Risks and benefits of replacing protease inhibitors by nevirapine in HIV-infected subjects under long-term successful triple combination therapy

Objective: To analyse the safety and efficacy of replacing the protease inh ibitor (PI) by nevirapine (NVP) in subjects experiencing a long-term contro l of virus replication under a triple PI-containing antiretroviral combinat ion. Design: Prospective evaluation of 138 HIV-positive subjects with plasma vir al load below 50 HIV-RNA copies/ml for the last 6 months under a triple PI- containing regimen, who were randomly assigned to either replace the PI by NVP (n = 104) or continue on the same treatment (n = 34). Methods: Viral load, CD4 count, lipid profile, body-shape features, and qua lity of life parameters were all assessed at the time of randomization and every 3 months thereafter. Results: In an intent-to-treat analysis, a rebound in viral load occurred i n 11% of subjects during the first 6 months after replacing the PI by NVP, whereas it appeared in 29% of those who remained on PI (P = 0.007). Treatme nt failure was related to lack of adherence in 90% of subjects on PI, but o nly in 22% of those receiving NVP (P = 0.006). The CD4 cell count outcome d id not differ significantly comparing both groups at 6 months, although in patients receiving NVP an average reduction of 35 x 10(6) cells/l was obser ved, whereas in those on PI a positive trend was still recorded (+54 x 10(6 ) cells/l). At the time of randomization, 77.5 and 57.5% of subjects had ch olesterol and triglyceride values above 200 mg/dl, respectively. No signifi cant changes in the lipid profile were observed in any of the groups therea fter. Body-shape abnormalities were recorded in 70% of persons at the time of randomization, and partially reversed at 6 months in 50% of subjects who replaced the PI by NVP. A quality of life score recorded a significant imp rovement in subjects who switched to NVP compared with those who continued on PI. Conclusions: The replacement of PI by NVP seems to be safe both virological ly and immunologically, provides a significant improvement in the quality o f life and in half of patients ameliorate lipodystrophic body-shape changes at 6 months, although serum lipid abnormalities still remain unmodified, ( C) 2000 Lippincott Williams & Wilkins.