Fosamprenavir (
GW433908,
Lexiva,
Telzir) is an oral
prodrug of the
protease inhibitor (PI)
amprenavir, with a reduced daily pill burden.
Fosamprenavir, in combination with other
antiretroviral agents, is indicated for the treatment of patients with
HIV infection, particularly those who have not previously received antiretroviral
therapy. Viral load reductions were at least as great with
fosamprenavir-based regimens as those achieved with
nelfinavir-based regimens in two large, 48-week, randomised, multicentre trials in antiretroviral
therapy-naive patients with
HIV infection. In the NEAT study, more patients receiving twice-daily
fosamprenavir in combination with
abacavir and
lamivudine achieved HIV
RNA levels <400 copies/mL than those receiving a similar
nelfinavir-based regimen. Results of the SOLO study showed similar reductions in viral load among patients who received once-daily
ritonavir-boosted
fosamprenavir and those treated with twice-daily
nelfinavir, both in combination with twice-daily
abacavir and
lamivudine. In both trials, virological failure rates were at least twice as high with the
nelfinavir-based regimen as they were with the
fosamprenavir-based regimen.
Fosamprenavir was generally well tolerated in clinical trials. The most common adverse events among patients treated with
fosamprenavir, with or without
ritonavir, plus
abacavir and
lamivudine were diarrhoea,
nausea,
vomiting,
abdominal pain,
drug hypersensitivity and
skin rash. The incidence of diarrhoea was significantly lower with
fosamprenavir-based
therapy than with
nelfinavir-based
therapy in the NEAT and SOLO trials. The resistance profile of
fosamprenavir is consistent with that of
amprenavir.
Amprenavir-resistant viral isolates from patients experiencing treatment failure with
fosamprenavir-based
therapy in the NEAT study showed little or no cross-resistance to several other PIs, and
protease mutations commonly selected for by various other PIs were not observed. In the SOLO study,
protease resistance mutations were not observed in viral isolates from patients experiencing treatment failure with
ritonavir-boosted
fosamprenavir-based
therapy. In conclusion,
fosamprenavir-based regimens have shown good
antiviral efficacy and are generally well tolerated in antiretroviral
therapy-naive patients with
HIV infection. Available data on the resistance profile of the
drug suggest that it may be used early in the course of
therapy without compromising a range of future treatment options. The relatively low pill burden and lack of food restrictions with
fosamprenavir may improve adherence to
therapy. Further studies are needed to compare
fosamprenavir with other PIs and to establish the long-term efficacy of
fosamprenavir-based regimens. In conclusion,
fosamprenavir appears to be a promising agent for the treatment of antiretroviral
therapy-naive patients with
HIV infection.