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Crosstalk between Host Genome and Metabolome among People with HIV in South Africa.

ABSTRACT: Genome-wide association studies (GWAS) of circulating metabolites have revealed the role of genetic regulation on the human metabolome. Most previous investigations focused on European ancestry, and few studies have been conducted among populations of African descent living in Africa, where the infectious disease burden is high (e.g., human immunodeficiency virus (HIV)). It is important to understand the genetic associations of the metabolome in diverse at-risk populations including people with HIV (PWH) living in Africa. After a thorough literature review, the reported significant gene-metabolite associations were tested among 490 PWH in South Africa. Linear regression was used to test associations between the candidate metabolites and genetic variants. GWAS of 154 plasma metabolites were performed to identify novel genetic associations. Among the 29 gene-metabolite associations identified in the literature, we replicated 10 in South Africans with HIV. The UGT1A cluster was associated with plasma levels of biliverdin and bilirubin; SLC16A9 and CPS1 were associated with carnitine and creatine, respectively. We also identified 22 genetic associations with metabolites using a genome-wide significance threshold (p-value < 5 × 10^-8). In a GWAS of plasma metabolites in South African PWH, we replicated reported genetic associations across ancestries, and identified novel genetic associations using a metabolomics approach.

SUBMITTER: Liu C

PROVIDER: S-EPMC9316179 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionPeople with HIV (PWH) are at increased risk for atherosclerotic cardiovascular disease (CVD). Screening for CVD risk factors is recommended but not routine in South African HIV clinics. We sought to describe the prevalence of CVD risk factors among antiretroviral treatment (ART)-experienced patients in South Africa.MethodsWe performed a prospective, observational cross-sectional study of PWH (>21 years, excluding pregnant women) on ART in South Africa. We interviewed patients regarding CVD risk factors, and obtained two blood pressure (BP) measurements and random/fasting glucose via a point-of-care glucometer. Standardized chart reviews provided individuals' HIV-specific data. We defined hypertension as: self-reported use of antihypertensives or mean systolic BP (SBP) ≥140 mmHg or diastolic BP (DBP) ≥90 mmHg (Stage 1) or SBP ≥160 mmHg or DBP ≥100 mmHg (Stage 2). We defined diabetes as self-reported use of insulin/oral hypoglycaemics or fasting (random) glucose ≥7.0 (≥11.1) mmol. We obtained risk ratios (RR) for hypertension from a multivariable log-binomial regression model, adjusting for age, sex and diabetes.ResultsFrom March 2015 to February 2016, 458 participants enrolled with median age 38 years (interquartile range (IQR) 33 to 44 years) and median CD4 466/μL (IQR 317 to 638/μL); 78% were women. Participants were on ART for a median of four years, with 33% on ART ≥6 years. Almost a quarter (106/458) met the study definition for hypertension, of whom 45/106 (42%) were previously diagnosed, 23/45 (51%) were on medication and 4/23 (17%) were controlled. Eight participants had asymptomatic hypertensive urgency (BP≥180/110 mmHg). Of the 458 participants, 26 (6%) met the study definition for diabetes, half of whom (13/26) were already diagnosed; 11/13 (85%) were on treatment, of whom 4/11 (36%) had normal glucose. Age was the only significant predictor of hypertension (RR, 1.04; 95% CI, 1.03 to 1.06, p < 0.0001) in the multivariable model.ConclusionsHypertension and diabetes were prevalent among PWH prescribed ART in South Africa with less than half diagnosed, and still fewer treated and controlled. Hypertension was independently associated with age but not with HIV-specific factors. Screening for and treatment of CVD risk factors could decrease future morbidity and mortality, especially as this population ages.

Project description:BackgroundStudies from high income countries report that HIV-positive people have an impaired systolic and diastolic cardiac function compared to HIV-negative people. It is unclear if results can be translated directly to the Sub-Saharan Africa context. This study assesses electro- and echocardiographic characteristics in an urban African population, comparing HIV-positive people (treated and not yet treated) with HIV-negative controls.MethodsWe conducted a cross-sectional study in Johannesburg, South Africa. We enrolled HIV-positive participants from three randomized controlled trials that had recruited participants from routine HIV testing programs. HIV-negative controls were recruited from the community. Data were collected on demographics, cardiovascular risk factors, medical history and electrocardiographic and echocardiographic characteristics.ResultsIn total, 394 HIV-positive participants and 153 controls were enrolled. The mean age of HIV-positive participants was 40±9 years (controls: 35±10 years), and 34% were male (controls: 50%). Of HIV-positive participants 36% were overweight or obese (controls: 44%), 23% had hypertension (controls: 28%) and 12% were current smoker (controls: 37%). Median time since HIV diagnosis was 6.0 years (IQR 2.3-10.0) and median treatment duration was 4.0 years (IQR 0.0-8.0), 50% had undetectable viral load. The frequency of anatomical cardiac abnormalities was low and did not differ between people with and without HIV. We observed no relation between HIV or anti-retroviral therapy (ART) and systolic or diastolic heart function. There was an association between ART use and corrected QT interval: +11.8 ms compared to HIV-negative controls (p<0.01) and +18.9 ms compared to ART-naïve participants (p = 0.01). We also observed a higher left ventricular mass index in participants on ART (+7.8 g/m2, p<0.01), but this association disappeared after adjusting for CD4 cell count, viral load and HIV-duration.ConclusionThe low number of major cardiac abnormalities in this relatively young, well managed urban African HIV-positive population is reassuring. The increase in corrected QT interval and left ventricular mass may contribute to higher cardiac mortality and morbidity in people living with HIV in the long term.

Project description:BackgroundHIV treatment has reduced morbidity and mortality. By 2012, it was estimated that 60.4% of eligible South Africans accessed antiretroviral treatment; however, treatment adherence and retention remain the greatest challenges. There is a growing belief that social capital, seen as "the features of social organization that facilitate cooperation for mutual benefit", is important in promoting HIV treatment retention. The aim of this study was to establish whether social capital is associated with HIV treatment outcomes.Methods and findingsThis was a cross-sectional analysis of data from a cohort study that investigated how patient outcomes were linked to clinical characteristics, and included exploratory factor and logistic regression analysis. Data from 943 patients were analyzed. Outcomes for the analysis were visit non-adherence, unsuppressed viral load, and treatment failure. Sixteen percent of patients (n = 118) had unsuppressed viral loads; 19% (n = 179) were non-adherent; and 32% (n = 302) experienced treatment failure. Social capital had two dimensions that were described by two factors. There was no association between either factor and visit non-adherence. Social capital factor 1 was marginally associated with lower risks of unsuppressed viral load and treatment failure at 12 months (OR = 0.78; 95% CI = 0.58-1.03 and OR = 0.76; 95% CI = 0.62-0.93, respectively); but not with visit non-adherence (OR = 0.93; 95% CI = 0.71-1.22). After controlling for confounders, the odds of both unsuppressed viral load and treatment failure decreased with an increase in social capital factor 1.ConclusionThis study suggests that social capital, in terms of the number of groups to which an HIV-infected person belongs, the diversity of the groups, availability of child support, and time available for community projects, is protective against poor HIV treatment outcomes. Implementers and policy makers in the areas of HIV treatment and prevention need to consider the inclusion of social capital in the design of HIV/AIDS treatment program.

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Crosstalk between Host Genome and Metabolome among People with HIV in South Africa.

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