Amprenavir: a review of its clinical potential in patients with HIV infection

Abstract

The virological/immunological efficacy of amprenavir-containing combination regimens has been evaluated in a small number of clinical trials in patients with HIV infection. Amprenavir plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) was more effective than 2 NRTIs (in treatment-naive patients) or amprenavir monotherapy (in treatment-naive or -experienced patients) in double-blind trials. In the only direct comparison with another protease inhibitor as part of triple therapy, amprenavir was less effective than indinavir in treatment-experienced (protease inhibitor-naive) patients. Amprenavir was as effective as other protease inhibitors when given with abacavir in a small nonblind trial. Amprenavir is generally well tolerated (most events are mild or moderate). GI disturbance and rash are the principal treatment-limiting effects. Preclinical data suggest that amprenavir may have a low potential for metabolic disturbances (e.g. lipodystrophy, fat redistribution); such effects have been infrequent in patients treated to date, but longer term experience is needed. 150V is the major HIV protease substitution associated with amprenavir resistance; this mutation is not seen in isolates from patients receiving other available protease inhibitors. Amprenavir-resistant isolates evaluated to date showed no significant cross-resistance to most other protease inhibitors, although some cross-resistance to ritonavir was noted. Many isolates from patients previously treated with other protease inhibitors are susceptible to amprenavir. Amprenavir offers the convenience of twice-daily administration with no food-timing or fluid restrictions, but this may be offset by the large number and size of the capsules. However, pharmacokinetic data support the use of co-administration of amprenavir and ritonavir at reduced dosages, thereby allowing a reduction in the number of amprenavir capsules.

Conclusions: Amprenavir-containing combination regimens have shown virological efficacy, and have generally been well tolerated, in patients with HIV infection (primarily treatment-naive or protease inhibitor-naive). The limited number of studies available and the absence of well controlled comparisons with other triple therapies limits the conclusions that can be drawn at present. The clinical value of amprenavir for patients with isolates which are resistant to other protease inhibitors but sensitive to amprenavir, and in treatment-experienced patients in general, requires further investigation. Further evaluation of the amprenavir/ritonavir combination is awaited with interest. Like other members of its class, amprenavir has a particular profile of tolerability, resistance and administration characteristics which should be carefully considered in relation to the needs of individual patients.