Understanding the impact of women's correct risk perception on human immunodeficiency virus diagnosis: Insights from South Africa.

BACKGROUND: South African women have the highest burden of HIV infections globally. We investigated the temporal trends and the impact of key factors associated with HIV diagnosis among a nationally representative cohort of South African women. METHODS: Total of 24,657 women who participated in the National HIV, Behaviour and Health Surveys conducted from 2002-to-2017. RESULTS: Despite decades-long prevention efforts, we observed a significant increase in HIV prevalence over time (22% in 2002 to 21% in 2005-2008 and 29% in 2012-2017). Overall, 46% of the women living with HIV were not aware of their risk of HIV with age-specific disparities. Our findings revealed compelling evidence between HIV seropositivity and high HIV risk-perception (adjusted Odds Ratio (aOR):1.47 to 3.29) which increased overtime and exceeded the other factors. At a population-level, 45% of the HIV diagnoses were exclusively associated with women who believed they were at risk of HIV in 2012-2017. Women who reported using condoms at last sexual act were also at increased risk of HIV infection, with a population attributable risk of 18% (2002) to 21% (2012-2017). CONCLUSION: There is an urgent need for culturally, socially, and linguistically appropriate prevention and awareness campaigns with realistic, non-confrontational messages.

Preventing Stunting in South African Children Under 5: Evaluating the Combined Impacts of Maternal Characteristics and Low Socioeconomic Conditions.

More than 140 million children under five suffered from stunting in 2020. This highlights the ongoing challenge of addressing childhood malnutrition globally. We utilized data from a nationally representative sample of children under five years of age (n = 14,151) who participated in five cycles of the South African National Income Dynamics Study (SA-NIDS) (2008-2017). We estimated the proportion of stunted children attributed to the mothers' anthropometric characteristics and socioeconomic conditions. We also quantified the population-level burden of low-socioeconomic conditions on hunger/food insecurity among pregnant women (n = 22,814) who participated in the nine rounds of the South African General Household Surveys (GHS) (2008-2021). Results from weighted-multivariate logistic regression were incorporated into the population-level impacts of correlates of stunting and low-socioeconomic conditions. The prevalence of stunting declined from 25% in 2008 to 23% in 2017. Mothers' anthropometric measures (underweight/height < 160 cm), marital status, low education, absence of medical insurance and low-socioeconomic conditions were all identified as the most influential risk factors for stunting. Their population-level impacts on stunting increased substantially from 34% (in 2008) to 65% (in 2017). Comprehensive strategies emphasizing enhanced food security, extended breastfeeding, appropriate nutrition, and access to adequate healthcare and education are urgently needed to reduce the burden of food insecurity low-socioeconomic, malnutrition, and its long-term consequences.

Quantifying impact of obesity on cardiometabolic comorbidities and public health implications: Insights from South Africa.

INTRODUCTION: South Africa has the highest obesity and hypertension rates in the African region. In this cross-sectional study, we aimed to quantify the correlates and burden of obesity and their impacts on cardiometabolic conditions. METHODS: The study population was 80,270 men(41 %) and women(59 %) who participated in South African national surveys (2008-to-2017). Weighted-logistic regression models and the population attributable risk (PAR %) were used after accounting for the correlation structure of the risk factors in a multifactorial setting. RESULTS: Overall, 63 % of the women and 28 % of the men were either overweight or obese. Parity was identified as the most influential factor and exclusively associated with 62 % of the obesity in women; being married/cohabiting had the highest impact on obesity in men and associated with 37 % of the obesity. Overall, 69 % of them had comorbidities including hypertension, diabetes and heart disease. More than 40 % of the comorbidities were attributed to overweight/obesity. CONCLUSION: Developing culturally appropriate prevention programs are urgently needed to raise awareness of obesity, hypertension and their impacts on severe cardiometabolic diseases. This approach would also significantly reduce COVID-19 related poor health outcomes and premature deaths.

Geospatial variations in socioeconomic conditions and health outcomes in COVID-19 era: insights from South Africa (2020-2022).

