Prior tuberculosis, radiographic lung abnormalities and prevalent diabetes in rural South Africa.

BACKGROUND: Growing evidence suggests that chronic inflammation caused by tuberculosis (TB) may increase the incidence of diabetes. However, the relationship between post-TB pulmonary abnormalities and diabetes has not been well characterized. METHODS: We analyzed data from a cross-sectional study in KwaZulu-Natal, South Africa, of people 15 years and older who underwent chest X-ray and diabetes screening with hemoglobin A1c testing. The analytic sample was restricted to persons with prior TB, defined by either (1) a self-reported history of TB treatment, (2) radiologist-confirmed prior TB on chest radiography, and (3) a negative sputum culture and GeneXpert. Chest X-rays of all participants were evaluated by the study radiologist to determine the presence of TB lung abnormalities. To assess the relationships between our outcome of interest, prevalent diabetes (HBA1c ≥6.5%), and our exposure of interest, chest X-ray abnormalities, we fitted logistic regression models adjusted for potential clinical and demographic confounders. In secondary analyses, we used the computer-aided detection system CAD4TB, which scores X-rays from 10 to 100 for detection of TB disease, as our exposure interest, and repeated analyses with a comparator group that had no history of TB disease. RESULTS: In the analytic cohort of people with prior TB (n = 3,276), approximately two-thirds (64.9%) were women, and the average age was 50.8 years (SD 17.4). The prevalence of diabetes was 10.9%, and 53.0% of people were living with HIV. In univariate analyses, there was no association between diabetes prevalence and radiologist chest X-ray abnormalities (OR 1.23, 95%CI 0.95-1.58). In multivariate analyses, the presence of pulmonary abnormalities was associated with an 29% reduction in the odds of prevalent diabetes (aOR 0.71, 95%CI 0.53-0.97, p = 0.030). A similar inverse relationship was observed for diabetes with each 10-unit increase in the CAD4TB chest X-ray scores among people with prior TB (aOR 0.92, 95%CI 0.87-0.97; p = 0.002), but this relationship was less pronounced in the no TB comparator group (aOR 0.96, 95%CI 0.94-0.99). CONCLUSIONS: Among people with prior TB, pulmonary abnormalities on digital chest X-ray are inversely associated with prevalent diabetes. The severity of radiographic post-TB lung disease does not appear to be a determinant of diabetes in this South African population.

Blood pressure increases are associated with weight gain and not antiretroviral regimen or kidney function: a secondary analysis from the ADVANCE trial in South Africa.

INTRODUCTION: Recent evidence has raised questions about whether newer HIV treatment regimens, including dolutegravir (DTG) and tenofovir alafenamide (TAF), are associated with increases in blood pressure (BP). METHODS: We assessed changes in BP by treatment regimen and evaluated the relative contribution of kidney function and weight gain to these changes among participants in the ADVANCE phase-3 trial clinical trial in South Africa (study dates: January 2017-February 2022). Our primary outcome of interest was a change in systolic BP (SBP) at 96 and 192 weeks, among those not receiving antihypertensive medication. The secondary outcome was treatment-emergent hypertension at these same time points, defined as BP ≥140/90 mmHg on two occasions, or initiation of antihypertensive medication after week 4 among individuals without hypertension at enrolment. We used linear regression to evaluate the relationship between change in estimated glomerular filtration rate (eGFR) and change in SBP; and Poisson regression to evaluate the relationship between change in eGFR and treatment-emergent hypertension at each time point. All models were adjusted for age, sex, treatment group and change in body mass index (BMI). RESULTS: Over 96 weeks, the average changes in SBP were 1.7 mmHg (95% CI: 0.0-3.4), -0.5 mmHg (95% CI: -2.2 to 1.7) and -2.1 mmHg (95% CI: -3.8 to 0.4) in the TAF/emtricitabine (FTC)/DTG, tenofovir disoproxil fumarate (TDF)/FTC/DTG and TDF/FTC/efavirenz (EFV) groups, respectively. This difference was significant for the TAF/FTC/DTG compared to the TDF/FTC/EFV group (p = 0.002). Over 96 weeks, 18.2% (95% CI: 13.4-22.9), 15.4% (95% CI: 11.0-19.9) and 13.3% (95% CI: 8.9-17.6) of participants developed treatment-emergent hypertension, respectively. In adjusted models, there was no significant relationship between change in eGFR and either outcome. Change in BMI was significantly associated with an increase in SBP, while age was associated with an increased risk of treatment-emergent hypertension. Adjustment for BMI also mitigated the unadjusted relationship between HIV treatment regimen and SBP where present. CONCLUSIONS: In the ADVANCE cohort, weight gain and age accounted for increases in BP and risk of treatment-emergent hypertension. HIV treatment programmes may need to integrate the management of obesity and hypertension into routine care. CLINICAL TRIAL NUMBER: NCT03122262.

