repeat HIV testing (RR 1.00, 95% CI 0.88 to 1.13, p = 0.958). These results remained essentially the same in both Model 2 and Model 3. Limitations of our study include that we did not establish impact beyond the duration of the relatively short study period of 19 months, and that transition steps may have been too short to achieve the full potential impact of the CQI intervention.ConclusionsWe found that CQI can be effective at increasing quality of primary care in rural Africa. Policy makers should consider CQI as a routine intervention to boost quality of primary care in rural African communities. Implementation research should accompany future CQI use to elucidate mechanisms of action and to identify factors supporting long-term success.Trial registrationThis trial is registered at ClinicalTrials.gov under registration number NCT02626351.

Summary: Background: Rapid population growth, urbanisation, and economic development have led to an unprecedented number of waste sites in developing countries. This challenge has become a contentious international relations issue, with an unsustainable amount of waste and its health consequences often being borne by developing countries. However, little national-level evidence is available in sub-Saharan Africa to quantify the association between exposure to waste sites and health. Methods: We used panel data from the South African National Income Dynamics Study (SA-NIDS) to investigate the association between exposure to waste sites and asthma, tuberculosis, diabetes, and depression. The SA-NIDS is a panel survey of a nationally representative sample in South Africa, which includes data reporting the health status of 32 255 individuals between 2008 and 2015. The study exposure was distance of households, in km, to the nearest waste site, derived from waste site geospatial locations from the South Africa Waste Information System. Findings: We observed a substantial increase in exposure of households to waste sites between 2008 and 2015. The median distance between study households and waste sites decreased from 68·3 km (IQR 31·1–111·7) to 8·5 km (3·0–23·7). Residing within 5 km of a waste site was significantly associated with asthma (adjusted relative risk 1·41; 95% CI 1·20–1·64), tuberculosis (1·18; 1·02–1·36), diabetes (1·25; 1·05–1·49), and depression (1·08; 1·03–1·14). The association persisted even after controlling for multiple socioeconomic factors. Interpretation: We identified multiple adverse health outcomes in individuals living close to waste sites at a national level in South Africa, suggesting the need to reduce the number and size of waste sites to diminish harmful effects on health and wellbeing for communities living in close proximity to such sites. Funding: South African Medical Research Council, South African National Treasury, and Wellcome Trust.

BackgroundIn South Africa, within-country migration is common. Mobility affects many of the factors in the pathway for entry to or retention in care among people living with HIV. We characterized the patterns of migration (i.e., change in residency) among peripartum women from rural South Africa and their association with first-year postpartum mortality.Methods and findingsAll pregnant women aged ≥15 years were followed-up during pregnancy and the first year postpartum in a population-based longitudinal demographic and HIV surveillance program in KwaZulu-Natal, South Africa, from 2000 to 2016. During the household surveys (every 4-6 months), each household head was interviewed to record demographic components of the household, including composition, migration, and mortality. External migration was defined as moving (i.e., change in residency) into or out of the study area. For women of reproductive age, detailed information on new pregnancy and birth was recorded. Maternal death was ascertained via verbal autopsy and HIV status at delivery via annual HIV surveys. We fitted mixed-effects Cox regression models adjusting for multiple pregnancies per individual. Overall, 19,334 women had 30,291 pregnancies: 3,339 were HIV-positive, 10,958 were HIV-negative, and 15,994 had unknown HIV status at delivery. The median age was 24 (interquartile range: 20-30) years. During pregnancy and the first year postpartum, 64% (n = 19,344) and 13% (n = 3,994) did not migrate and resided within and outside the surveillance area, respectively. Of the 23% who had externally migrated at least once, 39% delivered outside the surveillance area. Overall, the mortality rate was 5.8 per 1,000 person-years (or 831 deaths per 100,000 live births) in the first year postpartum. The major causes of deaths were AIDS- or tuberculosis-related conditions both within 42 days of delivery (53%) and during the first year postpartum (62%). In this study, we observed that HIV-positive peripartum women who externally migrated and delivered outside the surveillance area had a hazard of mortality more than two times greater (hazard ratio = 2.74; 95% confidence interval 1.01-7.40, p-value = 0.047)-after adjusting for age, time period (before or after 2010), and sociodemographic status-compared to that of HIV-positive women who continuously resided within the surveillance area. Study limitations include lack of data on access to antiretroviral therapy (ART) care and social or clinical context at the destinations among mobile participants, which could lead to unmeasured confounding. Further information on how mobile postpartum women access and remain in care would be instructive.ConclusionsIn this study, we found that a substantial portion of peripartum women moved within the country around the time of delivery and experienced a significantly higher risk of mortality. Despite the scale-up of universal ART and declining trends in maternal mortality, there is an urgent need to derive a greater understanding of the mechanisms underlying this finding and to develop targeted interventions for mobile HIV-positive peripartum women.