South Africa also has the highest burden of coronavirus disease 2019 (COVID-19) related comorbidities in Africa. We aimed to quantify the temporal and geospatial changes in unemployment, food insecurity, and their combined impact on depressive symptoms among South Africans who participated into several rounds of national surveys. We estimated the population-attributable risk percent (PAR%) for the combinations of the risk factors after accounting for their correlation structure in multifactorial setting. Our study provided compelling evidence for immediate and severe effect of the pandemic where 60% of South Africans reported household food insecurity or household hunger, shortly after the pandemic emerged in 2020. Despite the grants provided by the government, these factors were also identified as the most influential risk factors (adjusted odds ratios (aORs) ranged from 2.06 to 3.10, p < 0.001) for depressive symptoms and collectively associated with 62% and 53% of the mental health symptoms in men and women, respectively. Similar pattern was observed among pregnant women and 41% of the depressive symptoms were exclusively associated with those who reported household hunger. However, aORs associated with the concerns around pandemic and vaccine were mostly not significant and ranged from 1.12 to 1.26 which resulted substantially lower impacts on depressive symptoms (PAR%:7%-and-14%). Our findings suggest that South Africa still has unacceptably high rates of hunger which is accelerated during the pandemic. These results may have significant clinical and epidemiological implications and may also bring partial explanation for the low vaccine coverage in the country, as priorities and concerns are skewed towards economic concerns and food insecurity.

Quantifying the temporal changes in geographical-level contributions of risk factors to hypertension (2008-2017): Results from national surveys.

South Africa has one of the world's highest proportions of hypertensive individuals, which has become a major public health problem. Understanding the temporal and spatial patterns in hypertension rates is crucial for evaluating the existing prevention and care models, which have not been fully understood in South Africa. The geoadditive models were used to quantify the geographical clustering of hypertension in the Black South African population enrolled in the most recent cross-sectional national surveys (2008-2017). Population-attributable risks were calculated for modifiable risk factors. 80,270 men (41%) and women (59%) aged 15+ were included. Using the 2017 guidelines, 52% of the men and 51% of the women were classified as hypertensive. As expected, these proportions were slightly lower when we used the previous guidelines (48% and 47% for men and women, respectively). There was significant geospatial heterogeneity in hypertension prevalence with substantial province-specific disparities. Western, Northern, and Eastern Capes were the most significant provinces, with >50% of the hypertensive men and women. The population-level impact of obesity remained high in all provinces, where 33%-to-57% and 47%-to-65% of hypertensives were exclusively associated with obese/overweight men and women respectively. Despite some improvements in certain areas, most of the country is behind the targeted levels set in 2011/2013. Identifying the most relevant risk factors and their sub-geographical-level contributions to hypertension may have significant public health implications for developing and implementing cost-effective prevention programs to raise awareness of healthy diet and lifestyle behaviours.

Developing and Validating Risk Algorithm for Hypertension in South Africa: Results from a Nationally Representative Cohort (2008-2017).

INTRODUCTION: There is compelling evidence of significant country-level disparities where African countries, particularly South Africa, have the highest hypertension rates in the world. AIM: To develop and validate a simple risk scoring algorithm for hypertension in a large cohort (80,270) of South African men and women. METHODS: Multivariable logistic regression models were used to build our hypertension risk scoring algorithm and validated externally and internally using the standard statistical techniques. We also compared our risk scores with the results from the Framingham risk prediction model for hypertension. RESULTS: Six factors were identified as the significant correlates of hypertension: age, education, obesity, smoking, alcohol intake and exercise. A score of ≥ 25 (out of 57) for men and ≥ 35 (out of 75) for women were selected as the optimum cut-points with 82% (43%) and 83% (49%) sensitivity (specificity) for males and females, respectively in the development datasets. We estimated probabilities of developing hypertension using the Framingham risk prediction model, which were higher among those with higher scores for hypertension. CONCLUSIONS: Identifying, targeting and prioritising individuals at highest risk of hypertension will have significant impact on preventing severe cardiometabolic diseases by scaling up healthy diet and life-style factors. Our six-item risk scoring algorithm may be included as part of hypertension prevention and treatment programs by targeting older individuals with high body fat measurements who are at highest risk of developing hypertension.

Strategies implemented for accurate dispensing of an investigational new drug in a multi-site HIV prevention clinical trial.

