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Background HIV has become a manageable chronic condition due to the success and scale-up of antiretroviral therapy (ART). Globally, South Africa has the highest number of people living with HIV (PLHIV) and research evidence indicates that countries with the highest burden of PLHIV have a substantial burden of obesity, hypertension (HPT) and type 2 diabetes (T2D). We sought to summarize the burden of these three common NCDs among PLHIV in South Africa. Methods In this systematic review, multiple databases were searched for articles reporting on the prevalence of obesity, HPT, and T2D among PLHIV in South Africa published since journal inception until March 2022. A meta-analysis was conducted using random-effects models to obtain pooled prevalence estimates of the three NCDs. Heterogeneity was assessed using X 2 test on Cochran’s Q statistic. Results We included 32 studies, with 19, 22 and 18 studies reporting the prevalence of obesity, HPT, and T2D among PLHIV, respectively. The overall prevalence of obesity, HPT, and T2D was 23.2% [95% CI 17.6; 29.9], 25.5% [95% CI 15.6; 38.7], and 6.1% [95% CI 3.8; 9.7] respectively. The prevalence of obesity was significantly higher among women ( P  = 0.034) compared to men, however the prevalence of HPT and T2D did not differ by sex. The prevalence of each of the three NCDs did not differ significantly between rural, urban, and peri-urban areas. The prevalence of obesity and T2D was higher in studies conducted between 2013 and 2022 compared to studies conducted between 2000 and 2012, while the prevalence of HPT was higher between 2000 and 2012 compared to between 2013 and 2022. Conclusions These findings suggest that South Africa is experiencing a syndemic of NCDs among people PLHIV highlighting the need to increase cost-effective interventions and management strategies that involve integrated HIV and NCD care in the South African setting.

Hypertension is a growing burden in rapidly urbanizing settings, yet longitudinal studies on its incidence and risk factors in urban populations living in resource‐constrained settings in Africa are limited. This study aimed to determine the incidence of hypertension and associated risk factors in urban middle‐aged South African men and women. Longitudinal data from the Middle‐Aged Soweto Cohort were collected at four time points between 2011 and 2025 and included: blood pressure, sociodemographic, anthropometry, chronic disease status, and medication use. Participants were included if they had complete data for at least two time points and were normotensive at baseline. The incidence of hypertension was estimated using survival analysis and the significant risk factors were determined using Cox proportional hazard models. Of the 679 eligible participants, there were 332 incident hypertension cases, and an overall incidence of 6.4 cases per 100 person years, with no significant difference between men and women (p = 0.0977). In multivariable analyses in the whole cohort, older age (hazard ratio [HR]: 1.15, 95% CI: 1.04–1.28) and higher BMI (HR: 1.22, 95% CI: 1.11–1.35) were associated with a higher risk of incident hypertension. In sex stratified analysis, higher BMI (p < 0.001) and alcohol consumption (p < 0.001) were associated with incident hypertension in men, while higher BMI (p = 0.002) and older age (p = 0.025) were associated with incident hypertension in women. The study identifies modifiable risk factors associated with incident hypertension in urban South African men and women. Sex‐specific interventions targeting ageing adults may be beneficial in resource constrained urban settings. Clinical Trial Registration: This study is not a clinical trial and does not require registration.

We investigated gluteal (GSAT) and abdominal subcutaneous adipose tissue (ASAT) DNA methylation of FKBP5 in response to a 12-week intervention in African women with obesity, as well as the effect of the rs1360780 single nucleotide polymorphism (SNP) on FKBP5 methylation, gene expression and post-exercise training adaptations in obesity and metabolic related parameters. Exercise (n = 19) participants underwent 12-weeks of supervised aerobic and resistance training while controls (n = 12) continued their usual behaviours. FKBP5 methylation was measured in GSAT and ASAT using pyrosequencing. SNP and gene expression analyses were conducted using quantitative real-time PCR. Exercise training induced FKBP5 hypermethylation at two CpG dinucleotides within intron 7. When stratified based on the rs1360780 SNP, participants with the CT genotype displayed FKBP5 hypermethylation in GSAT ( p  < 0.05), and ASAT displayed in both CC and CT carriers. CC allele carriers displayed improved cardiorespiratory fitness, insulin sensitivity, gynoid fat mass, and waist circumference ( p  < 0.05) in response to exercise training, and these parameters were attenuated in women with the CT genotype. These findings provide a basis for future studies in larger cohorts, which should assess whether FKBP5 methylation and/or genetic variants such as the rs1360780 SNP could have a significant impact on responsiveness to exercise interventions.

