The Body Covers: The 6th International Congress on Drug Therapy in HIV Infection
Efficacy and Safety of Once-Daily 908/Ritonavir in Therapy-Naive Subjects
November 21, 2002
The current study reports on one such PI, currently being developed by GlaxoSmithKline (GSK), that indeed appears able to maintain activity against multiple strains of HIV that contain mutations in protease (PR) associated with resistance to all currently approved PIs. Moreover, GW433908 appears to possess another major advantage. Notably, it can be boosted with ritonavir (RTV, Norvir) to attain high plasma levels that appear to maintain values above the Cmin for this agent over more than 24 hours. This means that the combination of GW433908/ritonavir (GW433908/r) might lend itself to once-daily dosing and mimic the dosing profiles of other novel PIs such as atazanavir (BMS-232623, Zrivada).
Accordingly, the current study was undertaken to assess the efficacy over 48 weeks of GW433908/ritonavir when combined with 3TC (lamivudine, Epivir) and abacavir (ABC, Ziagen), both of which were administered twice-daily (BID). Moreover, this GW433908/ritonavir combination was compared in a randomized controlled trial against nelfinavir (NFV, Viracept) BID plus the same two nucleosides. Patients in this multi-center trial (n=649) began with a plasma viral load of about 4.8 log copies RNA/ml (43 percent had viral loads more than 100,000 copies/ml) and a median CD4 count of 170 cells/mm3 (20 percent had less than 50 cells/mm3).
The results of both as treated and intent-to-treat analyses show that both of these regimens yielded similar results after 48 weeks, based on ability to cause reductions in plasma viral load to levels below cutoffs of either 400 or 50 viral RNA copies/ml.
In general, the incidence of adverse events was comparable between the two groups and the incidence of triglyceride and cholesterol-related abnormalities were low (6 percent vs. 2 percent and 1 percent vs. 0 percent for GW433908/ritonavir vs. nelfinavir, respectively), in spite of the fact that ritonavir was used at 200 mg once daily in the GW433908-containing regimen.
Hence, GW433908 appears to be a potent PI that maintains durability and tolerability in treatment-naive subjects who began therapy with high viral loads and low CD4 counts. The fact that GW433908/ritonavir can be dosed once daily makes this combination, together with its favorable resistance profile, an excellent candidate for further study. Caution, of course, must be applied in regard to the need for longer follow-up. Nonetheless, these 48-week data are very encouraging for patients and physicians.
This article was provided by The Body PRO. Copyright © Body Health Resources Corporation. All rights reserved.