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.
CONCLUSION: 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.