673   Long-Term Efficacy and Tolerance of Switching the Protease Inhibitor for Non- Nucleoside Reverse Transcriptase Inhibitors: A 52- Week, Multicenter, Prospective Study.

. J. L. Casado*¹, J. Arrizabalaga², A. Antela¹, J. A. Iribarren², A. Moreno¹, F. Dronda¹, M. J. Perez-Elias¹, and S. Moreno¹for the BEGIN Study .
¹Ramon y Cajal Hosp., Madrid and²Ntra. Sra de Aranzazu Hosp., San Sebastian, Spain.

Background:Simplification strategies reducing the number of drugs have not been effective in continuing viral suppression. We explored the role of non-nucleoside reverse transcriptase inhibitors (NNRTIs) as maintenance therapy for HIV-1-infected patients who developed PI intolerance or toxicity despite viral suppression.

Methods:One hundred patients receiving PI therapy for a median time of 19 months (range 4—39) and with a HIV load <50 copies/ml were included in a prospective, non-randomized study of triple therapy with 2 NRTIs and nevirapine (68) or efavirenz (32).

Results:Median CD4⁺count was 489 cells/mm³(123—1208), and patients were below 50 copies/ml for a median time of 12 months (1—36), despite extensive prior treatment with nucleoside analogues (NRTIs) in 76% of cases for a median time of 33 months (3—108). After 12 months of follow-up, 73% of patients in the intention- to-treat analysis (missing = failure) and 80% in the as-treated analysis persisted below 50 copies/ml, and CD4⁺count increased to 567 cells/mm³. Twenty-seven patients developed toxicity on NNRTI therapy, mainly CNS symptoms with efavirenz (23%) or rash and hepatitis with nevirapine (6 and 8%, respectively). However, grade 3-4 side effects were observed only in 6% of patients. Mean cholesterol (from 241 to 206 mg/dL; p < 0.001) and triglycerides plasma values (from 286 to 194 mg/dL; p < 0.001) decreased significantly without subjective changes in lipoatrophy. Simplification failure was observed especially in patients pretreated with NRTIs (17 vs. 8%, p = 0.13), and genotypic testing showed the predominant presence of mutations at residues 184 and 215 in failing patients.

Conclusions:A NNRTI-based triple therapy is effective in maintaining viral suppression for patients who change PI therapy, with improvement of lipidic abnormalities but not of lipoatrophy. However, those patients pretreated with NRTIs have a higher risk of failure due to preexisting resistance.