Objective: To evaluate the efficacy and toxicity of salvage regimens containing ritonavir and saquinavir in patients failing highly active antiretroviral 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 with virological failure under HAART were treated with ritonavir (400mg twice daily) and saquinavir (600mg twice daily) and at least one reverse transcriptase inhibitor. HIV-RNA, CD4 cell counts and plasma concentrations of protease inhibitors were determined, and patients were monitored for toxicity at monthly intervals.
Results: Six patients showed complete virological success (HIV-RNA <200 copies/ml at week 12) which was sustained for a median follow-up of 6.3 months. Partial virological response (decrease of HIV-RNA of >1log10 at week 12) was achieved by a further three patients. Patients with a virological response had significantly higher CD4 cell increases than patients without virological response (mean increase at week 12: 66× cells/l versus 6 ×cells/l; P=0.01). No clinical events were observed during 6 months of follow-up. Neither the use of a non-nucleoside reverse transcriptase inhibitor (NNRTI) nor the number of newly introduced drugs influenced the virological response. Plasma concentrations of protease inhibitors did not statistically differ between patients with and without success. Toxicity included gastrointestinal disturbances, lipid abnormalities and liver dysfunction.
Conclusions: In extensively pretreated patients, salvage regimens containing ritonavir and saquinavir had only limited and short-term anti-HIV activity and were associated with substantial toxicity. Plasma concentrations of saquinavir were not predictive for virological response.
From the Department of Internal Medicine, University of Köln, Germany, the aDepartment of Pharmacy and Pharmacology, Slotervaart Hospital, Amsterdam, The Netherlands and the bDepartment of Internal Medicine, University of Bonn, Germany.
Sponsorship: The determination of plasma concentrations of protease inhibitors has been made possible by a grant of Abbott Germany, Wiesbaden, Germany.
Note: This paper was presented in part at the 12th World AIDS Conference, Geneva, June 28-July 3, 1998 [Abstract 12316].
Correspondence to Dr Gerd Fätkenheuer, Klinik I für Innere Medizin, Universität zu Köln, D-50924 Cologne, Germany.
Received: 4 January 1999; revised: 17 May 1999; accepted: 27 May 1999.