Frailty progression in adults aged 40 years and older in rural Burkina Faso: a longitudinal, population-based study.

BACKGROUND: Little is known about ageing and frailty progression in low-income settings. We aimed to describe frailty changes over time in individuals living in rural Burkina Faso and to assess which sociodemographic, disability, and multimorbidity factors are associated with frailty progression and mortality. METHODS: This longitudinal, population-based study was conducted at the Nouna Health and Demographic Surveillance Systems (HDSS) site in northwestern Burkina Faso. Eligible participants were aged 40 years or older and had been primarily resident in a household within the HDSS area for at least the past 6 months before the baseline survey and were selected from the 2015 HDSS household census using a stratified random sample of adults living in unique households within the area. Participants were interviewed in their homes in 2018 (baseline), 2021 (follow-up), or both. We derived the Fried frailty score for each participant at each timepoint using data on grip strength, gait speed, self-reported weight loss, self-reported exhaustion, and physical activity, and described changes in frailty status (no frailty, pre-frailty, or frailty) between 2018 and 2021. We used multivariate regression models to assess factors (ie, sex, age, marital status, educational attainment, wealth quintile, WHO Disability Assessment Schedule (WHODAS) score, and multimorbidity) associated with frailty progression (either worsening frailty status or dying, compared with frailty status remaining the same or improving) and with mortality, and developed sequential models: unadjusted, adjusting for sociodemographic factors (sex, age, marital status, educational attainment, and wealth quintile), and adjusting for sociodemographic factors, disability, and multimorbidity. FINDINGS: Between May 25 and July 19, 2018, and between July 1 and Aug 22, 2021, 5952 individuals were invited to participate: 1709 (28·7%) did not consent, 1054 (17·8%) participated in 2018 only and were lost to follow-up, 1214 (20·4%) participated in 2021 only, and 1975 (33·2%) were included in both years or died between years. Of 1967 participants followed up with complete demographic data, 190 (9·7%) were frail or unable to complete the frailty assessment in 2018, compared with 77 (3·9%) in 2021. Between 2018 and 2021, frailty status improved in 567 (28·8%) participants and worsened in 327 (16·6%), and 101 (5·1%) participants died. The relative risk of frailty status worsening or of dying (compared with frailty impRoving or no change) increased with age and WHODAS score, whereas female sex appeared protective. After controlling for all sociodemographic factors, multimorbidity, and WHODAS score, odds of mortality were 1·07 (odds ratio 2·07, 95% CI 1·05-4·09) times higher among pre-frail individuals and 1·1 (2·21, 0·90-5·41) times higher among frail individuals than among non-frail individuals. INTERPRETATION: Frailty status was highly dynamic in this low-income setting and appears to be modifiable. Given the rapid increase in the numbers of older adults in low-income or middle-income countries, understanding the behaviour of frailty in these settings is of high importance for the development of policies and health systems to ensure the maintenance of health and wellbeing in ageing populations. Future work should focus on designing context-appropriate interventions to improve frailty status. FUNDING: Alexander Von Humboldt Foundation, Institute for Global Innovation, University of Birmingham, and Wellcome Trust.

The HIV Care Cascade for Older Adults in Rural South Africa: A Longitudinal Cohort Study (2014-2019).

