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.