Saquinavir is an
HIV protease inhibitor which, formulated as a hard-gel
capsule (HGC), was the first
drug of its class to become available for the treatment of patients with
HIV infection. Despite the beneficial effects that
saquinavir HGC-containing combination regimens have shown in the treatment of patients with
HIV infection, the HGC formulation has limited oral bioavailability and has shown only modest
antiviral activity in vivo. To overcome this limitation (with the aim of improving
antiviral efficacy), a soft-gel
capsule (SGC) formulation of the
drug has been developed. At the recommended dosage of 1200 mg 3 times daily, the SGC formulation of
saquinavir achieves plasma concentrations > 8 times higher than those in patients receiving
saquinavir HGC 600 mg 3 times daily. Initial results of trials evaluating the therapeutic efficacy of
saquinavir SGC-containing combination
therapy in patients with moderate to advanced
HIV infection are promising. In patients who were previously antiretroviral
therapy-naive or -experienced, short term (< or = 36 weeks) treatment with
saquinavir SGC in combination with > or = 2
nucleoside reverse transcriptase inhibitors (NRTIs), or
nelfinavir, or 2 NRTIs plus
nelfinavir led to marked improvements in virological and immunological markers of HIV disease. In comparative trials,
saquinavir SGC showed improved
antiviral activity compared with the HGC formulation in terms of reducing viral load. Furthermore,
saquinavir SGC in combination with 2 NRTIs was as effective as
indinavir plus 2 NRTIs in antiretroviral-naive or -experienced patients. Available data suggest that
saquinavir SGC-containing combination
therapy may be of greatest benefit in patients naive to previous antiretroviral
therapy. The SGC formulation of
saquinavir appears to be generally well tolerated by adults with
HIV infection. Gastrointestinal adverse events, notably diarrhoea, abdominal discomfort,
nausea and
dyspepsia, are the most common adverse events occurring during treatment with the
drug. Initial results of several trials that used
surrogate markers to assess treatment efficacy indicate that the SGC formulation of
saquinavir, administered in combination with other antiretroviral drugs, is an effective and well-tolerated treatment for patients with moderate or advanced
HIV infection. Although further data are required before definitive conclusions can be drawn regarding the comparative efficacy and tolerability of the SGC and HGC formulations, it appears likely that the SGC formulation will replace the conventional formulation as a component of combination regimens for the treatment of patients with
HIV infection.