Previously, we demonstrated that coverage of piped water in the seven years preceding a parasitological survey was strongly predictive of Schistosomiasis haematobium infection in a nested cohort of 1976 primary school children (Tanser, 2018). Here, we report on the prospective follow up of infected members of this nested cohort (N = 333) for two successive rounds following treatment. Using a negative binomial regression fitted to egg count data, we found that every percentage point increase in piped water coverage was associated with 4.4% decline in intensity of re-infection (incidence rate ratio = 0.96, 95% CI: 0.93–0.98, p=0.004) among the treated children. We therefore provide further compelling evidence in support of the scaleup of piped water as an effective control strategy against Schistosoma haematobium transmission.

Introduction: Marriage formation and dissolution are important life-course events which impact psychological well-being and health of adults and children experiencing the events. Family studies have usually concentrated on analyzing single transitions including Never Married to Married and Married to Divorced. This does not allow understanding and interrogation of dynamics of these life changing events and their effects on individuals and their families. The objective of this study was to assess determinants associated with transitions between and within marital states in South Africa.Methods: The population-based data available for this study consists of over 55, 000 subjects representing over 340, 000 person-years exposure from the Africa Health Research Institute (AHRI) in rural KwaZulu-Natal, South Africa. It was collected from 1 January 2004 to 31 December 2016. Multilevel multinomial, binary and competing risks regression models were used to model marital state occupation, transitions between marital states as well as investigate determinants of marital dissolution, respectively.Results: Between the years 2006 and 2007, a subject was more likely to be married than never married when compared to years 2004 − 2005. After 2007, subjects were less likely to be married than never married and the trend reduced over the years up to 2016 [with OR=0.86, CI=(0.78; 0.94), OR=0.71, CI=(0.64; 0.78), OR=0.60, CI=(0.54; 0.67), OR=0.50, CI=(0.44; 0.56), and OR = 0.43, CI = (0.38; 0.48)] for periods 2008 − 2009, 2010 − 2011, 2012 − 2013, 2014 − 2015, and 2016, respectively. In 2008 − 2009, subjects were more likely to experience a marital dissolution than in the period 2004 − 2005 and the trend slightly reduces from 2010 until 2013 [OR=24.49, CI=(5.53; 108.37)]. Raising age at first sexual debut was found to be inversely associated with a marital dissolution [OR = 0.97;CI = (0.95; 0.99)]. Highly educated subjects were more likely to stay in one marital state than those who never went to school [OR=6.43, CI=(4.89; 8.47), OR=18.86, CI=(1.14; 53.31), and OR=2.96, CI=(1.96; 4.46) for being married, separated and widowed, respectively, among subjects with tertiary education]. As the age at first marriage increased, subjects became less likely to experience a marital separation [OR = 0.06, CI = (0.00; 1.11), OR = 0.05, CI = (0.00; 0.91), and OR = 0.04, CI = (0.00; 0.76) for subjects who entered a first marriage at ages 18 − 22, 23 − 29, and 30 − 40, respectively].Conclusion: The study found that marrying at later ages is associated with a lower rate of marital dissolution while more educated subjects tend to stay longer in one marital state. Sexual debut at later ages was associated with a lower likelihood of experiencing a marital dissolution. There could, however, be some factors that are not accounted for in the model that may lead to heterogeneity in these dynamics in our model specification which are captured by the random effects in the model. Nonetheless, we may postulate that existing programs that encourage delay in onset of sexual activity for HIV risk reduction for example, may also have a positive impact on lowering rates of marital dissolution, thus ultimately improving psychological and physical health.

