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Background: HIV incidence among adolescent girls and young women (AGYW) remains high, with their male partners a prominent factor in sustaining these elevated rates. Partnership characteristics remain important metrics for determining HIV risk, with evidence indicating that AGYW engaged in transactional and age-disparate relationships face greater HIV exposure. This study examines the risk posed to AGYW in a relationship with a "Blesser", defined as male who provides his female partner with their material needs or desires in exchange for a sexual relationship, an age-disparate (5 or more years older) partner, and the potential compounded risk of being a relationship with a partner or partners who are considered both a "Blesser" and age-disparate., Methods: A cross -sectional household based representative sample of AGYW (aged between 12-24 years) were enrolled in the study (n = 18 926) from the districts of City of Johannesburg and Ekurhuleni in the Gauteng province and the Districts of eThekwini and uMgungundlovu in the province of KwaZulu-Natal (KZN) in South Africa between March 13, 2017 to June 22, 2018. Participants completed a structured questionnaire and provided finger-prick blood samples for laboratory measurements. Our analysis used descriptive statistics and multiple binary logistic regressions accounting for survey weights, clustering and stratification., Findings: The median age of the sample was 21 years old (Interquartile range: 19-23) and nearly three quarters (73.7%) were currently attending school. Whilst all relationships exposed AGYW to potential HIV risk, multiple binary logistic regression analysis revealed that AGYW in a relationship with both a Blesser and an age-disparate partner were more likely to be HIV positive (AOR: 3.12, 95% CI: 1.76-5.53, p < 0.001), diagnosed with an STI (AOR: 4.60, 95% CI: 2.99-7.08, p < 0.001), had 2 or more sexual partners in the previous 12 months (AOR: 6.37, 95% CI: 3.85-10.54, p < 0.001), engaged in sexual activity at age 15 or younger (AOR: 3.67, 95% CI: 2.36-5.69, p < 0.001) and more likely to have ever been pregnant (AOR: 2.60, 95% CI: 1.24-5.45, p < 0.05) than those not in a relationship with either a Blesser or age-disparate partner., Conclusion: Different relationships present different HIV risk to AGYW. AGYW who had engaged in relationships with both a Blesser and an age-disparate partner were at greater HIV risk when examined against these relationships independent of one another. The data reveals the compounded HIV risk of being in both a transactional and age-disparate relationship., (© 2022. The Author(s).)

Background: Intimate partner violence (IPV) may affect the HIV-treatment cascade., Setting: Four high HIV-prevalence DREAMS health districts in South Africa., Methods: Secondary analysis of cross-sectional data collected March 2017-June 2018, using random household sample of young (12-24 years) girls and women. Face-to-face interviews assessed IPV and HIV-status knowledge, and finger-prick blood draws assessed ART (antiretroviral therapy) uptake and viral suppression. We used logistic regression to estimate crude and adjusted effects of IPV on HIV knowledge, ART uptake, and viral suppression., Results: Of 18,230 adolescent girls and young women, 8413 (46%) reported ever having had sex, of whom 1118 (13%) were HIV positive. The 90:90:90 benchmarks were 61% knew their status, 86% had ART present in their blood sample, and 91% were virally suppressed. Among the entire sample of young women living with HIV, 65.6% were virally suppressed. Past year IPV was reported by 15%. In adjusted models, IPV trended toward increasing the odds that a young woman was aware she was