Discontinuation of protease inhibitors due to intolerance: a longitudinal study in 309 HIV-1 positive patients

OBJECTIVES: Determine the frequency and nature of interruptions in HIV-1 pr otease inhibitor treatment in HIV-infected patients. PATIENTS AND METHODS: A longitudinal study included patients treated with a ntiretroviral protocols including at least one antiprotease and followed fr om 1 March 1996 through 1 March 1998. RESULTS: Among the 309 patients followed for the duration of the study, 137 (44.3%) interrupted their antiprotease treatment at least once. Withdrawal was warranted by therapeutic failure in 49.6% of the cases and by dug into lerance in 45.4%. Drug intolerance concerned 37%, 36.7%, 5.7% and 2.9% of t he patients taking ritonavir, indinavir, nelfinavir and saquinavir respecti vely (p < 106). Multivariate analysis demonstrated that saquinavir was sign ificantly associated with better tolerance and with efficacy at least as go od as ritonavir or indinavir. The most frequent cause for interrupting trea tment were digestive disorders for ritonavir (20% of the treated patients) and lithiasic manifestations for indinavir (9.4%). The ritonavir-hepatitis C association appeared to predispose to drug-induced perturbed liver tests. CONCLUSION: Drug intolerance is a frequent cause of treatment interruption. Therapeutic success in HIV infection requires improved efficacy but also b etter tolerated antiretorviral drugs, particularly antiretroviral drugs.