Saquinavir: a review of its use in boosted regimens for treating HIV infection

Protease inhibitor boosting involves concurrent administration of a protease inhibitor, such as saquinavir, plus a potent inhibitor of cytochrome P450 (CYP) 3A4, usually ritonavir in subtherapeutic doses. Since protease inhibitors are extensively metabolised by CYP3A4, this results in a marked increase in systemic exposure of saquinavir or other protease inhibitors boosted by ritonavir. As with traditional protease inhibitor regimens, boosted regimens are typically used in combination with nucleoside reverse transcriptase inhibitors (NRTIs). In protease inhibitor-experienced and -naive patients with HIV infection, twice-daily and once-daily boosted saquinavir regimens achieved good rates of viral suppression, improved CD4+ cell counts and were generally well tolerated in clinical trials. Encouraging results have also been reported in a number of small studies in heavily pretreated HIV-infected patients who received salvage therapy comprising double-boosted regimens of saquinavir plus lopinavir with subtherapeutic doses of ritonavir, along with other agents. The largest clinical trials have been multicentre, randomised comparisons of twice-daily boosted saquinavir versus twice-daily boosted indinavir (MaxCmin1) or lopinavir (MaxCmin2) regimens. In the MaxCmin1 study, >90% of patients in both groups had an undetectable viral load (<400 copies/mL) after 48 weeks of therapy in the on-treatment analysis. However, viral suppression was achieved in significantly more saquinavir than indinavir recipients in the intention-to-treat analysis, which appeared to be due to the significantly greater percentage of patients in the indinavir group who switched from randomised therapy because of adverse events. Interim 24-week results of the MaxCmin2 trial indicate that 90% of patients in both groups combined had plasma HIV RNA levels <400 copies/mL; final results at 48 weeks will report data separately for the boosted regimens of saquinavir and lopinavir.

Boosted protease inhibitor regimens (including two NRTIs) are recommended as a first-line option in current HIV treatment guidelines and are used extensively in clinical practice. The convenient administration schedule and good pharmacokinetic profile associated with boosted saquinavir regimens have the potential to increase adherence to therapy and improve antiretroviral effects through increased drug exposure. Twice-daily boosted saquinavir is one of the most extensively evaluated boosted protease inhibitor regimens and has been shown to have good efficacy on surrogate markers of HIV disease as well as significant tolerability advantages over boosted indinavir. Once-daily boosted saquinavir regimens may be most suitable for HIV-infected patients with busy lifestyles and those who would benefit from directly observed therapy.