HIV-infected patients who take highly active anti-retroviral therapy (HAART) are at high risk for metabolic complications including insulin resistance, hypertriglyceridemia, and redistribution of body fat. As yet, there is no unifying hypothesis that explains these features, although the different drugs used (protease inhibitors in particular as well as nucleoside reverse transcriptase inhibitors) have emerged as primary suspects. There may also be a role for viral factors as well. We are examining the effect of viral proteins and drugs alone and in combination on a variety of adipose tissue functions, including differentiation, lipolysis, lipogenesis, and insulin-stimulated glucose uptake, in an attempt to deconvolute this complex and troublesome aspect of antiretroviral therapy.