living with HIV [adjusted odds ratios (aOR) = 1.40, 2.00-9.98, P = 0.067]. There was no association between IPV and reduced treatment use (aOR = 0.73, 0.41-1.29). IPV was independently associated with reduced viral suppression (aOR = 0.30, 0.13-0.66)., Conclusions: Addressing the role of IPV in undermining the treatment cascade for adolescent and young women is a critical issue for HIV programming., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: HIV is one of the greatest public health challenges in South Africa. Potential HIV vaccines and antibodies are thought to be cost-effective biomedical HIV prevention methods and are currently under investigation in phase I, II, and III trials. Consequently, current and future clinical trials need to ensure sufficient recruitment and retention. To achieve this goal, clinical trial staff need to understand the socio-demographic and behavioural characteristics of people volunteering to screen for these trials and their reasons for volunteering., Methods: We conducted a secondary analysis of participant screening data across five vaccine and monoclonal antibody trials at four sites in KwaZulu-Natal, South Africa. Our study reviewed the demographic, behavioural, motivational, and health-related data from the case report forms and screening questionnaires. Descriptive statistics, chi-squared, and one-way ANOVA tests were used to analyse participants' characteristics and motivation to participate in HIV vaccine and monoclonal antibody trials. Analyses were conducted using R version 3.5.2., Results: Screening data from 1934 participants, including 79.2% of women, were obtained across all five trials (1034 enrolled, 900 screened out/declined). Screened participants predominately self-identified as black, heterosexual, cisgender women or men, many with lower educational backgrounds (43.9% did not complete secondary/high school), and several self-reported HIV-risk behaviours among themselves and their partners. 10.8% of the screened participants were living with HIV. Avoiding HIV risk was the main motivation to participate in clinical trials, followed by altruistic reasons such as a desire to help the community or helping to find a vaccine., Discussion: The current recruitment approach of these trials attracts heterosexual participants who seek to reduce HIV risk and support their community. Hence, the data suggest the need for and potential acceptance of continued ongoing HIV prevention efforts. Current trials attract participants with lower educational levels, which may be driven by the site locations, current community mobilisation strategies and research site opening hours. The sites could consider more flexible working hours to accommodate working participants and find ways to connect participants to educational support and opportunities to upgrade education levels for the current clientele., Trial Registration: HVTN 100: A Safety and Immune Response Study of 2 Experimental HIV Vaccines, NCT02404311 . Registered on March 17, 2015. HVTN 111: Safety and Immune Response to a Clade C DNA HIV Vaccine, NCT02997969. Registered on December 16, 2016. HVTN 108: Evaluating the Safety and Immunogenicity of HIV Clade C DNA Vaccine and MF59- or AS01B-Adjuvanted Clade C Env Protein Vaccines in Various Combinations in Healthy, HIV-Uninfected Adults, NCT02915016. Registered on September 22, 2016. HVTN 702: Pivotal Phase 2b/3 ALVAC/Bivalent gp120/MF59 HIV Vaccine Prevention Safety and Efficacy Study in South Africa, NCT02968849. Registered on November 1, 2016. HVTN 703/HPTN 081: Evaluating the Safety and Efficacy of the VRC01 Antibody in Reducing Acquisition of HIV-1 Infection in Women, NCT02568215 . Registered on October 1, 2015., (© 2021. The Author(s).)