Introduction Dolutegravir-based antiretroviral therapy (ART), a key component of HIV treatment in low- and middle-income countries, has been associated with weight gain and increased adiposity in people living with HIV (PLWH). This weight gain, along with fat redistribution, can elevate the risk of diabetes, hypertension, and cardiovascular disease. The South African Diabetes Prevention Program (SA-DPP) is a culturally tailored lifestyle intervention addressing nutrition, physical activity, and other risky behaviors, developed for resource-limited communities. We sought to evaluate the clinical experiences of PLWH and the acceptability and suitability of the SA-DPP intervention for this population. Methods A qualitative study was conducted with PLWH and health staff from three primary health clinics in Cape Town ( n  = 35), selected through purposive sampling. The research included five focus groups and two individual interviews with PLWH, as well as five interviews (with healthcare staff (doctors, nurses (paired interview), and lay counselors; n  = 6,). The discussions explored experiences regarding HIV treatment, lifestyle challenges, education, and support from clinics, and collected perspectives on the SA-DPP materials. All sessions were transcribed and thematically analyzed for insights into feasibility and acceptability. Results The SA-DPP curriculum was well received by both PLWH and healthcare staff, who found the content and structure comprehensive and relevant to nutrition and exercise needs. Participants valued the practicality of the booklets, with experts noting that the information and suggested activities were accessible in terms of cost and availability. Both groups indicated the material supported healthy behavior changes, though some experts suggested further adaptation to address unique challenges faced by PLWH, such as stigma and cultural perceptions of body image. Conclusion The SA-DPP intervention was considered acceptable and relevant for addressing key lifestyle issues among PLWH. It has potential as a resource for managing various lifestyle-related diseases in this population, though further adaptation may be needed to enhance its relevance and address specific barriers in the context of HIV care.

Dolutegravir (DTG)-based antiretroviral therapy is the World Health Organization's preferred first-line regimen for all persons with HIV, including pregnant women. While DTG has been implicated as an obesogen associated with greater weight gain compared to other antiretrovirals, there is a paucity of data in pregnant women and their children. The Obesogenic oRigins of maternal and Child metabolic health Involving Dolutegravir (ORCHID) study is investigating associations between DTG, weight gain, and metabolic outcomes in the context of HIV. ORCHID is a prospective observational study taking place in Cape Town, South Africa (NCT04991402). A total of 1920 pregnant women with and without HIV infection are being followed from ≤18 weeks gestational age to 24 months postpartum with their children. Participants attend eleven study visits: 3 antenatal, delivery, and 7 postnatal visits. Several embedded sub-studies address specific scientific aims. Primary outcome measurements in mothers include anthropometry, blood pressure, body composition, dysglycemia, insulin resistance (IR), and dyslipidemia. Other maternal measures include demographics, resting energy expenditure, viral load, physical activity, dietary intake, hepatic steatosis, and repository specimens. Sub-study measurements include markers of adipose inflammation, gut integrity, and satiety/hunger, subcutaneous adipose tissue morphology and mitochondrial function, and metabolomics. Primary outcome measurements in children include anthropometry, adipose tissue mass, dysglycemia, IR, and dyslipidemia. Other variables include fetal growth, birth outcomes, medical/breastfeeding history, caloric intake, neurodevelopment, and repository specimens. Sub-study measurements include metabolites/lipid subspecies in umbilical cord blood, as well as breast milk composition and DTG exposure. ORCHID will play a pivotal role in defining obesogenic mechanisms and clinical consequences of DTG use in pregnancy in women with HIV and their children. It will provide insights into metabolic disease risk reduction in the context of HIV/DTG, identify intervention targets, and inform public health approaches to diminish chronic metabolic co-morbidities for women and children.

Despite its commercial availability, its high fibre, vitamin C and polyphenol content, there are limited scientific studies exploring the cardiometabolic effects of Baobab fruit powder (BFP) in humans. Due to its high fibre content, BFP may offer a potential intervention to reduce intestinal barrier dysfunction and therefore mitigate cardiometabolic risk. A randomized, double-blind, placebo-controlled trial will be conducted with 50 apparently healthy participants living with obesity. Participants will consume either 16 g of BFP or an isocaloric placebo daily for 45 days. The primary outcome will be intestinal permeability determined using the urinary lactulose/mannitol test. Secondary outcomes include blood biomarkers in intestinal permeability (lipopolysaccharide (LPS), intestinal fatty acid binding protein (IFABP), soluble cluster of differentiation 14 (sCD14) and LPS-binding protein (LBP)), microbiota diversity and composition and cardiometabolic risk markers including glucose levels, blood lipid profiles and blood pressure. Liver and kidney function will be monitored at baseline, after 2 weeks and following 45 days of consumption as safety outcomes. The study protocol ensures rigorous, weekly monitoring of participant compliance and tolerability, along with careful tracking of potential adverse events. Intention-to-treat analysis and mixed effects models will be employed for statistical analyses. Potential selection bias and participant dropout are addressed through thorough recruitment strategies and predefined sample size calculations. This research will contribute to the growing body of knowledge on dietary interventions in the context of cardiometabolic risk, particularly in populations at risk for developing metabolic disease. South African Clinical Trial Registry - SANCTR, DOH-27-062024-8061; Pan African Clinical Trial Registry – PACTR202308727853680

