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This study examined the associations between tobacco smoking and serum cotinine levels, an objective biochemical measure of tobacco smoke exposure, with markers of inflammation, i.e., interferon-gamma (IFN-γ), interleukin 10 (IL-10), interleukin 2 (IL-2) and tumour necrosis factor-alpha (TNF-α) in people living with HIV (PLWH).These specific markers were selected because of their hypothesised associations with smoking, PLWH and their outcomes. In a random sample of ≥ 18-year-old PLWH receiving care at 17 public healthcare facilities across the Western Cape Province in South Africa, data collection included self-reported smoking history, and serum levels of cotinine and selected inflammatory markers. The inflammatory marker data were log transformed because of the skewedness of their distribution. Linear regression models (1) adjusted for age and gender, and (2) fully adjusted for age, gender, current alcohol use, body mass index and CD4 counts were used to examine the associations between smoking tobacco or serum cotinine and inflammatory markers. Level of significance was p < 0.05. Among 749 PLWH who were mainly women (79%), the mean age was 38.5 (8.9) years and similar when stratified by smoking status. Serum cotinine levels exhibited a striking discrepancy, with a median of 154 ng/mL among current smokers, in stark contrast to the consistent median values of 10 ng/mL observed among past and never smokers. In regression models adjusted for age and gender, current smoking and frequent smoking were associated with lower IL-2 but higher TNF-α. Log-cotinine exhibited associations with IFN-γ, IL-10, and TNF-α, while cotinine levels ≥ 10 ng/mL compared to < 10 ng/mL were associated with higher IFN-γ and TNF-α. In fully adjusted models, log-cotinine and cotinine levels ≥ 10 ng/mL displayed significant associations with higher IFN-γ and lower IL-2. This study underscores the importance of investigating the interplay between smoking tobacco or serum cotinine levels with pro-inflammatory cytokines in PLWH. It signals the need for comprehensive research to unravel the potential synergistic impacts of smoking tobacco and HIV infection on chronic inflammation and immune dysregulation, shedding light on critical avenues for intervention and management strategies., (© 2024. The Author(s).)

Introduction: In people living with human immunodeficiency virus (PLHIV), traditional cardiovascular risk factors, exposure to HIV per se and antiretroviral therapy (ART) are assumed to contribute to cardiometabolic diseases. Nevertheless, controversy exists on the relationship of HIV and ART with diabetes. To clarify the relationship between HIV and type 2 diabetes, this review determined, in PLHIV in Africa, diabetes and prediabetes prevalence, and the extent to which their relationship was modified by socio-demographic characteristics, body mass index (BMI), diagnostic definitions used for diabetes and prediabetes, and HIV-related characteristics, including CD4 count, and use and duration of ART., Methods: For this systematic review and meta-analysis (PROSPERO registration CRD42021231547), a comprehensive search of major databases (PubMed-MEDLINE, Scopus, Web of Science, Google Scholar and WHO Global Health Library) was conducted. Original research articles published between 2000 and 2021 in English and French were included, irrespective of study design, data collection techniques and diagnostic definitions used. Observational studies comprising at least 30 PLHIV and reporting on diabetes and/or prediabetes prevalence in Africa were included. Study-specific estimates were pooled using random effects models to generate the overall prevalence for each diagnostic definition. Data analyses used R statistical software and "meta" package., Results: Of the 2614 records initially screened, 366 full-text articles were assessed for eligibility and 61 were selected. In the systematic review, all studies were cross-sectional by design and clinic-based, except for five population-based studies. Across studies included in the meta-analysis, the proportion of men was 16-84%. Mean/median age was 30-62 years. Among 86,412 and 7976 participants, diabetes and prediabetes prevalence rates were 5.1% (95% CI: 4.3-5.9) and 15.1% (9.7-21.5). Self-reported diabetes (3.5%) was lower than when combined with biochemical assessments (6.2%; 7.2%)., Discussion: While not statistically significant, diabetes and prediabetes were higher with greater BMI, in older participants, urban residents and more recent publications. Diabetes and prediabetes were not significantly different by HIV-related factors, including CD4 count and ART., Conclusions: Although HIV-related factors did not modify prevalence, the