Safe practices for dispensing investigational product (IP) during clinical trials are not standardized and information in this regard is often limited. ASPIRE was a Phase 3 safety and effectiveness trial of a vaginal matrix ring containing 25 mg of dapivirine for the prevention of HIV-1 in women. The study enrolled 2629 women at 15 clinical research sites in Malawi, Uganda, South Africa and Zimbabwe who were randomized in a 1:1 ratio to receive either a vaginal ring containing 25 mg of dapivirine or a matching placebo vaginal ring. The vaginal rings and packaging were identical in appearance in order to maintain the study blind. A real-time, documented second check of the dispensing process was conducted by a second pharmacy staff. Frequent inventory counts and real time accountability audits were also useful for rapidly identifying a dispensing error. A total of 52,625 vaginal rings were dispensed with only three documented pharmacy dispensing errors. There were zero dispensing errors at 13 of the 15 sites with an overall rate of <1.0 per 10,000 rings dispensed. Our study findings support the implementation of a double check dispensing process and real time accountability audits as standard practice in clinical trials.

Impact of recurrent sexually transmitted infections on HIV seroconversion: Results from multi-state frailty models.

After several decades of research, South Africa is still considered to be the epicentre of HIV epidemic. The country also has the highest burden of sexually transmitted infections (STIs) which have been frequently linked to increasing rates of HIV transmission due to biological and behavioural associations between these two pathogeneses. We investigated the cumulative impact of recurrent STIs on subsequent HIV seroconversion among a cohort of South African women. We used the 'frailty' models which can account for the heterogeneity due to the recurrent STIs in a longitudinal setting. The lowest HIV incidence rate was 5.0/100 person-year among women who had no baseline STI and remained negative during the follow-up. This estimate was three times higher among those who had recurrent STIs in the follow-up period regardless of their STI status at baseline (15.8 and 14.0/100 person-year for women with and without STI diagnosis at baseline, respectively). Besides younger age and certain partnership characteristics, our data provided compelling evidence for the impact of recurrent STI. diagnoses on increasing rates of HIV. At the population-level, 65% of HIV infections collectively associated with recurrent STIs. These results have significant clinical and epidemiological implications and may play critical role in the trajectory of the infections in the region.

The Impact of Male Partner Circumcision on Women's Health Outcomes.

Medical male circumcision is a proven method of HIV risk reduction in men with no known direct benefit to women. We investigated the benefit of partner circumcision on women's health. We conducted a secondary analysis of 5,029 women enrolled in the Vaginal and Oral Interventions to Control the Epidemic trial across 15 African sites, to look at the impact of partner circumcision status on sexually transmitted infections, pregnancy, frequency of sex, and condom use in women. Of 4,982 participants with a baseline response, 31% had circumcised partners. Women with circumcised partners had a significantly reduced risk of syphilis acquisition, hazard ratio 0.51 (0.26, 1.00), p value = .05. Participants with uncircumcised partners were significantly less likely to have used a condom at the last sex act than the other two groups, adj. relative risk 0.86 (0.80, 0.92), adj. p value < .0001. We found no evidence of sexual risk compensation in women with circumcised partners.

Social harms in female-initiated HIV prevention method research: state of the evidence.

OBJECTIVES: Assessment of safety is an integral part of real-time monitoring in clinical trials. In HIV prevention research, safety of investigational products and trial participation has been expanded to include monitoring for 'social harms', generally defined as negative consequences of trial participation that may manifest in social, psychological, or physical ways. Further research on social harms within HIV prevention research is needed to understand the potential safety risks for women and advance the implementation of prevention methods in real-world contexts. METHODS: Secondary analysis of quantitative data from three randomized, double-blind, placebo-controlled trials of microbicide candidates in sub-Saharan Africa was conducted. Additionally, we assessed data from two prospective cohort studies that included participants who became HIV-positive or pregnant during parent trials. RESULTS: Social harms reporting was low across the largest and most recent microbicide studies. Social harm incidence per 100 person-years ranged from 1.10 (95% CI 0.78-1.52) to 3.25 (95% CI 2.83-3.74) in the phased trials. Reporting differed by dosing mechanism (e.g. vaginal gel, oral tablet, ring) and study, most likely as a function of measurement differences. Social harms were most frequently associated with male partners, rather than, for example, experiences of stigma in the community. CONCLUSION: Measurement and screening for social harms is an important component of conducting ethical research of novel HIV prevention methods. To date, social harm incidence reported in microbicide trials has been relatively low (<4% per 100 person-years), and the majority have been partner-related events. However, any incidence of social harm within the context of HIV prevention is important to capture and understand for the safety of individuals, and for the successful impact of prevention methods in a real-world context.

