Randomized, Controlled, 48-Week Study of Switching Stavudine and/or Protease Inhibitors to Combivir/Abacavir to Prevent or Reverse Lipoatrophy in HIV-Infected Patients

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Abstract
HIV-1 protease inhibitors (versus no protease inhibitors) and stavudine (versus zidovudine) are independently associated with a higher risk of lipoatrophy in HIV-infected patients. We sought to determine whether the revision of stavudine and/or protease inhibitor-containing regimens to combivir/abacavir would result in prevention and/or reversibility of lipoatrophy in HIV-1-infected patients. The investigation was a prospective, randomized, controlled, open-label study. The subjects included 37 HIV-1-infected individuals with stable undetectable HIV-1 loads who were taking a regimen containing either stavudine or zidovudine with lamivudine and a protease inhibitor. Subjects were randomized to continue therapy or switch stavudine to zidovudine and protease inhibitor to abacavir, such that the universal switch regimen was combivir (zidovudine/lamivudine) and abacavir. Total body, leg, and arm fat mass was measured at baseline, 24 weeks, and 48 weeks using whole-body dual-energy x-ray absorptiometry. Single-cut L4 computed tomography and assays of multiple metabolic parameters were also performed. There was an average gain in fat mass of 0.009 kg/(leg·mo) in switch patients versus a loss of 0.010 kg/(leg·mo) in controls (p = .04, on-treatment analysis) over 48 weeks. Significant arm fat restoration was observed in patients who switched regimens, with an average gain of 0.014 kg/(arm·mo) (p = .004), whereas controls did not have a significant change from baseline. Analyses of percentage changes in arm and leg fat masses showed similar findings. No significant effects on intra-abdominal fat, blood lipid levels, glycemic indices, and lactate levels were detected, although most baseline mean values were normal in study subjects. Combivir/abacavir maintained virological control in all but one case, and three (13.6%) of 22 individuals had adverse reactions to abacavir therapy. A switch to combivir/abacavir therapy was associated with objective evidence of limb fat-sparing and fat restoration compared with continued treatment with stavudine and/or protease inhibitor.