Salvage therapy with regimens containing ritonavir and saquinavir in extensively pretreated HIV-infected patients

Objective: To evaluate the efficacy and toxicity of salvage regimens contai ning ritonavir and saquinavir in patients failing highly active antiretrovi ral therapy (HAART), and to correlate outcome with plasma concentrations of protease inhibitors. Design: Prospective, non-randomized interventional study. Subjects and methods: Thirty extensively pretreated HIV-infected patients w ith virological failure under HAART were treated with ritonavir (400 mg twi ce daily) and saquinavir (600 mg twice daily) and at least one reverse tran scriptase inhibitor. HIV-RNA, CD4 cell counts and plasma concentrations of protease inhibitors were determined, and patients were monitored for toxici ty at monthly intervals. Results: Six patients showed complete virological success (HIV-RNA <200 cop ies/ml at week 12) which was sustained for a median follow-up of 6.3 months . Partial virological response (decrease of HIV-RNA of > 1 log(10) at week 12) was achieved by a further three patients. Patients with a virological r esponse had significantly higher CD4 cell increases than patients without v irological response (mean increase at week 12: 66 x 10(6) cells/l versus 6 x 10(6) cells/l; P = 0.01). No clinical events were observed during 6 month s of follow-up. Neither the use of a non-nucleoside reverse transcriptase i nhibitor (NNRTI) nor the number of newly introduced drugs influenced the vi rological response. Plasma concentrations of protease inhibitors did not st atistically differ between patients with and without success. Toxicity incl uded gastrointestinal disturbances, lipid abnormalities and liver dysfuncti on. Conclusions: in extensively pretreated patients, salvage regimens containin g ritonavir and saquinavir had only limited and short-term anti-HIV activit y and were associated with substantial toxicity. Plasma concentrations of s aquinavir were not predictive for virological response. (C) 1999 Lippincott Williams & Wilkins.