Body habitus changes and metabolic alterations in protease inhibitor-naive HIV-1-infected patients treated with two nucleoside reverse transcriptase inhibitors

Background: Cross-sectional and retrospective surveys suggest that nucleoside reverse transcriptase inhibitors (NRTIs) contribute to the metabolic and morphologic alterations observed in patients on antiretroviral therapy (ART). Objectives: To assess the risk of developing body habitus changes (BHCs) and metabolic abnormalities in protease inhibitor (PI)-naive HIV-1-infected patients treated with two NRTIs, and the risk associated with each of these drugs. Design: Prospective cohort study. Patients and Methods: The BHCs occurring in 335 patients treated with two NRTIs were evaluated every 3 months. The laboratory tests included determination of CD4 cell counts and the measurement of HIV RNA, serum glucose, cholesterol, and triglyceride levels. Cox proportional hazard models were used to describe the factors associated with the development of BHCs. Results: During a median exposure of 747.5 days, 46 patients (13.7%) developed BHCs: nine fat accumulation alone, 12 fat loss alone, and 25 combined fat loss and accumulation in different body regions. Fat loss alone occurred after a significantly longer median duration of treatment than the other two forms (p = .004). The risk of developing any BHC was significantly higher in female patients (p < .0001). Fat loss was the prevalent alteration in males. Hypertriglyceridemia was observed in 76 patients (22.7%), hypercholesterolemia in 35 (10.5%), and hyperglycemia in 48 (14.3%). The adjusted risk of developing hypertriglyceridemia was higher in the stavudine-treated patients (p = .04) and in those who had previously received ART (p = .02). The only independent factor associated with the development of hypercholesterolemia was to be ART experienced at baseline (p = .02), whereas age was associated with the development of hyperglycemia (p = .0096). Conclusions: Treatment with NRTIs may be responsible for the same morphologic alterations as those observed in patients treated with PIs. Moreover, altered triglyceride levels are also frequently observed. The different timing of presentation and gender distribution of BHCs suggest that multiple pathogenetic mechanisms are involved.