BACKGROUND: As people with HIV grow older, stable engagement in care is essential for healthy aging. We evaluate the HIV care cascade for older adults in rural South Africa at 2 time points cross-sectionally and assess movement in the cascade over time. SETTING: We evaluated the cascade stage at waves 1 (2014-2015) and 2 (2018-2019) of Health and Aging in Africa: A Longitudinal Study of an INDPETH Community in South Africa, a population-based longitudinal cohort study in Mpumalanga Province, South Africa. METHODS: Biomarker screening defined cascade stages [HIV+/no antiretroviral therapy (ART); ART+/unsuppressed viral load; ART+/suppressed viral load]. Between-wave probability of death, cascade progression, regression, cascade transitions, and sociodemographic predictors were assessed with Poisson regression. The impact of death was considered using the Fine and Gray competing risk model. RESULTS: We observed a higher prevalence of antiretroviral therapy with viral suppression over time (50% in wave 1 vs. 70% in wave 2). Among those alive, the oldest age group (70+ years old) was most likely to have cascade progression [adjusted risk ratio for treatment initiation vs. 40-49 years old: 1.38 (95% confidence interval: 1.02 to 1.86)]. However, there was a significant risk of death and cascade regression. Death between waves reached 40% for 70+-year-olds who were ART+/unsuppressed. In competing risk models, older age was associated with equivalent or less cascade progression. CONCLUSION: Older age groups who were unsuppressed on treatment and men had poorer cascade outcomes. Improvements observed in HIV treatment coverage over time for older adults must be interpreted in the context of the high risk of death for older HIV-positive adults, especially among those failing treatment.

Undernutrition as a risk factor for tuberculosis disease.