Efavirenz-based first-line regimens have been widely used for children ≥3 years of age starting antiretroviral therapy, despite possible resistance with prior exposure to non-nucleoside reverse transcriptase inhibitors for prevention of mother-to-child transmission (PMTCT). We used logistic regression to examine the association between PMTCT exposure and viral failure (VF) defined as two consecutive viral loads (VL)>1000 copies/ml between 6-18 months on ART. Children with previous nevirapine exposure for PMTCT were not at higher risk of VF compared to unexposed children (adjusted Odds Ratio (aOR): 0.79; 95% CI:0.56, 1.11).

Abstract Background Maternal mortality remains a tragedy and a key determinant for child survival. There is increasing evidence that the hazard ratio of demising for young children escalates after the death of their mothers, but few studies has been done in rural areas were HIV/AIDS is more prevalent. The aim of this study is to investigate the survival of children who lost their mothers soon or after their births in a rural setup with high HIV prevalence in South Africa. Methods This study used a data set from Africa Health Research Institute in rural South Africa.The study population comprised children (0–10 years of age) from 2000 to 2014. We employed a Cox regression modelling approach to estimate greatest temporal hazard of the child after the death of their mothers, accounting for the confounding influence of wealth index of the household and HIV status of the mother. Results We found 62,600 live births, and that 2191 children died when they were less than or equal to 10 years old. The mortality rates for

Abstract Background Large geographical variations in the intensity of the HIV epidemic in sub-Saharan Africa call for geographically targeted resource allocation where burdens are greatest. However, data available for mapping the geographic variability of HIV prevalence and detecting HIV ‘hotspots’ is scarce, and population-based surveillance data are not always available. Here, we evaluated the viability of using clinic-based HIV prevalence data to measure the spatial variability of HIV in South Africa and Tanzania. Methods Population-based and clinic-based HIV data from a small HIV hyper-endemic rural community in South Africa as well as for the country of Tanzania were used to map smoothed HIV prevalence using kernel interpolation techniques. Spatial variables were included in clinic-based models using co-kriging methods to assess whether cofactors improve clinic-based spatial HIV prevalence predictions. Clinic- and population-based smoothed prevalence maps were compared using partial rank correlation coefficients and residual local indicators of spatial autocorrelation. Results Routinely-collected clinic-based data captured most of the geographical heterogeneity described by population-based data but failed to detect some pockets of high prevalence. Analyses indicated that clinic-based data could accurately predict the spatial location of so-called HIV ‘hotspots’ in > 50% of the high HIV burden areas. Conclusion Clinic-based data can be used to accurately map the broad spatial structure of HIV prevalence and to identify most of the areas where the burden of the infection is concentrated (HIV ‘hotspots’). Where population-based data are not available, HIV data collected from health facilities may provide a second-best option to generate valid spatial prevalence estimates for geographical targeting and resource allocation.