Curable sexually transmitted infections (STIs) affect millions of people across the world. Besides unacceptably high HIV rates, South Africa also has the highest burden of STIs in the world. The aim of the study was to investigate temporal changes in STI incidence rates using the data from ~ 10,000 women who enrolled in several HIV prevention trials, KwaZulu-Natal, South Africa (2002-2016). We particularly focused on the changes in distribution of the most influential factors and their population-level impacts on STI incidence rates over time. Characteristics of the women were compared across the study periods: 2002-2004, 2005-2008, 2009-2011, and 2012-2016. Besides multivariable Cox regression models, population attributable risks were calculated for the significant factors. Despite the significant progress in prevention, testing, and treatment programs, infection rates increased substantially from 13.6 to 20.0 per 100 person-year over the study period. Our findings provided a compelling evidence for single/non-cohabiting South African women to be the most vulnerable population who consistently and substantially contributed to increasing STI rates during the 15 years of study duration (PAR%: 44%-47%). We also highlighted the impact of women's lack of knowledge related to their partner, using injectable contraceptives, less parity, and baseline STI positivity which were increased substantially over time. Our findings suggest that a significant proportion of STIs could be prevented by targeting single/non-cohabiting. These results may provide guidance in developing more effective STI prevention programs by targeting women at highest risk of infections and delivering more realistic messages., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The HIV-1 epidemic in sub-Saharan Africa is heterogeneous with diverse unevenly distributed subtypes and regional differences in prevalence. Subtype-specific differences in disease progression rate and transmission efficiency have been reported, but the underlying biological mechanisms have not been fully characterized. Here, we tested the hypothesis that the subtypes prevalent in the East Africa, where adult prevalence rate is higher, have lower viral replication capacity (VRC) than their West African counterparts where adult prevalence rates are lower., Results: Gag-protease sequencing was performed on 213 and 160 antiretroviral-naïve chronically infected participants from West and East Africa respectively and bioinformatic tools were used to infer subtypes and recombination patterns. VRC of patient-derived gag-protease chimeric viruses from West (n = 178) and East (n = 114) Africa were determined using a green fluorescent protein reporter-based cell assay. Subtype and regional differences in VRC and amino acid variants impacting VRC were identified by statistical methods. CRF02&#95;AG (65%, n = 139), other recombinants (14%, n = 30) and pure subtypes (21%, n = 44) were identified in West Africa. Subtypes A1 (64%, n = 103), D (22%, n = 35), or recombinants (14%, n = 22) were identified in East Africa. Viruses from West Africa had significantly higher VRC compared to those from East Africa (p < 0.0001), with subtype-specific differences found among strains within West and East Africa (p < 0.0001). Recombination patterns showed a preference for subtypes D, G or J rather than subtype A in the p6 region of gag, with evidence that subtype-specific differences in this region impact VRC. Furthermore, the Gag A83V polymorphism was associated with reduced VRC in CRF02&#95;AG. HLA-A*23:01 (p = 0.0014) and HLA-C*07:01 (p = 0.002) were associated with lower VRC in subtype A infected individuals from East Africa., Conclusions: Although prevalent viruses from West Africa displayed higher VRC than those from East Africa consistent with the hypothesis that lower VRC is associated with higher population prevalence, the predominant CRF02&#95;AG strain in West Africa displayed higher VRC than other prevalent strains suggesting that VRC alone does not explain population prevalence. The study identified viral and host genetic determinants of virus replication capacity for HIV-1 CRF02&#95;AG and subtype A respectively, which may have relevance for vaccine strategies.

Background: Intimate Partner Violence (IPV) against women is a major public health and human rights problem worldwide. Sub-Saharan Africa (SSA) has one of the highest prevalence of IPV against women in the world. This study used meta-analysis to obtain pooled rural-urban and education attainment differences in the prevalence of IPV among ever-partnered women in SSA, and assessed whether the differences in IPV depended on the SSA region or period or women's age., Methods: We analysed IPV data on 233,585 ever-partnered women aged 15-49 years from 44 demographic and health surveys conducted between 2000 and 2018 in 29 SSA countries. Random-effects meta-analyses were used to estimate overall rural-urban residence and educational differences in IPV rates among the women in SSA. Subgroup analyses were also done to investigate the sources of heterogeneity in the overall meta-analysis findings., Results: The pooled prevalence of intimate partner violence was estimated to be 41.3% (37.4-45.2%). Regionally, the highest prevalence of IPV was in Middle Africa (49. 3%; 40.32-58.45), followed by East Africa (44.13%; 36.62-51.67), Southern Africa (39.36%; 34.23-44.49), and West Africa (34.30%; 27.38-41.22). The risks of experiencing IPV were significantly higher if the women had less than secondary education (RR = 1.12; 95% CI  1.07-1.22) compared to those with at least a secondary education. Generally, women who resided in a rural area had their risks of experiencing IPV increased (RR = 1.02; CI 0.96-1.06) compared to those who resided in urban areas, but the IPV increases were only significant in East Africa (RR = 1.13; CI 1.07-1.22)., Conclusion: In sub-Saharan Africa, intimate partner violence against women is widespread, but the levels are much higher among women with lower levels of education and residing in rural areas. Our findings have provided additional support to policies aimed at achieving SDG goals on the elimination of all forms of violence against women and girls in sub-Saharan Africa. For example, policies that advocate improved educational attainment, especially among women and communities in rural areas.