BACKGROUND: Tuberculosis (TB) is a leading cause of mortality due to an infectious disease, with an estimated 1.6 million deaths due to TB in 2022. Approximately 25% of the global population has TB infection, giving rise to 10.6 million episodes of TB disease in 2022. Undernutrition is a key risk factor for TB and was linked to an estimated 2.2 million TB episodes in 2022, as outlined in the World Health Organization (WHO) Global Tuberculosis Report. OBJECTIVES: To determine the prognostic value of undernutrition in the general population of adults, adolescents, and children for predicting tuberculosis disease over any time period. SEARCH METHODS: We searched the literature databases MEDLINE (via PubMed) and WHO Global Index Medicus, as well as the WHO International Clinical Trials Registry Platform (ICTRP) on 3 May 2023 (date of last search for all databases). We placed no restrictions on the language of publication. SELECTION CRITERIA: We included retrospective and prospective cohort studies, irrespective of publication status or language. The target population comprised adults, adolescents, and children from diverse settings, encompassing outpatient and inpatient cohorts, with varying comorbidities and risk of exposure to tuberculosis. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology and the Quality In Prognosis Studies (QUIPS) tool to assess the risk of bias of the studies. Prognostic factors included undernutrition, defined as wasting, stunting, and underweight, with specific measures such as body mass index (BMI) less than two standard deviations below the median for children and adolescents and low BMI scores (< 18.5) for adults and adolescents. Prognostication occurred at enrolment/baseline. The primary outcome was the incidence of TB disease. The secondary outcome was recurrent TB disease. We performed a random-effects meta-analysis for the adjusted hazard ratios (HR), risk ratios (RR), or odds ratios (OR), employing the restricted maximum likelihood estimation. We rated the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 51 cohort studies with over 27 million participants from the six WHO regions. Sixteen large population-based studies were conducted in China, Singapore, South Korea, and the USA, and 25 studies focused on people living with HIV, which were mainly conducted in the African region. Most studies were in adults, four in children, and three in children and adults. Undernutrition as an exposure was usually defined according to standard criteria; however, the diagnosis of TB did not include a confirmatory culture or molecular diagnosis using a WHO-approved rapid diagnostic test in eight studies. The median follow-up time was 3.5 years, and the studies primarily reported an adjusted hazard ratio from a multivariable Cox-proportional hazard model. Hazard ratios (HR) The HR estimates represent the highest certainty of the evidence, explored through sensitivity analyses and excluding studies at high risk of bias. We present 95% confidence intervals (CI) and prediction intervals, which present between-study heterogeneity represented in a measurement of the variability of effect sizes (i.e. the interval within which the effect size of a new study would fall considering the same population of studies included in the meta-analysis). Undernutrition may increase the risk of TB disease (HR 2.23, 95% CI 1.83 to 2.72; prediction interval 0.98 to 5.05; 23 studies; 2,883,266 participants). The certainty of the evidence is low due to a moderate risk of bias across studies and inconsistency. When stratified by follow-up time, the results are more consistent across < 10 years follow-up (HR 2.02, 95% CI 1.74 to 2.34; prediction interval 1.20 to 3.39; 22 studies; 2,869,077 participants). This results in a moderate certainty of evidence due to a moderate risk of bias across studies. However, at 10 or more years of follow-up, we found only one study with a wider CI and higher HR (HR 12.43, 95% CI 5.74 to 26.91; 14,189 participants). The certainty of the evidence is low due to the moderate risk of bias and indirectness. Odds ratio (OR) Undernutrition may increase the odds of TB disease, but the results are uncertain (OR 1.56, 95% CI 1.13 to 2.17; prediction interval 0.61 to 3.99; 8 studies; 173,497 participants). Stratification by follow-up was not possible as all studies had a follow-up of < 10 years. The certainty of the evidence is very low due to the high risk of bias and inconsistency. Contour-enhanced funnel plots were not reported due to the few studies included. Risk ratio (RR) Undernutrition may increase the risk of TB disease (RR 1.95, 95% CI 1.72 to 2.20; prediction interval 1.49 to 2.55; 4 studies; 1,475,867 participants). Stratification by follow-up was not possible as all studies had a follow-up of < 10 years. The certainty of the evidence is low due to the high risk of bias. Contour-enhanced funnel plots were not reported due to the few studies included. AUTHORS' CONCLUSIONS: Undernutrition probably increases the risk of TB two-fold in the short term (< 10 years) and may also increase the risk in the long term (> 10 years). Policies targeted towards the reduction of the burden of undernutrition are not only needed to alleviate human suffering due to undernutrition and its many adverse consequences, but are also an important part of the critical measures for ending the TB epidemic by 2030. Large population-based cohorts, including those derived from high-quality national registries of exposures (undernutrition) and outcomes (TB disease), are needed to provide high-certainty estimates of this risk across different settings and populations, including low and middle-income countries from different WHO regions. Moreover, studies including children and adolescents and state-of-the-art methods for diagnosing TB would provide more up-to-date information relevant to practice and policy. FUNDING: World Health Organization (203256442). REGISTRATION: PROSPERO registration: CRD42023408807 Protocol: https://doi.org/10.1002/14651858.CD015890.

The Association Between Depressive Symptoms, Access to Diabetes Care, and Glycemic Control in Five Middle-Income Countries.

OBJECTIVE: The relationship between depression, diabetes, and access to diabetes care is established in high-income countries (HICs) but not in middle-income countries (MICs), where contexts and health systems differ and may impact this relationship. In this study, we investigate access to diabetes care for individuals with and without depressive symptoms in MICs. RESEARCH DESIGN AND METHODS: We analyzed pooled data from nationally representative household surveys across Brazil, Chile, China, Indonesia, and Mexico. Validated survey tools Center for Epidemiologic Studies Depression Scale Revised, Composite International Diagnostic Interview, Short Form, and Patient Health Questionnaire identified participants with depressive symptoms. Diabetes, defined per World Health Organization Package of Essential Noncommunicable Disease Interventions guidelines, included self-reported medication use and biochemical data. The primary focus was on tracking diabetes care progression through the stages of diagnosis, treatment, and glycemic control. Descriptive and multivariable logistic regression analyses, accounting for gender, age, education, and BMI, examined diabetes prevalence and care continuum progression. RESULTS: The pooled sample included 18,301 individuals aged 50 years and above; 3,309 (18.1%) had diabetes, and 3,934 (21.5%) exhibited depressive symptoms. Diabetes prevalence was insignificantly higher among those with depressive symptoms (28.9%) compared with those without (23.8%, P = 0.071). Co-occurrence of diabetes and depression was associated with increased odds of diabetes detection (odds ratio [OR] 1.398, P < 0.001) and treatment (OR 1.344, P < 0.001), but not with higher odds of glycemic control (OR 0.913, P = 0.377). CONCLUSIONS: In MICs, individuals aged 50 years and older with diabetes and depression showed heightened diabetes identification and treatment probabilities, unlike patterns seen in HICs. This underscores the unique interplay of these conditions in different income settings.