diabetes burden in African PLHIV was considerable with suboptimal detection, and likely influenced by traditional risk factors. Furthermore, high prediabetes prevalence foreshadows substantial increases in future diabetes in African PLHIV., (© 2023 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: Gamma-glutamyl transferase (GGT) has recently been reported as a biomarker for cardiovascular (CVD) risk in general populations. We investigated the associations of GGT with cardio-metabolic diseases and CVD risk in South Africans living with HIV., Methods: In this cross-sectional study, HIV-infected adults were randomly recruited across 17 HIV clinics in the Western Cape Province. Homeostatic model assessment for insulin resistance (HOMA-IR), hypertension, diabetes, metabolic syndrome by Joint Interim Statement criteria (JIS-MS), a ≥5% and ≥10% predicted risk for a CVD event within 10 years by the Framingham risk score (10-years-CVD risk) were computed. Associations between GGT and cardio-metabolic trait were explored using linear and binomial logistic regressions adjusted for age, gender, lifestyle behaviours and HIV-related characteristics., Results: Among 709 participants (561 women, mean age 38.6 years), log-GGT was positively associated with waist circumference (β=2.75; p<0.001), diastolic blood pressure (β=1.65; p=0.006), total cholesterol (β=0.21; p<0.001), low-density lipoprotein-cholesterol (β=0.16; p<0.001), high-density lipoprotein-cholesterol and log-triglycerides (both β=0.12; p<0.001), fasting plasma glucose (β=0.19; p=0.031), 2-hour-post-glucose-load plasma glucose (β=0.26; p=0.007), HOMA-IR (β=0.13; p=0.001), log-high-sensitivity C-reactive-protein (β=0.3; p<0.001) in linear regression analyses; with hypertension [OR=1.41 (95%CI, 1.13-1.75); p=0.001], JIS-MS [OR=1.33 (1.05-1.68); p=0.016], ≥5% 10-year-CVD risk [OR=1.55 (1.24-1.9400); p<0.001] and ≥10% 10-year-CVD risk [OR=1.56 (1.08-2.23); p=0.016] but not with diabetes [OR=1.24 (0.88-1.71), p=0.205] in logistic regression analyses., Conclusions: In this study, GGT levels were associated with cardio-metabolic variables independent of HIV specific attributes. If confirmed in longitudinal studies, GGT evaluation maybe included in CVD risk monitoring strategies in people living with HIV., Competing Interests: The authors have declared that no competing interests exist.

Background: Glycated haemoglobin (HbA1c) test has been increasingly promoted as an alternative to fasting plasma glucose (FPG) or oral glucose tolerance test (OGTT) to diagnose dysglycaemia but its performance in HIV-infected Africans has yet to be established. This study aimed to assess the diagnostic accuracy of HbA1c for dysglycaemia including FPG-defined and OGTT-defined dysglycaemia, and OGTT-defined diabetes in HIV-infected Africans, and the effect of HbA1c-predicted dysglycaemia on Joint Interim Statement (JIS)-based prevalent metabolic syndrome (MS)., Methods: A cross-sectional study included HIV-positive patients recruited across public healthcare facilities in the Western Cape. The recommended HbA1c cut-points were tested alongside the optimal cut-points obtained from receiver operating characteristic curve analyses, while the agreement between the MS criteria were assessed using kappa statistic., Results: 748 participants (157 men), median age 38 years, 93% on anti-retroviral drugs were included. The optimal HbA1c cut-points of 5.75% (39.3 mmol/mol) showed 54% sensitivity, 84% specificity for FPG-defined dysglycaemia, and 52% sensitivity, 85% specificity for OGTT-defined dysglycaemia. The HbA1c value of 5.85% (40.4 mmol/mol) (63% sensitivity, 99% specificity) was optimal for diabetes. The internationally advocated cut-point of 6.5% (48 mmol/mol) had 37% sensitivity and 99% specificity for diabetes, while HbA1c ≥5.7% (≥39 mmol/mol) yielded similar performance with the study-specific cut-point for any dysglycaemia. MS prevalence by the JIS criteria (28.2%) increased to 29.7% when using HbA1c ≥5.75% (≥39.3 mmol/mol) and to 32.9% with HbA1c ≥5.7% (≥39 mmol/mol); agreement between the original and modified criteria was generally good., Conclusions: This study agrees with the internationally recommended HbA1c cut-point for detecting dysglycaemia, but not for diabetes in HIV-infected Africans. In line with previous studies in general African populations, our findings suggest that similar factors interfere with HbA1c values regardless of HIV infection status. Replacing FPG-based with HbA1c-predicted dysglycaemia in the JIS criteria to diagnose MS is feasible in HIV-infected Africans., Competing Interests: EJM is employed by Global Evaluation Science. There are no patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all PLOS ONE policies on sharing data and materials.

