Jennifer Manne-Goehler

Background: Hypertension (HTN) constitutes a major and growing public health challenge in South Africa, a setting where HIV prevalence also remains high. Despite this dual burden, longitudinal evidence describing how individuals move through the HTN care cascade particularly comparing people living with HIV (PLHIV) and people not living with HIV (PNLHIV) remains limited. Understanding patterns of progression and regression across the cascade is essential to inform health system strategies for integrated chronic disease management. Methods and findings: We conducted a longitudinal secondary analysis using data collected from the iHEART-SA trial, implemented across nine public primary healthcare clinics in Johannesburg between August 2022 and May 2024, with follow-up through May 2025. Adults (≥18 years) receiving chronic care, with a known HIV status and a completed medical file review were included. Progression and regression were assessed across the HTN care cascade. Of 23,855 participants, 78.5% were PLHIV (median age 42 years, IQR 36–49; 69% female). The median SBP was 132 mmHg (IQR: 120–145 mmHg). Along the HTN care cascade, PLHIV were substantially more likely to remain undiagnosed compared with PNLHIV (aRR 3.40; 95% [CI 2.45, 4.73]; p < 0.001). Among those treated, PLHIV were less likely to achieve BP control (aRR 0.85; 95% [CI 0.75, 0.97]; p = 0.012). During follow-up, PLHIV experienced higher rates of cascade regression, including regression to untreated HTN (22% versus 11%; aRR 1.51; 95% [CI 1.03, 2.23]; p = 0.037) and from controlled to uncontrolled BP (aRR 1.10; 95% [CI 1.02, 1.18]; p = 0.010). The main study limitations were the use of routinely collected clinical data, variable follow-up, and treatment ascertainment based on documented medication use. Conclusions: PLHIV had lower HTN diagnosis and higher regression, including treatment discontinuation and loss of BP control, underscoring persistent gaps in longitudinal HTN management within HIV programmes and the need for integrated and targeted chronic care models that ensure treatment continuity and sustained control.

Background: In the Liraglutide for Obesity in HIV (LIROH) trial, we evaluated the efficacy and acceptability of liraglutide plus lifestyle counselling on weight and cardiometabolic health markers, along with the effect of discontinuation of therapy, among people with HIV (PWH) and a body mass index (BMI) ≥ 30 kg/m2 in rural South Africa. Methods: From May – September 2024, we enrolled 40 PWH in KwaZulu-Natal in a Phase IV, open-label clinical trial of liraglutide 3.0 mg daily for 12 weeks. Key cardiometabolic health outcomes included changes in weight, waist circumference, and hemoglobin A1c (HbA1c). We also assessed depression, quality of life (QoL) and sleep quality. We also assessed acceptability of the intervention based on enrollment fraction and retention at 12 weeks and 24 weeks. Results: We screened 52 participants, of whom 44 (85%) were eligible and 40 (91%) consented to enroll. Thirty-eight (95%) completed the study, with 2 (5%) discontinuing treatment due to relocation. Participants experienced substantial reductions in weight and waist circumference, and mean HbA1c (Weight: -2.9% [(-1.0–4.5%]; waist: -5.6 cm [-8.2 to -2.9]; HbA1c: -0.3% [-0.4 to -0.2]). Moreover, depressive symptoms, sleep quality, and psychological QoL all improved significantly with treatment. Weight and waist circumference rebounded significantly off treatment. The changes in depression, sleep quality and QoL were negligible post-treatment. Conclusions: This trial is among the first studies of GLP-1 RAs in Southern Africa and demonstrates that this class for obesity treatment among PWH in this region has efficacy to improve metabolic health and that the study intervention was acceptable in this population.

Background: Liver disease is an important cause of morbidity and mortality among people with HIV (PWH). Steatotic liver disease (SLD) is a leading cause of liver disease among PWH in the Global North. However, there is a dearth of data on the epidemiology of SLD in sub-Saharan Africa. Methods: We analyzed computed tomography images from a completed cohort study composed of ambulatory people with and without HIV. We defined SLD as 1 or more of the following: mean liver attenuation (density) <40 Hounsfield units, mean liver to mean spleen attenuation ratio <1, or a Hounsfield unit difference <1 between the mean attenuation values of the liver and spleen. We fit multivariable regression models to evaluate the association of HIV with SLD. In a subanalysis to explore HIV-specific effects, we excluded those who reported high-risk alcohol consumption. Results: A total of 579 participants had interpretable liver images. The prevalence of SLD was low overall (22/579, 3.8%) and higher among PWH as compared with people without HIV (5.4% vs 2.3%, P = .056). In multivariable regression models, PWH undergoing antiretroviral therapy were more likely to have SLD (adjusted odd ratio, 2.79; 95% CI, 1.10–7.09; P = .031), even after exclusion of people with high-risk alcohol consumption (adjusted odd ratio, 2.96; 95% CI, 1.00–8.70; P = .048). Conclusions: We found a low overall prevalence of SLD in Uganda, but older PWH undergoing antiretroviral therapy had a higher prevalence of SLD than those without HIV. Variation in the prevalence of SLD in the African region may be due to the variability in the methods used.