Chagas disease in the United States: a call for increased investment and collaborative research.

Chagas disease, caused by the protozoan Trypanosoma cruzi, is a highly overlooked parasitic infection within the United States. It affects an estimated 300,000 individuals, often remaining asymptomatic for years before triggering severe complications such as cardiomyopathy in 30-40% of cases. While many contract the disease in Latin America, its transmission by local vectors in the southern U.S. presents a significant challenge. Unfortunately, limited access to diagnosis and treatment persists, alongside unresolved gaps in healthcare systems and disease pathogenesis. In this viewpoint, we discuss the need for focused research and public health initiatives, with U.S. research institutions playing a crucial role in developing new treatments and identifying biomarkers. Furthermore, investigating the genetic variations of T. cruzi between North and South America is vital for improving diagnostic and treatment strategies. Urgent action is required to implement national and local programs, bolstering healthcare responses and advancing research efforts.Q4As per journal style section heading 'Introduction' is mandatory, hence we have introduced the heading. Please check, and correct if necessary.ResolvedQ5If there are any drug dosages in your article, please verify them and indicate that you have done so by initialing this query.ResolvedQ6Please supply the year of publication.ResolvedFootnoteView Edit Log9.

Multiple cardiovascular risk factor care in 55 low- and middle-income countries: A cross-sectional analysis of nationally-representative, individual-level data from 280,783 adults.

The prevalence of multiple age-related cardiovascular disease (CVD) risk factors is high among individuals living in low- and middle-income countries. We described receipt of healthcare services for and management of hypertension and diabetes among individuals living with these conditions using individual-level data from 55 nationally representative population-based surveys (2009-2019) with measured blood pressure (BP) and diabetes biomarker. We restricted our analysis to non-pregnant individuals aged 40-69 years and defined three mutually exclusive groups (i.e., hypertension only, diabetes only, and both hypertension-diabetes) to compare individuals living with concurrent hypertension and diabetes to individuals with each condition separately. We included 90,086 individuals who lived with hypertension only, 11,975 with diabetes only, and 16,228 with hypertension-diabetes. We estimated the percentage of individuals who were aware of their diagnosis, used pharmacological therapy, or achieved appropriate hypertension and diabetes management. A greater percentage of individuals with hypertension-diabetes were fully diagnosed (64.1% [95% CI: 61.8-66.4]) than those with hypertension only (47.4% [45.3-49.6]) or diabetes only (46.7% [44.1-49.2]). Among the hypertension-diabetes group, pharmacological treatment was higher for individual conditions (38.3% [95% CI: 34.8-41.8] using antihypertensive and 42.3% [95% CI: 39.4-45.2] using glucose-lowering medications) than for both conditions jointly (24.6% [95% CI: 22.1-27.2]).The percentage of individuals achieving appropriate management was highest in the hypertension group (17.6% [16.4-18.8]), followed by diabetes (13.3% [10.7-15.8]) and hypertension-diabetes (6.6% [5.4-7.8]) groups. Although health systems in LMICs are reaching a larger share of individuals living with both hypertension and diabetes than those living with just one of these conditions, only seven percent achieved both BP and blood glucose treatment targets. Implementation of cost-effective population-level interventions that shift clinical care paradigm from disease-specific to comprehensive CVD care are urgently needed for all three groups, especially for those with multiple CVD risk factors.

Regional variation in weight change after the transition to dolutegravir in Uganda and South Africa.