Background: The rising burden of the ongoing COVID-19 epidemic in South Africa has motivated the application of modeling strategies to predict the COVID-19 cases and deaths. Reliable and accurate short and long-term forecasts of COVID-19 cases and deaths, both at the national and provincial level, are a key aspect of the strategy to handle the COVID-19 epidemic in the country., Methods: In this paper we apply the previously validated approach of phenomenological models, fitting several non-linear growth curves (Richards, 3 and 4 parameter logistic, Weibull and Gompertz), to produce short term forecasts of COVID-19 cases and deaths at the national level as well as the provincial level. Using publicly available daily reported cumulative case and death data up until 22 June 2020, we report 5, 10, 15, 20, 25 and 30-day ahead forecasts of cumulative cases and deaths. All predictions are compared to the actual observed values in the forecasting period., Results: We observed that all models for cases provided accurate and similar short-term forecasts for a period of 5 days ahead at the national level, and that the three and four parameter logistic growth models provided more accurate forecasts than that obtained from the Richards model 10 days ahead. However, beyond 10 days all models underestimated the cumulative cases. Our forecasts across the models predict an additional 23,551-26,702 cases in 5 days and an additional 47,449-57,358 cases in 10 days. While the three parameter logistic growth model provided the most accurate forecasts of cumulative deaths within the 10 day period, the Gompertz model was able to better capture the changes in cumulative deaths beyond this period. Our forecasts across the models predict an additional 145-437 COVID-19 deaths in 5 days and an additional 243-947 deaths in 10 days., Conclusions: By comparing both the predictions of deaths and cases to the observed data in the forecasting period, we found that this modeling approach provides reliable and accurate forecasts for a maximum period of 10 days ahead.

Objective: Despite all efforts, high pregnancy rates are often reported in HIV biomedical intervention trials conducted in African countries. We therefore aimed to develop a pregnancy risk scoring algorithm for targeted recruitment and screening strategies among a cohort of women in South Africa., Methods: The study population was ~ 10,000 women who enrolled in one of the six biomedical intervention trials conducted in KwaZulu Natal, South Africa. Cox regression models were used to create a pregnancy risk scoring algorithm which was internally validated using standard statistical measures., Results: Five factors were identified as significant predictors of pregnancy incidence:<25 years old, not using injectable contraceptives, parity (<3), being single/not cohabiting and having ≥ 2 sexual partners in the past three months. Women with total scores of 21-24, 25-35 and 36+ were classified as being at "moderate", "high", "severe" risk of pregnancy. Sensitivity of the development and validation models were reasonably high (sensitivity 76% and 74% respectively)., Conclusion: Our risk scoring algorithm can identify and alert researchers to women who need additional non-routine pregnancy assessment and counselling, with statistically acceptable accuracy and robustness., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Modelling of longitudinal biomarkers and time-to-event data are important to monitor disease progression. However, these two variables are traditionally analyzed separately or time-varying Cox models are used. The former strategy fails to recognize the shared random-effects from the two processes while the latter assumes that longitudinal biomarkers are exogenous covariates, resulting in inefficient or biased estimates for the time-to-event model. Therefore, we used joint modelling for longitudinal and time-to-event data to assess the effect of longitudinal CD4 count on mortality., Methods: We studied 4014 patients from the Centre for the AIDS Programme of Research in South Africa (CAPRISA) who initiated ART between June 2004 and August 2013. We used proportional hazards regression model to assess the effect of baseline characteristics (excluding CD4 count) on mortality, and linear mixed effect models to evaluate the effect of baseline characteristics on the CD4 count evolution over time. Thereafter, the two analytical approaches were amalgamated to form an advanced joint model for studying the effect of longitudinal CD4 count on mortality. To illustrate the virtues of the joint model, the results from the joint model were compared to those from the time-varying Cox model., Results: Using joint modelling, we found that lower CD4 count over time was associated with a 1.3-fold increase in the risk of death, (HR: 1.34, 95% CI: 1.27-1.42). Whereas, results from the time-varying Cox model showed lower CD4 count over time was associated with a 1.2-fold increase in the risk of death, (HR: 1.17, 95% CI: 1.12-1.23)., Conclusions: Joint modelling enabled the assessment of the effect of longitudinal CD4 count on mortality while correcting for shared random effects between longitudinal and time-to-event models. In the era of universal test and treat, the evaluation of CD4 count is still crucial for guiding the initiation and discontinuation of opportunistic infections prophylaxis and assessment of late presenting patients. CD4 count can also be used when immunological failure is suspected as we have shown that it is associated with mortality.

