Antiretroviral effect of two different dose regimens of ritonavir and saquinavir on HIV-infected adults in a population-based setting

Objective: To characterize the antiviral effect and tolerability of higher dose (HD, 600 mg two times daily) and lower dose (LD, 400 mg two times dail y) combination regimens of ritonavir and saquinavir in British Columbia (BC ), Canada. Design: Intent-to-treat analysis with suppression of plasma viral load to l evels below 500 copies/ml as the main outcome measure. Patients: Adult human immunodeficiency virus (HIV)positive individuals in t he province of British Columbia prescribed ritonavir and saquinavir in comb ination between 1 September 1996 and 30 June 1997, with a minimum of two pl asma viral loads, one at baseline and one after the initiation of therapy. Results: A total of 84 participants [27 HD (32%) and 57 LD (68%)] were pres cribed ritonavir and saquinavir. There was no difference at baseline in the two groups with respect to age (P=0.466), CD4 cell count (P=0.373) and bas eline plasma viral load (P=0.656). However, LD were more likely to have had prior protease experience than HD participants (65 versus 40%, P=0.037). T he median follow-up time was 9 months. A total of 44 (52%) subjects demonst rated a decrease in plasma viral load to levels <500 copies/ml. After adjus ting for length of follow-up, baseline CD4 cell count and prior AIDS diagno sis, HD participants were as likely to be suppressed to <500 copies/ml as L D individuals (P=0.760). HD participants did report more adverse effects (P =0.042) than LD subjects. Conclusion: Our results provide confirmatory evidence that lower doses of r itonavir and saquinavir in combination ave better tolerated and as effectiv e as the standard doses of these drugs. This response, however, is seriousl y compromised by prior exposure to protease inhibitors.