Nelfinavir: an update on its use in HIV infection

Drugs. 2000 Mar;59(3):581-620. doi: 10.2165/00003495-200059030-00014.


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: Nelfinavir, in combination with reverse transcriptase inhibitors and/or other protease inhibitors, is effective in limiting HIV replication and increasing CD4+ cell counts in HIV-infected adults and children. The convenience of its dosage administration, the low incidence of adverse events, and the potential for salvage therapies indicate that nelfinavir (as part of combined antiretroviral therapy regimens) should be considered as a first-line option in protease inhibitor-naive patients and in those unable to tolerate other protease inhibitors.

Publication types

  • Review

MeSH terms

  • Adult
  • Area Under Curve
  • Biological Availability
  • Child
  • Drug Interactions
  • Drug Therapy, Combination
  • HIV Infections / drug therapy*
  • HIV Protease Inhibitors / metabolism
  • HIV Protease Inhibitors / pharmacokinetics
  • HIV Protease Inhibitors / therapeutic use*
  • Half-Life
  • Humans
  • Metabolic Clearance Rate
  • Nelfinavir / metabolism
  • Nelfinavir / pharmacokinetics
  • Nelfinavir / therapeutic use*
  • Patient Compliance
  • Randomized Controlled Trials as Topic
  • Reverse Transcriptase Inhibitors / administration & dosage
  • Tissue Distribution
  • Virus Replication / drug effects


  • HIV Protease Inhibitors
  • Reverse Transcriptase Inhibitors
  • Nelfinavir