Ninety-six female and 92 male protease inhibitor (PI)-naïve patients on dual nucleoside reverse transcriptase inhibitor (NRTI) therapy were evaluated for alterations of fat tissue distribution. The patients -- who were excluded from the study if they had baseline fat redistribution, added a PI, or discontinued therapy -- were evaluated every 3 months. The authors, led by M. Galli, found that the patients showed unique fat tissue redistribution compared to redistribution characteristics frequently reported in PI-experienced patients. Specifically, PI-naïve patients showed fat wasting in the lower limbs and central adiposity with no overall weight change, while PI-experienced patients generally present with peripheral fat loss and limited central adiposity combined with overall weight reduction.

Women had a greater incidence of fat redistribution than men (26% versus 6%) Multivariate and univariate analyses of specific NRTI combinations suggests d4T + 3TC use was associated with greater risk of fat redistribution compared with AZT + 3TC use. Univariate evaluations of individual drugs indicated significant risks for d4T and 3TC relative to AZT; however, only d4T had significant associated risk when the data was assessed using multivariate analysis, compared to AZT. Gender and duration of NRTI therapy were also associated with increased risk. Additionally, d4T use correlated with increased triglyceride levels.

While the data suggest an association between d4T use and fat redistribution, the authors failed to provide baseline antiretroviral history, so the impact of previous NRTI therapy could not be determined. Additionally, baseline data on disease state were not reported, so these characteristics could not be analyzed. The study indicates that NRTI use is associated with fat redistribution, yet specific agents should not be implicated because of the lack of patient history and baseline characteristics.