Risk of lipodystrophy in HIV-1-infected patients treated with protease inhibitors: a prospective cohort study

Background Risk factors for lipodystrophy in patients infected with HIV-1 t reated with highly active antiretroviral therapy (HAART) containing HIV-1 p rotease inhibitors are poorly understood. We aimed to identify the risk fac tors for lipodystrophy in antiretroviral-naive HIV-1-infected adults on HAA RT. Methods Moderate or severe body-fat changes were clinically assessed and ca tegorised as subcutaneous lipoatrophy, central obesity, or both, in all con secutive antiretroviral-naive HIV-1-infected adults who began HAART with tw o nucleoside reverse transcriptase inhibitors plus at least one protease in hibitor from October, 1996, to September, 1999. A person-years analysis was used to calculate the incidence of types of lipodystrophy, and Cox proport ional hazards models were used to describe the univariate and multivariate factors associated with progression to any lipodystrophy. Findings After a median follow-up of 18 months, 85 (17%) of the 494 patient s developed some type of lipodystrophy. The incidences of any lipodystrophy , lipodystrophy with subcutaneous lipoatrophy, and lipodystrophy with centr al obesity were 11.7 (95% CI 9.2-14.2), 9.2 (7.0-11.4), and 7.7 (5.7-9.7) p er 100 patient-years. An increased risk for any lipodystrophy was found amo ng women as compared with men (relative hazard 1.87 [1.07-3.28]), heterosex uals (2.86 [1.50-5.48]), and homosexuals (2.17 [1.07-4.42]) as compared wit h intravenous drug users, with increasing age (1.33 per 10 years older [1.0 8-1.62]), and with the duration of exposure to antiretroviral therapy (1.57 per 6 months extra [1.30-1.88]) but not with any individual antiretroviral agent. The factors associated with an increased risk for lipodystrophy wit h subcutaneous lipoatrophy or lipodystrophy with central obesity were very similar to those associated with any lipodystrophy. The duration of indinav ir use may represent an additional contribution for the development of lipo dystrophy with central obesity (1.26 per 6 months extra [0.99-1.60]); p=0.0 64). Interpretation Risk factors associated with development of any lipodystroph y, lipodystrophy with subcutaneous lipoatrophy, and tipodystrophy with cent ral obesity in patients infected with HIV-1 who were receiving HAART contai ning protease inhibitors are multifactorial and overlapping, and cannot be exclusively ascribed to the duration of exposure to an particular antiretro viral agent.