BACKGROUND: People with HIV (PWH) on integrase inhibitor-based regimens may be at risk of excess weight gain, but it is unclear if this risk is consistent across settings. We assessed weight change over 48 weeks among PWH who were transitioned to tenofovir disoproxil fumarate/lamivudine/dolutegravir (TLD). DESIGN: We conducted a prospective cohort study at public-sector HIV clinics in Uganda and South Africa. METHODS: Eligible participants were adults who were transitioned to TLD. Weight was measured at enrollment, 24-, and 48-weeks post TLD transition. Our outcomes were weight change, change in waist circumference, and clinically significant weight gain, defined as ≥10% increase in weight from baseline, over 48 weeks. We used linear mixed-effects regression models, adjusted for demographic factors, to estimate weight gain and identify risk factors. RESULTS: Weight data were available for 428 participants in Uganda and 367 in South Africa. The mean weight change was 0.6 kg [95% CI: 0.1-1.0] in Uganda and 2.9 kg [2.3-3.4] in South Africa ( P  < 0.001). The mean change in waist circumference was 0.8 cm [95% CI: 0.0-1.5]) in Uganda and 2.3 cm [95% CI: 1.4-3.2] in South Africa ( P  = 0.012). Clinically significant weight gain occurred in 9.8% [7.0-12.6] of participants in Uganda and 18.0% [14.1-21.9] in South Africa ( P  < 0.001). After adjustment, PWH gained significantly less weight in Uganda than in South Africa. CONCLUSIONS: PWH in South Africa experienced significantly greater weight gain and increases in waist circumference compared to Uganda. Strategies to address weight gain in PWH should be carefully considered and may vary by region.

The prevalence of cardiovascular disease risk factors among adults living in extreme poverty.

Evidence on cardiovascular disease (CVD) risk factor prevalence among adults living below the World Bank's international line for extreme poverty (those with income <$1.90 per day) globally is sparse. Here we pooled individual-level data from 105 nationally representative household surveys across 78 countries, representing 85% of people living in extreme poverty globally, and sorted individuals by country-specific measures of household income or wealth to identify those in extreme poverty. CVD risk factors (hypertension, diabetes, smoking, obesity and dyslipidaemia) were present among 17.5% (95% confidence interval (CI) 16.7-18.3%), 4.0% (95% CI 3.6-4.5%), 10.6% (95% CI 9.0-12.3%), 3.1% (95% CI 2.8-3.3%) and 1.4% (95% CI 0.9-1.9%) of adults in extreme poverty, respectively. Most were not treated for CVD-related conditions (for example, among those with hypertension earning <$1.90 per day, 15.2% (95% CI 13.3-17.1%) reported taking blood pressure-lowering medication). The main limitation of the study is likely measurement error of poverty level and CVD risk factors that could have led to an overestimation of CVD risk factor prevalence among adults in extreme poverty. Nonetheless, our results could inform equity discussions for resource allocation and design of effective interventions.

Final 192-Week Efficacy and Safety Results of the ADVANCE Trial, Comparing 3 First-line Antiretroviral Regimens.

Background: ADVANCE compared 3 World Health Organization-recommended first-line regimens in participants with HIV who were antiretroviral naive. Methods: This randomized, open-label, noninferiority trial enrolled participants living with HIV with no antiretroviral exposure in the previous 6 months to 1 of the following arms: tenofovir alafenamide (TAF) / emtricitabine (FTC) + dolutegravir (DTG) (2 tablets), tenofovir disoproxil fumarate (TDF) / FTC + DTG (2 tablets), or a fixed-dose combination of TDF / FTC / efavirenz (EFV) (1 tablet). We report the final safety and efficacy data up to 192 weeks. Results: Repeat consent from the original 351 participants randomized to each arm was obtained from 230 participants (66%) in the TAF/FTC + DTG arm, 209 (60%) in the TDF/FTC + DTG arm, and 183 (52%) in the TDF/FTC/EFV arm. At 192 weeks, 213 (61%) of the original 351 participants in the TAF/FTC + DTG arm, 195 (56%) in the TDF/FTC + DTG arm, and 172 (49%) in the TDF/FTC/EFV arm had confirmed RNA <50 copies/mL, with low virologic failure in all groups and no significant integrase inhibitor mutations in any arm. Mean weight gain was 8.9 kg (SD, 7.1) in the TAF/FTC + DTG arm, 5.9 kg (SD, 7.1) in the TDF/FTC + DTG arm, and 3.2 kg (SD, 8.1) in the TDF/FTC/EFV arm at 192 weeks from baseline and was greatest among women, those taking TAF, and those with lower baseline CD4 counts. The weight trajectory slowed after week 96. There were few clinical events and minor laboratory changes and differences among arms after 96 weeks. There were no significant differences in treatment-emergent hypertension or pregnancy outcomes by arm. Conclusions: High viral suppression was seen across arms, with no resistance to DTG. Weight gain continued but slowed after 96 weeks, with few clinical events or laboratory changes.

