Efficacy of salvage therapy containing ritonavir and saquinavir after failure of single protease inhibitor-containing regimens

Objective: To assess the efficacy of salvage therapy containing ritonavir and saquinavir after failure of indinavir- or nelfinavir-containing regimens, and to determine correlates of success or failure. Design: Retrospective chart review. Setting. The Moore Clinic - the HIV clinic of Johns Hopkins Hospital. Patients: Forty-one HIV-infected patients were identified through physician contacts, referrals from other providers, and review of a comprehensive clinical database. Main outcome measures: To determine response to salvage therapy, HIV-1 viral RNA (absolute and log(10)-transformed) was measured using the Roche Amplicor quantitative HIV-1 RNA assay after initiation of the salvage regimen. Potential correlates of response included: vital RNA at the time of switch; viral RNA at the time of switch as a percentage of baseline viral RNA; magnitude of decline in viral RNA; and the interval between virologic failure of single protease inhibitor therapy and switch to the salvage regimen. Results: Thirteen (56.5%) of 23 patients failing indinavir responded to salvage therapy (HIV RNA < 400 copies/ml) with persistence throughout the follow-up period (median of 37 weeks; range 18-67 weeks). Mean absolute viral RNA at the time of switch was 20 238 copies/ml (median, 9281) compared with 42 953 copies/ml (median, 24 650) for the 10 non-responders. Mean log(10) viral RNA at switch was 3.804 for responders versus 4.405 for non-responders (P = 0.040). Among four responders who had failed nelfinavir, mean viral RNA was 9634 copies/ml and mean log(10) viral RNA was 3.749 at the time of switch. Two non-responders had a mean viral RNA of 21 551 and a mean log(10) viral RNA of 4.037 at switch. Conclusions: In contrast with previous reports, salvage regimens containing ritonavir and/or saquinavir can be effective and durable following the failure of combination regimens containing either indinavir or nelfinavir. Salvage therapy may be more likely to succeed when it is initiated early in failure at low viral loads. (C) 1999 Lippincott Williams & Wilkins.