BACKGROUND: Simpler and less toxic antiretroviral strategies are needed to maximize treatment compliance without sacrificing potency, at least for drug-experienced HIV-infected patients currently on regimens containing protease inhibitors (PIs). Small nonrandomized studies have suggested a beneficial role of PI-sparing regimens on lipodystrophy. OBJECTIVES: To assess the virologic, immunologic, and clinical benefit of switching the PI to nevirapine in patients with HIV-associated lipodystrophy and sustained viral suppression before entry in the study. DESIGN: Open-labeled, prospective, randomized, multicenter study. SETTING:Seven reference inpatient centers for HIV/AIDS in Spain. PATIENTS: One hundred six HIV-infected adults with clinically evident lipodystrophy who sustained HIV-RNA suppression for at least 6 months with PI-containing antiretroviral combinations. INTERVENTION: Replacement of the PI with nevirapine during 48 weeks (Group A) versus continuing the prior PI (Group B). MEASUREMENTS: Several virologic and immunologic analyses, standard and specific biochemical tests, and anthropometric and dual X-ray absorptiometry measurements. RESULTS: At week 48, an HIV-1 RNA level <400 copies/ml was maintained in 79% and 77% of patients in Groups A and B, respectively, whereas 74% and 72% of patients had viral load levels <50 copies/ml. Absolute CD4+ counts significantly increased in both groups compared with baseline values, and a significant decrease in CD38+CD8+ cells was observed in Group A (p <.01) but not in group B. Overall, no significant changes in anthropometric or body shape measurements were found after 48 weeks. Fasting total cholesterol and triglyceride levels decreased in Group A (but not in Group B) compared with baseline values (p <.05), although no significant differences were seen between groups at the end of the study. Subjects in Group A reported a better quality of life (QOL) index than controls (p <.001), with the main reason reported being the greater simplicity of the new drug regimen. CONCLUSIONS: Protease inhibitor-sparing regimens, including nevirapine, seem to be an effective alternative for PI-experienced patients. Nevirapine-based triple therapies allow maintained control of HIV-1 RNA levels and improve the immunologic response at 48 weeks of follow-up in patients with prior sustained virologic suppression. The switch to nevirapine significantly improved the lipidic profile in Group A, although there were no differences between groups at the end of the study. Additionally, no significant changes were seen in terms of lipodystrophy-related body shape changes 1 year after the PI substitution. Finally, nevirapine-containing regimens have a simpler dosing schedule, and this facilitates high adherence and improves QOL.
RCT Entities:
BACKGROUND: Simpler and less toxic antiretroviral strategies are needed to maximize treatment compliance without sacrificing potency, at least for drug-experienced HIV-infectedpatients currently on regimens containing protease inhibitors (PIs). Small nonrandomized studies have suggested a beneficial role of PI-sparing regimens on lipodystrophy. OBJECTIVES: To assess the virologic, immunologic, and clinical benefit of switching the PI to nevirapine in patients with HIV-associated lipodystrophy and sustained viral suppression before entry in the study. DESIGN: Open-labeled, prospective, randomized, multicenter study. SETTING: Seven reference inpatient centers for HIV/AIDS in Spain. PATIENTS: One hundred six HIV-infected adults with clinically evident lipodystrophy who sustained HIV-RNA suppression for at least 6 months with PI-containing antiretroviral combinations. INTERVENTION: Replacement of the PI with nevirapine during 48 weeks (Group A) versus continuing the prior PI (Group B). MEASUREMENTS: Several virologic and immunologic analyses, standard and specific biochemical tests, and anthropometric and dual X-ray absorptiometry measurements. RESULTS: At week 48, an HIV-1 RNA level <400 copies/ml was maintained in 79% and 77% of patients in Groups A and B, respectively, whereas 74% and 72% of patients had viral load levels <50 copies/ml. Absolute CD4+ counts significantly increased in both groups compared with baseline values, and a significant decrease in CD38+CD8+ cells was observed in Group A (p <.01) but not in group B. Overall, no significant changes in anthropometric or body shape measurements were found after 48 weeks. Fasting total cholesterol and triglyceride levels decreased in Group A (but not in Group B) compared with baseline values (p <.05), although no significant differences were seen between groups at the end of the study. Subjects in Group A reported a better quality of life (QOL) index than controls (p <.001), with the main reason reported being the greater simplicity of the new drug regimen. CONCLUSIONS: Protease inhibitor-sparing regimens, including nevirapine, seem to be an effective alternative for PI-experienced patients. Nevirapine-based triple therapies allow maintained control of HIV-1 RNA levels and improve the immunologic response at 48 weeks of follow-up in patients with prior sustained virologic suppression. The switch to nevirapine significantly improved the lipidic profile in Group A, although there were no differences between groups at the end of the study. Additionally, no significant changes were seen in terms of lipodystrophy-related body shape changes 1 year after the PI substitution. Finally, nevirapine-containing regimens have a simpler dosing schedule, and this facilitates high adherence and improves QOL.
Authors: Theodora E M S de Vries-Sluijs; Jeanne P Dieleman; Dennis Arts; Alwin D R Huitema; Jos H Beijnen; Martin Schutten; Marchina E van der Ende Journal: Clin Pharmacokinet Date: 2003 Impact factor: 6.447