Cytomegalovirus IgG is Associated With Physical Function But Not Muscle Density in People With HIV.

BACKGROUND: Cytomegalovirus (CMV) seropositivity is associated with poor outcomes, including physical function impairment, in people without HIV. We examined associations between CMV IgG titer and physical function in virologically suppressed people with HIV (PWH). METHODS: REPRIEVE is a double-blind randomized trial evaluating pitavastatin for primary prevention of atherosclerotic cardiovascular disease in PWH. This analysis focused on participants enrolled in a substudy with additional biomarker testing, imaging [coronary CT angiography], and physical function measures at entry. CMV IgG was measured using quantitative enzyme immunoassay, physical function by Short Physical Performance Battery, and muscle density and area by CT. Associations between CMV IgG (risk factor) and outcomes were evaluated using the partial Spearman correlation and linear and log-binomial regression. RESULTS: Among 717 participants, 82% male, the median CMV IgG was 2716 (Q1, Q3: 807, 6672) IU/mL, all above the limit of quantification. Among 631 participants with imaging, there was no association between CMV IgG and CT-based muscle density or area, controlling for age (r = -0.03 and r = -0.01, respectively; P ≥ 0.38). Among 161 participants with physical function data, higher CMV IgG was associated with poorer overall modified Short Physical Performance Battery score ( P = 0.02), adjusted for age, nadir CD4, and high-sensitivity C-reactive protein. CONCLUSIONS: Higher CMV IgG titer was associated with poorer physical function, not explained by previous immune compromise, inflammation, or muscle density or area. Further mechanistic studies are needed to understand this association and whether CMV-specific therapy can affect physical function in PWH.

The Association Between HIV-Related Stigma and the Uptake of HIV Testing and ART Among Older Adults in Rural South Africa: Findings from the HAALSI Cohort Study.

HIV testing and antiretroviral therapy (ART) remain critical for curbing the spread of HIV/AIDS, but stigma can impede access to these services. Using data from the Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa (HAALSI), we used a multivariable logistic regression to examine the correlation between HIV-related stigma, HIV testing and ART uptake in older adults. We used four questions to measure stigma, with three assessing social stigma (reflecting social distancing preferences) and one assessing anticipated stigma (disclosure concern). We combined the three social stigma questions to generate a social stigma score ranging from 0 to 3, with higher scores indicating higher stigma. Anticipated stigma was prevalent 85% (95% CI 0.84-0.86), and social stigma was also frequent 25% (95% CI 0.24-0.27). Higher social stigma scores correlated with decreased HIV testing for all participants with social stigma. Compared to those with a score of 0, odds of testing decreased with higher stigma scores (OR = 0.66, 95% CI 0.53-0.81, p = 0.000) for a score of 1 and (OR = 0.56, 95% CI 0.38-0.83, p = 0.004) for a score of 3. ART uptake also decreased with higher social stigma scores among people living with HIV (PLWH), although it was significant for those with a score of 2 (OR = 0.41, 95% CI 0.19-0.87, p = 0.020). These findings emphasize that HIV-related stigma hampers testing and ART uptake among older adults in rural South Africa. Addressing stigma is crucial for improving testing rates, early diagnosis, and treatment initiation among the older population and achieving UNAIDS 95-95-95 targets.