Sharing of Investigational Drug Among Participants in the Voice Trial.

Product sharing among participants can impact on adherence and compromise the outcome in clinical trials. We describe incidents of product sharing at the Durban clinical research sites conducting the VOICE trial. The Durban sites enrolled 2750 women with 1103 and 1647 participants randomized to the vaginal gel and oral tablet arms respectively. Monthly pill and applicator counts including product assessments were conducted by pharmacists. Discrepancies with product counts prompted discussions with participants. Thirty-two cases of product sharing were identified. Vaginal gels were more commonly shared than oral tablets. Product sharing between study participants and their female friends or relatives living in the same household was identified as the most common source of product sharing in this analysis. Study product counts and pharmacist-driven discussions with participants may help to identify reasons for product sharing and inform the development of strategies for PrEP implementation outside of the research setting. ClinicalTrials.gov number: NCT00705679.

Contraception use and impact on pregnancy prevention in women participating in an HIV prevention trial in South Africa.

BACKGROUND: Unplanned pregnancy rates in South Africa are high. Effective use of contraception is therefore an essential public health intervention to prevent unplanned pregnancies. This study describes contraception use and its impact on pregnancy in women participating in HIV prevention research and its implications for public health practice. METHOD: A secondary analysis of sociodemographic, behavioural, contraception use, and pregnancy incidence data was conducted amongst women participating in the Microbicides Development Programme (MDP) 301 trial conducted in Durban, South Africa. Log-rank tests were carried out to compare the pregnancy incidence between women who reported use of injectable contraceptive methods compared to women using oral contraceptive pills, using condoms and other methods (intrauterine device, traditional methods and natural methods). The effect of types of contraceptives on pregnancy incidence was assessed using Cox proportional hazards regression models. RESULTS: Of the 2018 women enrolled, injectable contraception was the most commonly used method (52%) compared to pills, condoms for pregnancy prevention and other methods. Injectable contraception use was associated with lower crude pregnancy incidence of 4.4 per 100 woman-years [95% confidence interval (95% CI 3.3-5.9)] compared to women using pills [19.3 per 100 woman-years (95% CI 13.3-28.0)], condoms [19.7 per 100 woman-years (95% CI 16.3-23.6)] and other methods [11.5 per 100 woman-years (95% CI 7.5-17.6)]. This effect remained significant when adjusted for age, level of education, condom use at last sex act [hazard ratio 0.27, (95% CI 0.16-0.47, p<0.001)]. CONCLUSION: Injectable contraception offered a high level of protection against pregnancies among women in Durban. TRIAL REGISTRATION NUMBER: ISRCTN64716212.

Ethical Considerations in Implementing a Biometric Co-Enrolment Prevention System in Clinical Trials in South Africa

Preventing co-enrolment in clinical trials ensures participant safety and data integrity. To facilitate co-enrolment checks; a novel biometric coenrolment prevention system (BCEPS) was developed and implemented in 2010 by the HIV Prevention Research Unit (HPRU) in collaboration with the South African Medical Research Council's (SAMRC) Information Technology Services Division. The use of this web-based system to capture participant's identification details in real time was approved by the SAMRC Ethics Committee. BCEPS was implemented at 13 other research organisations conducting clinical trials in South Africa (SA). Participants who screened at the clinical research sites (CRSs) had their names; SA identity or passport number and fingerprints captured onto BCEPS after comprehensive education and discussion. This information was verified at all study visits. If a participant attempted to screen or co-enrol at multiple CRSs; the system flagged this as a potential coenrolment By addressing the ethical concerns around participant consent and rights; participant confidentiality and privacy; data security and access; and data management and storage; we were able to successfully implement BCEPS within the clinical trials conducted at HPRU; while adhering to the principles of good clinical practice (GCP); including respect for persons; beneficence and justice