Nelfinavir is one of several currently available
protease inhibitors used to limit viral replication and improve immune function in HIV-infected individuals. It is administered in combination with other
antiretroviral agents.
Nelfinavir has been evaluated as first-line
therapy with
nucleoside reverse transcriptase inhibitors (NRTIs) in treatment-naive patients, or as an additional
antiretroviral agent in
protease inhibitor-naive patients already receiving NRTIs. These studies have shown good efficacy in terms of HIV viral load reduction and increased CD4+ cell counts. When used in combination with NRTIs,
nelfinavir 1250 mg twice daily produced similar results to 750 mg 3 times daily. The more convenient twice-daily dosage schedule, which is now approved in the US, may be beneficial in improving patient adherence to
therapy.
Nelfinavir has also been used successfully in combination with non-
nucleoside reverse transcriptase inhibitors and/or other
protease inhibitors, with or without NRTIs. Resistance to
nelfinavir has been observed in vitro and in clinical isolates from patients experiencing insufficient or waning viral suppression during treatment.
Nelfinavir primarily selects for the D30N mutation, which is not seen with other
protease inhibitors, and alone does not cause resistance to other
protease inhibitors in vitro. Several studies have shown that patients who experience virological failure while receiving
nelfinavir can respond to
salvage therapy with other
protease inhibitors. Diarrhoea is the most frequent adverse event in patients receiving
nelfinavir-based combination
therapy, but was generally mild and resulted in minimal discontinuation of
therapy in clinical trials. Diarrhoea can usually be controlled with drugs that slow gastrointestinal motility. Metabolic disturbances associated with
protease inhibitor use (hypercholesterolaemia, hyperglycaemia and
lipodystrophy) have also been reported with
nelfinavir.
Nelfinavir is associated with a number of clinically significant drug interactions and coadministration of some drugs (e.g.
astemizole,
cisapride,
triazolam) is contraindicated. Coadministration of
nelfinavir with other
protease inhibitors generally resulted in favourable pharmacokinetic interactions (usually increased area under the concentration-time curve for both drugs).
CONCLUSION: