Metabolic syndrome in Zambian adults with human immunodeficiency virus on antiretroviral therapy

Abstract

Metabolic syndrome (MetS) is a constellation of factors including hypertension, abdominal obesity, dyslipidemia, and insulin resistance that separately and together significantly increase risk for cardiovascular disease (CVD) and diabetes. In sub-Saharan Africa, with a substantial burden of human immunodeficiency virus (HIV) and increasing prevalence of CVD and diabetes, there is a paucity of epidemiological data on demographic, laboratory, and clinical characteristics associated with MetS among people with HIV (people with human [PWH]). Therefore, this study aimed to determine the burden and factors influencing MetS in antiretroviral therapy (ART)-experienced individuals in Zambia. We collected cross-sectional demographic, lifestyle, anthropometric, clinical, and laboratory data in a cohort of ART-experienced (on ART for ≥6 months) adults in 24 urban HIV treatment clinics of Zambia between August, 2016 and May, 2020. MetS was defined as having ≥3 of the following characteristics: low high density lipoprotein cholesterol (HDL-c) (<1.0 mmol/L for men, <1.3 for women), elevated waist circumference (≥94 cm for men, ≥80 cm for women), elevated triglycerides (≥1.7 mmol/L), elevated fasting blood glucose (≥5.6 mmol/L), and elevated blood pressure (BP) (systolic BP ≥130 or diastolic BP ≥85 mm Hg). Virological failure (VF) was defined as HIV viral load ≥1000 copies/mL. The following statistical methods were used: Chi-square test, Wilcoxon rank-sum test, and multivariable logistic regression. Among 1108 participants, the median age (interquartile range [IQR]) was 41 years (34, 49); 666 (60.1%) were females. The prevalence of MetS was 26.3% (95% confidence interval [CI] 23.9–29.1). Age (adjusted odds ratio [OR] 1.07; 95% CI 1.04–1.11), female sex (OR 3.02; 95% CI 1.55–5.91), VF (OR 1.98; 95% CI 1.01–3.87), dolutegravir (DTG)-based regimen (OR 2.10; 95% CI 1.05–4.20), hip-circumference (OR 1.03; 95% CI 1.01–1.05), T-lymphocyte count (OR 2.23; 95% CI 1.44–3.43), high-sensitivity C-reactive protein (hsCRP) (OR 1.14; 95% CI 1.01–1.29), and fasting insulin (OR 1.02; 95% CI 1.01–1.04) were significantly associated with MetS. Metabolic syndrome was highly prevalent among HIV+ adults receiving ART in Zambia and associated with demographic, clinical, anthropometric, and inflammatory characteristics. The association between MetS and dolutegravir requires further investigation, as does elucidation of the impact of MetS on ART outcomes in sub-Saharan African PWH.

Determinants of Dyslipidemia in Africa: A Systematic Review and Meta-Analysis

“…Moreover, this study also found that lower odds of dyslipidemia were found among participants who have attained a lower level of education when compared with those who attended college and above. This is in agreement with other studies ( 41 , 73 ). In contrast, other studies found contradicting results ( 74 , 75 ).…”

Metabolic syndrome in people with HIV from Guatemala: analysis of components and risk factors

“…35 INSTI have been linked through numerous studies to undesired weight gain, BMI increase 36 and metabolic syndrome. 37 INSTI use in our study was low (<10%) but this is likely to increase sharply due to this update in treatment guidelines, which could potentially change BMI trends and metabolic syndrome prevalence in PWH. Age was another factor significantly associated to metabolic syndrome in our study.…”

The risk of hyperglycemia associated with use of dolutegravir among adults living with HIV in Kampala, Uganda: A case-control study

“…ART = antiretroviral treatment; BMI = body mass index; DTG = Dolutegravir metabolism. [18][19][20][21]26,27 The mechanism by which DTG causes deranged glucose metabolism is not well understood, although it is hypothesized that DTG causes insulin resistance by chelating magnesium ions which are needed as cofactors for effective action of insulin. 28 Our findings indicate that PLHIV who had previously been prescribed DTG-based ART had seven times greater odds of having hyperglycemia compared to those who had been previously prescribed non-DTG ART regimens, even after controlling for potential confounders such as age, BMI, and hypertension as a co-morbidity.…”

“…[17][18][19][20] A more recent crosssectional study conducted in Zambia found that when compared to NNRTI's, DTG-based ART was associated with double the risk of developing metabolic syndrome among PLHIV; metabolic syndrome consists of hyperglycemia, hypertension, and dyslipidemia among other parameters all of which are known to increase the risk of DM. 21 In Uganda and throughout SSA, where DTG is being widely rolled out and there is an increasing burden of NCDs among PLHIV and the general population, there is a paucity of information on the association between use of DTGbased ART and hyperglycemia. 4 Those who develop hyperglycemia following use of DTG-based ART may need to be considered for alternate ART regimens, such as NNRTIbased which are better tolerated in this regard.…”

“…In multivariable analysis, patients with prior DTG use had seven times greater odds of subsequent diagnosis of hyperglycemia compared to those who had non-DTG-based regimens (adjusted odds ratio [aOR] 7.01, 95% CI 1.96-25.09). The odds of hyperglycemia also increased with age (56 years and above vs. [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] aOR 12.38,) and hypertension (aOR 5.78,). Our study demonstrates a strong association between prior DTG exposure and subsequent diagnosis of hyperglycemia.…”