Background: The applicability of the internationally advocated cut-off points of waist circumference (WC) derived from Caucasians to diagnose metabolic syndrome (MS) in HIV-infected Africans is unknown. This study aimed to determine the optimal WC cutoffs for MS diagnosis in HIV-infected people receiving care at public healthcare facilities in the Western Cape Province in South Africa., Methods: Data from 748 randomly selected participants (591 women), with a median age of 38 years, were analysed. The Youden's index and the top-left-point approaches were used to determine the optimal cutoffs of WC for predicting ≥2 non-adipose MS components., Results: The two approaches generated the same WC cut-off point in women, 92 cm (sensitivity 64%, specificity 64%) but different cut-off points in men: 87 cm (sensitivity 48%, specificity 85%) based on the Younden's index and 83 cm (sensitivity 59%, specificity 74%) by the top-left-point method. The advocated thresholds of 94 cm in men had low sensitivity (30%) but high specificity (92%) whereas 80 cm in women showed low specificity (32%) but high sensitivity (85%) for diagnosing MS in this sample. Most African-specific cut-off points performed well, with 90 cm providing acceptable performance in both men (sensitivity 43%, specificity 88%) and women (sensitivity 66%, specificity 59%)., Conclusions: This study underlines the sub-optimal performance of internationally recommended WC thresholds for MS diagnosis in HIV-infected Africans, and supports the need to revisit the guidelines on WC criterion in African population across the board. A single threshold of 90 cm for both genders would be a practical suggestion.

The distribution of body size phenotypes in people with human immunodeficiency virus (HIV) infection has yet to be characterized. We assessed the distribution of body size phenotypes overall, and according to antiretroviral therapy (ART), diagnosed duration of the infection and CD4 count in a sample of HIV infected people recruited across primary care facilities in the Western Cape Province, South Africa. Adults aged ≥ 18 years were consecutively recruited using random sampling procedures, and their cardio-metabolic profile were assessed during March 2014 and February 2015. They were classified across body mass index (BMI) categories as normal-weight (BMI < 25 kg/m²), overweight (25 ≤ BMI < 30 kg/m²), and obese (BMI ≥ 30 kg/m²), and further classified according to their metabolic status as "metabolically healthy" vs. "metabolically abnormal" if they had less than two vs. two or more of the following abnormalities: high blood glucose, raised blood pressure, raised triglycerides, and low HDL-cholesterol. Their cross-classification gave the following six phenotypes: normal-weight metabolically healthy (NWMH), normal-weight metabolically abnormal (NWMA), overweight metabolically healthy (OvMH), overweight metabolically abnormal (OvMA), obese metabolically healthy (OMH), and obese metabolically abnormal (OMA). Among the 748 participants included (median age 38 years (25th-75th percentiles: 32-44)), 79% were women. The median diagnosed duration of HIV was five years; the median CD4 count was 392 cells/mm³ and most participants were on ART. The overall distribution of body size phenotypes was the following: 31.7% (NWMH), 11.7% (NWMA), 13.4% (OvMH), 9.5% (OvMA), 18.6% (OMH), and 15.1% (OMA). The distribution of metabolic phenotypes across BMI levels did not differ significantly in men vs. women (p = 0.062), in participants below vs. those at or above median diagnosed duration of HIV infection (p = 0.897), in participants below vs. those at or above median CD4 count (p = 0.447), and by ART regimens (p = 0.205). In this relatively young sample of HIV-infected individuals, metabolically abnormal phenotypes are frequent across BMI categories. This highlights the importance of general measures targeting an overall improvement in cardiometabolic risk profile across the spectrum of BMI distribution in all adults with HIV.

