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Is There Sufficient Evidence for a Causal Association between Antiretroviral Therapy and Diabetes in HIV-infected Patients? A Meta-analysis.


The association of antiretroviral therapy (ART) with diabetes is inconsistent and varies widely across primary epidemiological studies. A comprehensive and more precise estimate of this association is fundamental to establishing a plausible causal link between ART and diabetes.We identified epidemiological studies that compared mean fasting plasma glucose (FPG) concentrations and proportions of diabetes and metabolic syndrome between HIV-infected patients naïve and exposed to ART. Mean difference (MD) in FPG concentrations and odds ratios (OR) of diabetes and metabolic syndrome were pooled using random-effects meta-analyses.Data on 20,178 participants from 41 observational studies were included in the meta-analyses. Mean FPG concentrations (Pooled MD: 4.66 mg/dl, 95% confidence interval [CI] 2.52 to 6.80, 24 studies) and the odds of diabetes (Pooled OR: 3.85, 95% CI 2.93 to 5.07, 10 studies) and metabolic syndrome (Pooled OR: 1.45, 95% CI 1.03 to 2.03, 18 studies) were significantly higher among ART-exposed patients, compared to their naïve counterparts. ART was also associated with significant increases in FPG levels in studies with mean ART duration ≥ 18 months (Pooled MD: 4.97 mg/dl, 95% CI 3.10 to 6.84, 14 studies), but not in studies with mean ART duration < 18 months (Pooled MD: 4.40 mg/dl, 95% CI -0.59 to 9.38, 7 studies).ART may potentially be the single most consistent determinant of diabetes in people living with HIV worldwide. However, given the preponderance of cross-sectional studies in the meta-analysis, the association between ART and diabetes cannot be interpreted as cause and effect.