Metabolic Effects of Initial PI-Sparing Antiretroviral Therapy

Initial reports of metabolic dysfunction among HIV-infected patients on potent combination antiretroviral therapy focused on the role of PIs, but later reports described a more complex situation, with NRTIs and NNRTIs also having metabolic effects. Now, investigators have analyzed data from ACTG 5095 to determine the metabolic aspects of three initial PI-sparing regimens: AZT/3TC/abacavir, efavirenz + AZT/3TC, and efavirenz + AZT/3TC/abacavir. Previous results from this large trial demonstrated the superiority of efavirenz-containing regimens over triple-nucleoside regimens (ACC Jun 1 2004) and showed that adding abacavir to efavirenz + AZT/3TC offered no virologic benefit (ACC Sep 11 2006). Fasting blood samples were obtained at baseline and every 24 weeks for approximately 2 years. Age- and gender-adjusted mean lipid values were compared with U.S. population norms based on 1999–2002 National Health and Nutrition Examination Survey (NHANES) data.

During the first 24 weeks, the treatment groups all had similar modest increases in glucose levels and decreases in insulin sensitivity. The two groups receiving efavirenz-based regimens had significantly greater increases in all lipid parameters (total, LDL, and HDL cholesterol and triglycerides) than did the AZT/3TC/abacavir group, but the increases were still relatively modest.

Prior to treatment initiation, the study population had a smaller percentage of people meeting criteria for the metabolic syndrome than did the NHANES cohort. However, after 96 weeks of antiretroviral therapy, values for hypertension, glucose intolerance, low HDL cholesterol, and abdominal obesity tended to “normalize,” and the percentage of patients meeting criteria for the metabolic syndrome became similar to that in the general population. Adjusted mean triglyceride levels were significantly higher at week 96 in the study population than in the NHANES cohort, whereas adjusted mean total, HDL, and LDL cholesterol levels were significantly lower.