Hypertension care cascades and reducing inequities in cardiovascular disease in low- and middle-income countries.

Improving hypertension control in low- and middle-income countries has uncertain implications across socioeconomic groups. In this study, we simulated improvements in the hypertension care cascade and evaluated the distributional benefits across wealth quintiles in 44 low- and middle-income countries using individual-level data from nationally representative, cross-sectional surveys. We raised diagnosis (diagnosis scenario) and treatment (treatment scenario) levels for all wealth quintiles to match the best-performing country quintile and estimated the change in 10-year cardiovascular disease (CVD) risk of individuals initiated on treatment. We observed greater health benefits among bottom wealth quintiles in middle-income countries and in countries with larger baseline disparities in hypertension management. Lower-middle-income countries would see the greatest absolute benefits among the bottom quintiles under the treatment scenario (29.1 CVD cases averted per 1,000 people living with hypertension in the bottom quintile (Q1) versus 17.2 in the top quintile (Q5)), and the proportion of total CVD cases averted would be largest among the lowest quintiles in upper-middle-income countries under both diagnosis (32.0% of averted cases in Q1 versus 11.9% in Q5) and treatment (29.7% of averted cases in Q1 versus 14.0% in Q5) scenarios. Targeted improvements in hypertension diagnosis and treatment could substantially reduce socioeconomic-based inequalities in CVD burden in low- and middle-income countries.

Perceptions of Health, Body Size, and Nutritional Risk Factors for Obesity in People with HIV in South Africa.

Metabolic disease is increasing in people with HIV (PWH) in South Africa, but little is known about self-perceptions of body size, health, and nutritional behavior in this population. We performed a cross-sectional analysis of individual-level data from the 2016 South Africa Demographic and Health Survey. This survey measured HIV serostatus and body mass index (BMI). We categorized participants into six BMI groups: 18.5-22 kg/m2, 22-25 kg/m2, 25-27.5 kg/m2, 27.5-30 kg/m2, 30-35 kg/m2, and ≥ 35 kg/m2 and stratified them by HIV serostatus. Our outcomes were self-reported (1) body size and (2) health status among all participants, and intake of (3) chips and (4) sugar-sweetened beverages (SSB) in PWH. We described these metrics and used multivariable regression to evaluate the relationship between the nutritional behaviors and BMI ≥ 25 kg/m2 in PWH only, adjusting for age, sex, educational attainment, and household wealth quintile. Of 6138 participants, 1163 (19.7%) were PWH. Among PWH, < 10% with a BMI 25-30 kg/m2, < 20% with a BMI 30-35 kg/m2 and < 50% with a BMI ≥ 35 kg/m2 self-reported as overweight or obese. PWH reported being in poor health at higher rates than those without HIV at each BMI category except ≥ 35 kg/m2. In adjusted models, SSB consumption was associated with BMI ≥ 25 kg/m2 (1.13 [1.01-1.25], t-statistic = 2.14, p = 0.033) in PWH. Perceptions of body size may challenge efforts to prevent weight gain in PWH in South Africa. SSB intake reduction should be further explored as a modifiable risk factor for obesity.

From Evidence to Effectiveness: Implications of the Randomized Trial to Prevent Vascular Events in HIV Study for People With Human Immunodeficiency Virus in Low- and Middle-Income Settings.

The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) study found a 35% reduction in major adverse cardiovascular events for people with human immunodeficiency virus who received daily pitavastatin. However, how this evidence will change practice is far from certain. Here, we outline evidence gaps and political and healthcare delivery challenges that will need to be addressed for REPRIEVE to offer public health benefits in low- and middle-income countries.

Identifying sex-specific anthropometric measures and thresholds for dysglycemia screening in an HIV-endemic rural South African population.

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-value<0.001) and women (p<0.001). WC had greater discriminatory capacity than BMI to detect dysglycemia in women (p<0.001). However, BMI and WC performed similarly for men (p = 0.589). Whereas traditional WC thresholds for women (>81cm) 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.