This study was aimed at determining if the myocardial performance index (MPI) is altered in well-controlled gestational diabetics and if so whether it is predictive of adverse perinatal outcome. In a prospective cross-sectional study, 54 consecutive women with well-controlled gestational diabetes controlled on insulin or metformin in the third trimester were recruited and matched with 54 women with normal pregnancies (control group). Using Doppler echocardiography, the MPI was calculated. Sonographic biophysical and placental resistance Doppler markers in both groups were also determined. An abnormal outcome was defined as any of the following: stillbirth; neonatal death; neonatal intensive care admissions; tachypnea with pulmonary edema; neonatal cord pH < 7.15; 5-min Apgar score < 7, polycythemia; and nucleated red blood cells > 10/100 white blood cell counts, hypoglycemia. The MPI was significantly higher in the diabetic group compared to controls (p < 0.0001). Rate of adverse outcome was 22% in the diabetic group. The diabetic group with adverse outcomes had significantly elevated MPI values compared to the diabetic group with normal outcomes. There were 26 diabetics controlled on metformin and 28 controlled on insulin. The adverse outcome rate was slightly higher in the IDDM group compared to the non-insulin-dependent group but was not statistically significant. The main adverse outcomes were low Apgars (18%), hypoglycemia (22%), polycythemia (13%) and low pH in 7%. All control births had normal outcomes. MPI served as an independent predictor of adverse outcome. The MPI z-score had a good diagnostic accuracy as evidenced by the area under the ROC curve of 0.83. An MPI z-score exceeding 4.55 conferred a 90% sensitivity and 74% specificity, with 77% of outcomes correctly classified with a likelihood ratio of 3.5. The MPI is impaired in fetuses in well-controlled gestational diabetes, with fetuses with an adverse outcome having significantly higher MPI values compared to the fetuses with normal outcome in the diabetic group. MPI has the potential to improve fetal surveillance in gestational diabetes.