Background: Cardio-metabolic risk factors are of increasing concern in HIV-infected individuals, particularly with the advent of antiretroviral therapy (ART) and the subsequent rise in longevity. However, the prevalence of cardio-metabolic abnormalities in this population and the differential contribution, if any, of HIV specific factors to their distribution, are poorly understood. Therefore, we conducted a systematic review and meta-analysis to estimate the global prevalence of metabolic syndrome (MS) in HIV-infected populations, its variation by the different diagnostic criteria, severity of HIV infection, ART used and other major predictive characteristics., Methods: We performed a comprehensive search on major databases for original research articles published between 1998 and 2015. The pooled overall prevalence as well as by specific groups and subgroups were computed using random effects models., Results: A total of 65 studies across five continents comprising 55094 HIV-infected participants aged 17-73 years (median age 41 years) were included in the final meta-analysis. The overall prevalence of MS according to the following criteria were: ATPIII-2001:16.7% (95%CI: 14.6-18.8), IDF-2005: 18% (95%CI: 14.0-22.4), ATPIII-2004-2005: 24.6% (95%CI: 20.6-28.8), Modified ATPIII-2005: 27.9% (95%CI: 6.7-56.5), JIS-2009: 29.6% (95%CI: 22.9-36.8), and EGIR: 31.3% (95%CI: 26.8-36.0). By some MS criteria, the prevalence was significantly higher in women than in men (IDF-2005: 23.2% vs. 13.4, p = 0.030), in ART compared to non-ART users (ATPIII-2001: 18.4% vs. 11.8%, p = 0.001), and varied significantly by participant age, duration of HIV diagnosis, severity of infection, non-nucleoside reverse transcriptase inhibitors (NNRTIs) use and date of study publication. Across criteria, there were significant differences in MS prevalence by sub-groups such as in men, the Americas, older publications, regional studies, younger adults, smokers, ART-naïve participants, NNRTIs users, participants with shorter duration of diagnosed infection and across the spectrum of HIV severity. Substantial heterogeneities across and within criteria were not fully explained by major study characteristics, while evidence of publication bias was marginal., Conclusions: The similar range of MS prevalence in the HIV-infected and general populations highlights the common drivers of this condition. Thus, cardio-metabolic assessments need to be routinely included in the holistic management of the HIV-infected individual. Management strategies recommended for MS in the general population will likely provide similar benefits in the HIV-infected.

Hypertension among HIV-positive populations has emerged as a new threat to the health and well being of people living with HIV, particularly among those receiving antiretroviral therapy. We reviewed the global evidence on the burden of disease (including prevalence and incidence), determinants of hypertension among HIV-positive populations, and the pharmacological management of hypertension in HIV-positive patients. We systematically searched PubMed-MEDLINE and EMBASE from January 2000 through February 2015 for relevant studies and traced their citations through the ISI Web of Science. We also searched the websites of the World Health Organisation, the International Society of Hypertension, and the International AIDS Society and constructed a narrative data synthesis. Hypertension is common in HIV-positive populations, with prevalence estimates ranging from 4.7 to 54.4% in high-income countries, and from 8.7 to 45.9% in low- and middle-income countries. The role of HIV-specific factors including disease severity, duration of disease, and treatments on the presence of hypertension in HIV-positive patients is reported, but patterns remain unclear. The clinical management of hypertension in HIV-positive patients is similar to those with hypertension in the general population; however, additional considerations should be given to potential drug interactions between antihypertensive agents and antiretroviral drugs to inform the clinician's selection of these therapies. Hypertension is common in HIV-positive populations and remains an important comorbidity affecting mortality outcomes. Further research examining the development of hypertension and its associated care in HIV-positive patients is required to optimize management of the dual conditions.