3rd IAS Conference on HIV Pathogenesis and Treatment
July 24 - 27, 2005, Rio de Janerio, Brazil
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Treatment-naïve Patients Treated with Ritonavir-boosted Saquinavir Show No Significant Resistance to Protease Inhibitors Prior studies show that resistance develops less often with the use of first-line ritonavir-boosted PI therapy compared with the use of unboosted PI. Limited data exists on the development of resistance following treatment with ritonavir-boosted saquinavir (Invirase, SQV/r). 258 ART-naïve Thai patients with a baseline CD4 count 200–350 cells/mm3 received SQV/r 1600/100mg QD plus d4T/ddI for >/= 6 months. Viral load (VL) failure (VF) was defined as two consecutive viral loads >500 copies/ml after >/= 12 weeks of therapy. Analyses were by intent-to-treat. Results · 10/258 (3.9%) patients experienced VF after a median of 29.6 (range 19–48) weeks; their median VL at VF was 1410 copies/ml (range 784–765,000). · At VF 6/8 patients had SQV Cmin >50ng/ml. · NRTI-resistance mutations were detected in three (30%) VF patients. · No patient acquired primary PI-resistance mutations. · At VF, 7 patients had other protease substitutions (L10I, K20R, M36I, L63V/P), all of which are natural polymorphisms/secondary mutations and in 4 cases were documented at baseline. · At VF all patients had SQV/r increased to 1000/100mg BID. · Three patients then achieved VLs <50 copies/ml. 4/5 patients who switched to NNRTI-based HAART achieved VLs <50 copies/ml and ¼ achieved VL of 64 copies/ml. · One patient stopped treatment. · One patient was non-adherent and did not achieve undetectable VL. The authors concluded that there was a very low incidence of viral failure in ART-naïve patients receiving SQV/r (3.9%). No patient acquired major PI-resistance mutations. The protease polymorphisms detected at VF are similar to those seen with other boosted PIs in ARV-naïve patients, and are natural polymorphisms/secondary mutations that may contribute to reduced susceptibility in the presence of primary mutations. “The incidence of genotypic NRTI-resistance at VF was low. Most patients with viral failure achieved VL <50 copies/ml after increasing SQV/r dosing or switching to another regimen.” “These data show that early treatment with [ritonavir-boosted]-Invirase [saquinavir hard gel capsule] resulted in an outstanding level of HIV suppression without the development of significant protease inhibitor resistance,” said lead investigator Jintanat Ananworanich, M.D., of the HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Bangkok. In December 2004, Roche received approval from the US Food and Drug Administration (FDA) of a new 500 mg film-coated tablet formulation of saquinavir (Invirase), designed for use in combination with low dose of ritonavir (Norvir) and other anti-HIV drugs for the treatment of HIV infection. The new formulation of Invirase reduces pill count for each dose by more than half (from five pills to two, twice-daily) compared to the Invirase 200 mg capsules. The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Bangkok, Thailand; 2Chulalongkorn University, Bangkok, Thailand; 3Roche Welwyn, UK; 4NCHECR, University of New South Wales, Sydney, Australia; Geneva University Hospital, Geneva, Switzerland. 07/29/05 Reference |