Abstract Background Many low- and middle-income countries are facing a double burden of disease with persisting high levels of infectious disease, and an increasing prevalence of non-communicable disease (NCD). Within these settings, complex processes and transitions concerning health and population are underway, altering population dynamics and patterns of disease. Understanding the mechanisms through which changing socioeconomic and environmental contexts may influence health is central to developing appropriate public health policy. Migration, which involves a change in environment and health exposure, is one such mechanism. Methods This study uses Competing Risk Models to examine the relationship between internal migration and premature mortality from AIDS/TB and NCDs. The analysis employs 9 to 14 years of longitudinal data from four Health and Demographic Surveillance Systems (HDSS) of the INDEPTH Network located in Kenya and South Africa (populations ranging from 71 to 223 thousand). The study tests whether the mortality of migrants converges to that of non-migrants over the period of observation, controlling for age, sex and education level. Results In all four HDSS, AIDS/TB has a strong influence on overall deaths. However, in all sites the probability of premature death (45q15) due to AIDS/TB is declining in recent periods, having exceeded 0.39 in the South African sites and 0.18 in the Kenyan sites in earlier years. In general, the migration effect presents similar patterns in relation to both AIDS/TB and NCD mortality, and shows a migrant mortality disadvantage with no convergence between migrants and non-migrants over the period of observation. Return migrants to the Agincourt HDSS (South Africa) are on average four times more likely to die of AIDS/TB or NCDs than are non-migrants. In the Africa Health Research Institute (South Africa) female return migrants have approximately twice the risk of dying from AIDS/TB from the year 2004 onwards, while there is a divergence to higher AIDS/TB mortality risk amongst female migrants to the Nairobi HDSS from 2010. Conclusion Results suggest that structural socioeconomic issues, rather than epidemic dynamics are likely to be associated with differences in mortality risk by migrant status. Interventions aimed at improving recent migrant’s access to treatment may mitigate risk.

Abstract Background List randomization (LR), a survey method intended to mitigate biases related to sensitive true/false questions, has received recent attention from researchers. However, tests of its validity are limited, with no study comparing LR-elicited results with individually known truths. We conducted a test of LR for HIV-related responses in a high HIV prevalence setting in KwaZulu-Natal. By using researcher-known HIV serostatus and HIV test refusal data, we were able to assess how LR and direct questionnaires perform against individual known truth. Methods Participants were recruited from the participation list from the 2016 round of the Africa Health Research Institute demographic surveillance system, oversampling individuals who were HIV positive. Participants were randomized to two study arms. In Arm A, participants were presented five true/false statements, one of which was the sensitive item, the others non-sensitive. Participants were then asked how many of the five statements they believed were true. In Arm B, participants were asked about each statement individually. LR estimates used data from both arms, while direct estimates were generated from Arm B alone. We compared elicited responses to HIV testing and serostatus data collected through the demographic surveillance system. Results We enrolled 483 participants, 262 (54%) were randomly assigned to Arm A, and 221 (46%) to Arm B. LR estimated 56% (95% CI: 40 to 72%) of the population to be HIV-negative, compared to 47% (95% CI: 39 to 54%) using direct estimates; the population-estimate of the true value was 32% (95% CI: 28 to 36%). LR estimates yielded HIV test refusal percentages of 55% (95% CI: 37 to 73%) compared to 13% (95% CI: 8 to 17%) by direct estimation, and 15% (95% CI: 12 to 18%) based on observed past behavior. Conclusions In this context, LR performed poorly when compared to known truth, and did not improve estimates over direct questioning methods when comparing with known truth. These results may reflect difficulties in implementation or comprehension of the LR approach, which is inherently complex. Adjustments to delivery procedures may improve LR’s usefulness. Further investigation of the cognitive processes of participants in answering LR surveys is warranted.

Abstract Background In South Africa (home of the largest HIV epidemic globally), there are high levels of mobility. While studies produced in the recent past provide useful perspectives to the mobility-HIV risk linkage, systematic analyses are needed for in-depth understanding of the complex dynamics between mobility and HIV risk. We plan to undertake an evidence-based review of existing literature connecting mobility and increased risky sexual behavior as well as risk of HIV acquisition in South Africa. Methods/design We will conduct a mixed-method systematic review of peer-reviewed studies published between 2000 and 2015. In particular, we will search for relevant South African studies from the following databases: MEDLINE, EMBASE, Web of Science, and J-STOR databases. Studies explicitly examining HIV and labor migration will be eligible for inclusion, while non-empirical work and other studies on key vulnerable populations such as commercial sex workers (CSW) and men who have sex with men (MSM) will be excluded. Discussion The proposed mixed-method systematic review will employ a three-phase sequential approach [i.e., (i) identifying relevant studies through data extraction (validated by use of Distiller-SR data management software), (ii) qualitative synthesis, and (iii) quantitative synthesis including meta-analysis data]. Recurrent ideas and conclusions from syntheses will be compiled into key themes and further processed into categories and sub-themes constituting the primary and secondary outcomes of this study. Synthesis of main findings from different studies examining the subject issue here may uncover important research gaps in this literature, laying a strong foundation for research and development of sustainable localized migrant-specific HIV prevention strategies in South Africa. Systematic review registration Our protocol was registered with PROSPERO under registration number: CRD 42017055580. (https://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42017055580)