Objective: We identified the geographical clustering of HIV as well as those at highest risk of infection using a decade long data (2002-2012) from KwaZulu-Natal, South Africa., Methods: A total of 5,776 women who enrolled in several HIV prevention trials were included in the study. Geo-coded individual-level data were linked to the community-level characteristics using the South African Census. High-risk women were identified using a risk scoring algorithm. Generalized additive models were used to identify the significant geographical clustering of high-risk women and HIV., Results: Overall, 60% of the women were classified as high risk of HIV. HIV infection rates were estimated as high as 10 to 15 per 100 person year. Areas with high rates of HIV infections were spatially clustered and overlapped particularly in the Northern part of Durban., Conclusion: Targeting multifactorial and complex nature of the epidemic is urgently needed to identify the "high transmission" areas., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Women enrolled in human immunodeficiency virus (HIV) prevention efficacy trials receive counseling on prevention of HIV, sexually transmitted infections (STIs), and pregnancy during every visit. Incident pregnancy has an impact on efficacy outcomes. Incidence rates of pregnancy and HIV/STIs among women who became pregnant and associated risk factors were assessed., Methods: Data from 9165 women participating in HIV prevention trials in KwaZulu-Natal, South Africa from 2002-2012 were combined. Demographic and behavioral predictors of incidence pregnancy and incidence HIV and STIs were determined using Cox regression models., Results: Overall pregnancy incidence was 9.6 per 100 person-year (py) (95% confidence interval [Cl], 9.1-10.3). Human immunodeficiency virus incidence among pregnant women was 5.93 per 100 py (95% Cl, 4.73-7.44). Incidence of STIs among pregnant women for Chlamydia trachomatis, Trichomonas vaginalis, Neisseria gonorrhoeae, and Treponema pallidum (syphilis) were 10.87, 7.42, 3.92, and 1.43 per 100 py, respectively. In the adjusted analyses, we observed overlapping risk factors for HIV acquisition during pregnancy, ie, young age, not married/not cohabitating, and low parity. The risk of pregnancy and HIV acquisition is more than 3 times higher among young women (<20 years of age)., Conclusions: We identified overlapping risk factors for pregnancy and HIV incidence, suggesting an urgent need for appropriate, targeted, individual-centred counseling for women participating in HIV prevention trials.

Background: Carotid cavernous fistulas (CCFs) are relatively uncommon and are difficult to diagnose clinically. Radiological imaging plays a significant role in making the diagnosis with recent advances improving the ability of radiologists to diagnose the condition. Despite these developments, digital subtracted angiography (DSA) remains the gold standard in diagnosing CCFs and simultaneously provides the opportunity for intervention., Objectives: To determine the imaging findings of patients presenting to Inkosi Albert Luthuli Central Hospital (IALCH) with a CCF and to assess the outcome of endovascular intervention., Method: We reviewed the electronic records and archived imaging data of consecutive patients diagnosed with CCF between January 2003 and May 2016 at IALCH, in particular, the imaging findings, intervention and subsequent outcomes., Results: Computed tomography (CT) was the most utilised imaging modality prior to patients undergoing DSA. A dilated superior ophthalmic vein (96%) was the most prevalent imaging finding on axial imaging. At DSA, all except two patients had high-flow fistulas. The fistulas predominantly drained anteriorly (69.44%) and a cavernous internal carotid artery aneurysm was identified in eight patients. Occlusion of the fistula was attained in all patients that were compliant with follow-up and underwent intervention ( n = 36, 100%), but parent artery sacrifice was required in 10 cases (27.78%)., Conclusion: A wide range of imaging modalities can be used in the workup of a CCF. CT is currently the most accessible modality in our setting, with limited access to magnetic resonance imaging. On axial imaging, a dilated superior ophthalmic vein is the commonest finding. Classification of a fistula according to flow dynamics and noting the presence of aneurysms or pseudoaneurysms was found to be more practical in comparison to the traditional Barrow's classification. Management outcomes at our institution compare well with available local and international data., Competing Interests: The authors declare that they have no financial or personal relationship(s) which may have inappropriately influenced them in writing this article., (© 2018. The Authors.)

Rifabutin, used to treat HIV-infected tuberculosis, shows highly variable drug exposure, complicating dosing. Effects of SLCO1B1 polymorphisms on rifabutin pharmacokinetics were investigated in 35 African HIV-infected tuberculosis patients after multiple doses. Nonlinear mixed-effects modeling found that influential covariates for the pharmacokinetics were weight, sex, and a 30% increased bioavailability among heterozygous carriers of SLCO1B1 rs1104581 (previously associated with low rifampin concentrations). Larger studies are needed to understand the complex interactions of host genetics in HIV-infected tuberculosis patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT00640887.)., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)