Background Human Immunodeficiency Virus (HIV) and type 2 diabetes (T2D) are amongst the leading causes of death in South Africa. The preferred first-line anti-retroviral treatment contains dolutegravir (DTG), shown to increase body weight, may compound the already high rates of obesity and associated risk for T2D. South Africa has widespread food insecurity, making traditional dietary strategies difficult to implement. Time-restricted eating (TRE) may be an appropriate intervention in resource-limited communities. Methods This article outlines the development and feasibility testing of a TRE intervention to inform the design of a TRE randomised controlled trial in women (20–45 years old) living with overweight/obesity and HIV, receiving DTG-based treatment from a resource-limited community in Cape Town, South Africa. Factors influencing TRE adoption were identified using the Capability, Opportunity, Motivation – Behaviour model and the Theoretical Domains Framework, combining in-depth interviews (IDIs) and focus group discussions. Participants from the IDIs went on to participate in a single arm 4-week TRE pilot trial where feasibility was explored in terms of reach, acceptability, applicability, and implementation integrity. An iterative, thematic analysis approach was employed to analyse the qualitative data. Results Participants included 33 isiXhosa -speaking women (mean age 37.1 years, mean BMI 35.9 kg/m 2 ). Thematic analysis identified psychological capability (knowledge of fasting), social influences (cultural preferences, family support), and reflective motivation (awareness of weight, health impact, motivation for TRE) as key factors influencing adoption of TRE for weight management. In a 4-week TRE pilot trial ( n  = 12), retention was 100%. Positive outcomes perceived included improved energy, appetite control and weight loss. TRE was perceived as acceptable, easy, and enjoyable. Family support facilitated adherence, while habitual and social eating and drinking practices were barriers. Compliance was high, aided by self-selected eating times, reminders, and weekly calls. Recommendations included the incorporation of dietary education sessions and text messages to provide additional support and reminders. Conclusions This study indicates that TRE is a feasible weight management strategy in women living with overweight/obesity and HIV, receiving DTG-based treatment in a resource-limited community. These findings will ensure that the forthcoming TRE randomised controlled trial is adapted and optimised to the local South African context.

Background Obesity is associated with a change in high-density lipoprotein (HDL) function and subclass. Exercise training reduces cardiovascular risk in obese patients. We aimed to explore the effect of an exercise training stimulus on HDL functionality and subclass in obese women. Methods Thirty-two obese black South African women were randomly assigned to exercise (combined aerobic and resistance exercise) or control (no exercise) conditions for 12-weeks. Pre- and post-testing included venous blood sampling for analysis of lipid profile and HDL functionality, by measuring cellular cholesterol efflux capacity, reduction in endothelial vascular cell adhesion molecule (VCAM) expression (anti-inflammatory function), paraoxonase (PON) (antioxidative function) and platelet activating factor acetylhydrolase (PAF-AH) activities (anti-thrombotic function). PON-1 and PAF-AH expression were determined in serum and in isolated HDL using Western blotting. Levels of large, intermediate and small HDL subclasses were measured using the Lipoprint® system. Results Exercise training resulted in a decrease in body mass index (− 1.0 ± 0.5% vs + 1.2 ± 0.6%, p  = 0.010), PON activity (− 8.7 ± 2.4% vs + 1.1 ± 3.0%, p  = 0.021), PAF-AH serum expression (− 22.1 ± 8.0% vs + 16.9 ± 9.8, p  = 0.002), and the distribution of small HDL subclasses (− 10.1 ± 5.4% vs + 15.7 ± 6.6%, p  = 0.004) compared to controls. Exercise did not alter HDL cellular cholesterol efflux capacity and anti-inflammatory function. Conclusions These results demonstrate the potential for exercise training to modify HDL subclass distribution and HDL function in obese women. Trial registration Clinical trials number: PACTR201711002789113 .

The mechanisms that underlie exercise-induced adaptations in adipose tissue have not been elucidated, yet, accumulating studies suggest an important role for microRNAs (miRNAs). This study aimed to investigate miRNA expression in gluteal subcutaneous adipose tissue (GSAT) in response to a 12-week exercise intervention in South African women with obesity, and to assess depot-specific differences in miRNA expression in GSAT and abdominal subcutaneous adipose tissue (ASAT). In addition, the association between exercise-induced changes in miRNA expression and metabolic risk was evaluated. Women underwent 12-weeks of supervised aerobic and resistance training (n = 19) or maintained their regular physical activity during this period (n = 12). Exercise-induced miRNAs were identified in GSAT using Illumina sequencing, followed by analysis of differentially expressed miRNAs in GSAT and ASAT using quantitative real-time PCR. Associations between the changes (pre- and post-exercise training) in miRNA expression and metabolic parameters were evaluated using Spearman's correlation tests. Exercise training significantly increased the expression of miR-155-5p (1.5-fold, p = 0.045), miR-329-3p (2.1-fold, p < 0.001) and miR-377-3p (1.7-fold, p = 0.013) in GSAT, but not in ASAT. In addition, a novel miRNA, MYN0617, was identified in GSAT, with low expression in ASAT. The exercise-induced differences in miRNA expression were correlated with each other and associated with changes in high-density lipoprotein concentrations. Exercise training induced adipose-depot specific miRNA expression within subcutaneous adipose tissue depots from South African women with obesity. The significance of the association between exercise-induced miRNAs and metabolic risk warrants further investigation.