Abstract Under the premise that in a resource-constrained environment such as Sub-Saharan Africa it is not possible to do everything, to everyone, everywhere, detailed geographical knowledge about the HIV epidemic becomes essential to tailor programmatic responses to specific local needs. However, the design and evaluation of national HIV programs often rely on aggregated national level data. Against this background, here we proposed a model to produce high-resolution maps of intranational estimates of HIV prevalence in Kenya, Malawi, Mozambique and Tanzania based on spatial variables. The HIV prevalence maps generated highlight the stark spatial disparities in the epidemic within a country, and localize areas where both the burden and drivers of the HIV epidemic are concentrated. Under an era focused on optimal allocation of evidence-based interventions for populations at greatest risk in areas of greatest HIV burden, as proposed by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United States President’s Emergency Plan for AIDS Relief (PEPFAR), such maps provide essential information that strategically targets geographic areas and populations where resources can achieve the greatest impact.

Summary: Background: The roll-out of antiretroviral therapy (ART) has changed contexts of HIV risk, but the influence on HIV incidence among young women is not clear. We aimed to summarise direct estimates of HIV incidence among adolescent girls and young women since ART and before large investments in targeted prevention for those in sub-Saharan Africa. Methods: We did a systematic review and meta-analysis. We searched MEDLINE, Embase, Web of Science, Global Health, and CINAHL for studies reporting HIV incidence data from serological samples collected among females aged 15–24 years in ten countries (Kenya, Lesotho, Malawi, Mozambique, South Africa, Swaziland, Tanzania, Uganda, Zambia, and Zimbabwe) that were selected for DREAMS investment in 2015. We only included articles published in English. Our main outcome was to summarise recent levels and trends in HIV incidence estimates collected between 2005 and 2015, published or received from study authors, by age and sex, and pooled by region. Findings: 51 studies were identified from nine of the ten DREAMS countries; no eligible studies from Lesotho were identified. Directly observed HIV incidence rates were lowest among females aged 13–19 years in Kumi, Uganda (0·38 cases per 100 person-years); and directly observed HIV incidence rates were highest in KwaZulu-Natal, South Africa (7·79 per 100 person-years among females aged 15–19 years, and 8·63 in those aged 20–24 years), among fishing communities in Uganda (12·40 per 100 person-years in females aged 15–19 years and 4·70 in those aged 20–24 years), and among female sex workers aged 18–24 years in South Africa (13·20 per 100 person-years) and Zimbabwe (10·80). In pooled rates from the general population studies, the greatest sex differentials were in the youngest age groups—ie, females aged 15–19 years compared with male peers in both southern African (pooled relative risk 5·94, 95% CI 3·39–10·44) and eastern African countries (3·22, 1·51–6·87), and not significantly different among those aged 25–29 years in either region. Incidence often peaked earlier (during teenage years) among high-risk groups compared with general populations. Since 2005, HIV incidence among adolescent girls and young women declined in Rakai (Uganda) and Manicaland (Zimbabwe), and also declined among female sex workers in Kenya, but not in the highest-risk communities in South Africa and Uganda. Interpretation: Few sources of direct estimates of HIV incidence exist in high-burden countries and trend analyses with disaggregated data for age and sex are rare but indicate recent declines among adolescent girls and young women. In some of the highest-risk settings, however, little evidence exists to suggest ART availability and other efforts slowed transmission by 2016. Despite wide geographical diversity in absolute levels of incidence in adolescent girls and young women, risk relative to males persisted in all settings, with the greatest sex differentials in the youngest age groups. To end new infections among the growing population of adolescents in sub-Saharan Africa, prevention programmes must address gender inequalities driving excessive risk among adolescent girls. Funding: This work was conducted as part of a planning grant funded by the Bill & Melinda Gates Foundation.