Effect of Nonnucleoside Reverse Transcriptase Inhibitor-based Antiretroviral Therapy on Dysglycemia and Insulin Sensitivity in South African HIV-infected Patients

Background: Data on the prevalence of the complications of antiretroviral therapy (ART) (diabetes, central fat accumulation, peripheral fat wasting, and dyslipidemia) in sub-Saharan Africa are sparse. We examined the prevalence and associated risk factors of dysglycemia and insulin sensitivity in HIV-infected South Africans.

Methods: HIV-infected patients, on nonnucleoside reverse transcriptase inhibitor-based ART or ART-naive, had oral glucose tolerance tests and clinical anthropometry. Insulin sensitivity and β-cell function were assessed.

Results: The prevalence of dysglycemia in 406 ART-naive patients and 443 patients on ART was 25.7% and 21.9% (P = 0.193), respectively. Dysglycemic patients on ART had a similar body mass index (P = 0.440), greater waist circumference (P = 0.047), and smaller calf skinfold thickness (P = 0.015) than dysglycemic ART-naive patients but no difference in β-cell function or insulin sensitivity. Normoglycemic patients on ART had a greater body mass index (P = 0.0009), waist circumference (P = 0.0001), and abdominal skinfold thickness (P = 0.040), similar calf skinfold thickness (P = 0.079), and reduced β-cell function [lower insulinogenic index (P = 0.027) and oral disposition index (D(o), P = 0.020)] compared with normoglycemic ART-naive patients. In multivariate analysis, older age [odds ratio (OR): 1.04, 95% confidence interval (CI): 1.02 to 1.06], male gender (OR: 1.96, 95% CI: 1.28 to 2.99), higher CD4 count (OR: 1.0, 95% CI: 1.00 to 1.02) and use of efavirenz (OR: 1.70, 95% CI: 1.19 to 2.45) were associated with dysglycemia.

Conclusions: The prevalence of dysglycemia in ART-naive and ART patients was similar. Peripheral fat wasting was more common in dysglycemic patients on ART. The association of efavirenz with dysglycemia is important because first-line ART regimens in the developing world include nonnucleoside reverse transcriptase inhibitors, and increasingly, efavirenz is selected because of its perceived lower toxicity than nevirapine.