Background: Tenofovir disoproxil fumarate, lamivudine and dolutegravir (TLD) have become the first‐line antiretroviral regimen in national HIV treatment programs throughout Southern Africa, including in South Africa. This is largely due to the excellent efficacy, tolerability and affordability. However, this transition to TLD has also been associated with excess weight gain and new‐onset obesity in both new initiators of antiretroviral therapy (ART) and those who transition to TLD. Methods: We conducted one‐time, in‐depth, semi‐structured interviews with 26 overweight or obese people living with HIV with a body mass index ≥30 kg/m ² in rural KwaZulu‐Natal. The Causal Continuum Model for Obesity was used to guide the development of data collection instruments and the analysis. Results: Most participants expressed a wish for a slightly smaller body size as ideal. However, they simultaneously rejected the notion of a desire to appear thin, associating thinness with illness. They also expressed concern about stigma from family and friends if they were to experience rapid or large weight loss. We also found that overweight and obese people living with HIV in this rural community consistently associated large body sizes with an increased risk of high blood pressure, diabetes and other health complications. Lastly, the participants expressed an interest in exercise‐based and pharmacologic interventions to prevent weight gain or promote weight loss in particular, but had little interest in diet modification for this purpose. Conclusion: Efforts to develop interventions to address obesity in people living with HIV should consider those that include exercise or pharmacologic anti‐obesity therapies in their design and implementation.

Background: People with HIV (PWH) have experienced excess weight gain on tenofovir, lamivudine, and dolutegravir (TLD). The contribution of lifestyle behavior to this weight gain is poorly understood. Methods: The Population Effectiveness of Dolutegravir Implementation in sub-Saharan Africa (DISCO Study) was a prospective observational cohort study that followed participants in KwaZulu-Natal, South Africa, transitioning to TLD. Our primary outcome of interest was clinically significant weight gain, defined as ≥10% increase from baseline to 48 weeks. Primary exposures of interest were (1) fruit intake (servings/week), (2) vegetable intake (servings/week), (3) fast food intake frequency, (4) fried food intake frequency, (5) sugar-sweetened beverage (SSB) intake frequency, and (6) physical activity (MET-min/week). We compared changes in each exposure for 48 weeks among those with and without clinically significant weight gain and fit logistic regression models to examine adjusted relationships between these exposures and weight gain. Results: Among 367 participants, the median age was 42 years, 78% were woman, and 18.0% experienced clinically significant weight gain during 48 weeks. The mean change in fruit intake was higher among participants with versus without clinically significant weight gain (0.21 servings/week [95% CI: −0.9 to 1.3] versus −1.07 servings/week [95% CI: −1.5 to −0.6], respectively) ( P = 0.015). However, no significant differences in other behaviors were observed and no dietary and activity behaviors correlated with weight change in multivariable regression models. Discussion: Weight gain in people transitioning to TLD was not strongly linked to lifestyle. Interventions targeting diet and exercise may be unlikely to mitigate weight gain in this population.

Background: How anti-SARS-CoV-2 monoclonal antibodies (mAbs) change subsequent vaccine responses remains uncertain. Methods: We conducted a prospective, phase IV, open-label study of adults who received mRNA-1273 or BNT162b2. Cohort 1 included outpatients with acute COVID-19 previously randomized to mAbs (tixagevimab/cilgavimab or amubarvimab/romlusevimab), camostat, or placebo in ACTIV-2/A5401. Cohort 2 included unvaccinated adults without reported prior COVID-19 and was analyzed as naive or non-naive by baseline neutralizing antibodies (nAbs). We measured binding IgG, nAbs, spike-specific memory B cells, and CD4+/CD8+ T cells at baseline and days 28, 56, and 140. Results: Forty-three participants were analyzed. At day 140, nAb titers were lower among prior mAb recipients and COVID-19–naive participants than among placebo/camostat recipients and those with evidence of prior infection (overall P = .018). RBD-specific, but not spike-specific, memory B cells were reduced after prior mAb therapy at days 56 and 140. Frequency of spike-specific CD4 + and CD8+ T-cell responses did not differ by prior mAb exposure. Adverse events were mostly grade 1–2 and consistent with vaccine trials. Conclusions: Prior anti-SARS-CoV-2 mAb treatment limits endogenous RBD-focused B-cell responses to later mRNA vaccination without measurably affecting T-cell immunity. Timing of vaccination after mAb therapy may matter and warrants study. Clinical Trials Registration: NCT04952402.

Background: Hypertension (HTN) constitutes a major and growing public health challenge in South Africa, a setting where HIV prevalence also remains high. Despite this dual burden, longitudinal evidence describing how individuals move through the HTN care cascade particularly comparing people living with HIV (PLHIV) and people not living with HIV (PNLHIV) remains limited. Understanding patterns of progression and regression across the cascade is essential to inform health system strategies for integrated chronic disease management. Methods and Findings: We conducted a longitudinal secondary analysis using data collected from the iHEART-SA trial, which was implemented across nine public primary healthcare clinics in Johannesburg between August 2022 and May 2024. with follow-up through May 2025. Adults (≥18 years) with a known HIV status and a completed medical file review were included. Progression and regression were assessed across the HTN care cascade. Of 23 855 participants, 78.5% were PLHIV (median age 42 years, IQR 36–49; 69% female). Overall, 34.4% had high blood pressure (BP), with prevalence higher among PNLHIV than PLHIV (53.5% vs 29.3%; p<0.001). Along the HTN care cascade, PLHIV were substantially more likely to remain undiagnosed compared with PNLHIV (aRR 3.40; 95% CI 3.12–3.71). Among those treated, PLHIV were less likely to achieve BP control (aRR 0.83; 95% CI 0.75–0.91). During follow-up, PLHIV experienced higher rates of cascade regression, including regression to untreated HTN (29% vs 19%; aRR 1.51; 95% CI 1.35–1.70) and from controlled to uncontrolled BP (aRR 1.12; 95% CI 1.05–1.18). Conclusions: Despite frequent health-system contact, PLHIV had lower HTN diagnosis and higher regression, including treatment discontinuation and loss of BP control, underscoring persistent gaps in longitudinal HTN management within HIV programmes and the need for integrated and targeted chronic care models that ensure treatment continuity and sustained control.

Background: Effective cardiovascular disease (CVD) risk management is essential for optimal diabetes care. Here, we estimated the prevalence and determinants of CVD risk factor control among individuals with diagnosed diabetes in Mexico. Methods: We analyzed data from individuals ≥20 years with diagnosed diabetes from 2016 to 2023 Mexican National Health and Nutrition Surveys. We estimated the prevalence of glycemic, blood pressure, noncurrent smoking, low‐density lipoprotein cholesterol, and combined CVD risk factor control. We estimated use of blood pressure‐lowering, cholesterol‐lowering, and glucose‐lowering medication and explored determinants of control achievement using logistic regression. Results: We analyzed data from 2916 participants, representing 43.2 million adults with diagnosed diabetes during 2016 to 2023. In 2023, glycemic control was 29% (95% CI, 21%–38%), blood pressure control 22.9% (95% CI, 14%–31%), and noncurrent smoking 89% (95% CI, 81%–96%). The prevalence of high or very‐high CVD risk using Systematic Coronary Risk Evaluation 2‐Diabetes increased from 59.8% (95% CI, 52.1%–67.0%) in 2016 to 68.4% (95% CI, 55.6%–78.9%) in 2023, representing ~5.1 million adults. Low‐density lipoprotein cholesterol control increased from 2.8% (95% CI, 1.2%–4.4%) in 2016 to 6.6% (95% CI, 1.9%–11.2%) in 2023 and statin use from 5.5% in 2016 to 63% in 2023. Combined risk factor control achievement was low due to suboptimal low‐density lipoprotein cholesterol control and was more likely achieved in women, younger individuals, and those with college education or living in states with higher socioeconomic position. Conclusions: Despite increasing CVD risk during this period, glycemic and CVD risk factor management for adults with diabetes in Mexico remains suboptimal. Our findings suggest a need for strategies to improve CVD risk management to reduce diabetes‐related mortality and complications.