We prospectively followed 20 consecutive patients with human immunodeficiency virus type 1 (HIV-1) with viral loads of <200 RNA copies/mL. These patients had been treated with 2 nucleoside reverse transcriptase inhibitors and <greater than or equal to>1 HIV-1 protease inhibitor for greater than or equal to3 months; they developed body changes consistent with lipodystrophy and requested they be switched from protease inhibitor to efavirenz, At baseline and every 3 months, we assessed the following: body mass index, waist-to-hip ratio, regional fat thickness (assessed by sonography), fasting total and high-density lipoprotein cholesterol, triglycerides, glucose, insulin, CD4(+) cells, and viral load. At baseline, hypertriglyceridemia (greater than or equal to 200 mg/dL) was present in 17 (85%) patients, hypercholesterolemia (greater than or equal to 200 mg/dL) in 14 (70%), and impaired fasting glucose (greater than or equal to 110 mg/dL) in 8 (40%); CD4(+) T cells were 280 X 10(6) cells/L (range, 64-942 X 10(6) cells/L). HIV-1 RNA had been at <200 copies/mL for a median of 14 months (range, 3-24 months). Six months after switching to efavirenz, there was a reduction in triglyceride levels (a decrease of 31%; P = .03) and fasting insulin resistance index Ca decrease of 28%; P = .03), but total and high-density lipoprotein cholesterol and glucose did not change. Waist-to-hip ratio decreased from 0.92 to 0.87 (P = .06). Subcutaneous fat thickness did not change. CD4(+) cells remained stable (363 x 10(6) cells/L; range, 102-741 X 10(6) cells/L; P = .65). Nineteen patients (95%) had HIV-1 RNA levels that remained at <200 copies/mL. Although CD4+ response and viral suppression remained preserved after 6 months of switching from protease inhibitor to efavirenz, the benefits of this approach on the evolution of lipodystrophy were limited, and our findings do not support its routine recommendation to treat lipodystrophy.