Resistance

As with all other anti-HIV drugs, strains of HIV that are resistant to nelfinavir (Viracept) may emerge after a period of treatment. The emergence of drug-resistant strains coincides with a fall in the effectiveness of the drug .

Nelfinavir resistance is primarily associated with one key mutation at position D30N on the gene for the protease enzyme. This seems to cause greater resistance in sub-type C than sub-type B virus.1 2 However, the following mutations are also associated with nelfinavir resistance:

  • M46I/L.
  • G48V.
  • I54V.
  • V82A/T/F/S.
  • I84V.
  • N88D/S/T.
  • L90M.3

When nelfinavir and saquinavir (Invirase) are taken together, the L90M mutation is most commonly associated with treatment failure.4

There is some evidence that nelfinavir-resistant strains of HIV do not reproduce efficiently and may not be as damaging to the immune system as other types of mutant virus. The implications of this are unclear, although it has been suggested that CD4 cell counts may continue to rise despite a rebound in HIV that is resistant to nelfinavir.

Following nelfinavir failure, there is a possibility that a patient will still benefit from indinavir (Crixivan), Kaletra or dual protease inhibitor therapy, but there is a reduced chance of benefiting from saquinavir (Invirase). One study found that people who took nelfinavir as their first-line protease inhibitor were much less likely to have cross-resistance to other protease inhibitors compared with people who took another protease inhibitor in their first anti-HIV combination.

There is some evidence that patients whose treatment based on indinavir or saquinavir has failed may benefit from nelfinavir, although the saquinavir-associated L90M mutation may cause cross-resistance to nelfinavir.5 6 7 8 9 Patients whose treatment based on full-dose ritonavir (Norvir) has failed are also unlikely to benefit from nelfinavir.

References

  1. Gonzalez LMF et al. Impact of nelfinavir resistance mutations on in vitro phenotype, fitness and replication capacity of human immunodeficiency virus type 1 with subtype B and C proteases. Antimicrobial Agents Chemother 48: 3552-3555, 2004
  2. Patick AK et al. Genotypic and phenotypic analyses of HIV-1 variants isolated from patients treated with nelfinavir and other HIV-1 protease inhibitors. International Workshop on Drug Resistance, Treatment Strategies and Eradication, Florida, abstract 18, 1997
  3. Svedhem V et al. Diverse pattern of protease inhibitor resistance mutationsnin HIV-1 infected patients failing nelfinavir. J Med Virol 76: 447-451, 2005
  4. Craig C et al. HIV-1 genotype and phenotype dual PI therapy (NV15436 sub-study). Seventh European Conference on Clinical Aspects and Treatment of HIV-Infection, Lisbon, abstract 103, 1999
  5. Nelson MR et al. Antiviral benefits of compassionate release nelfinavir. Fourth Annual Meeting of the British HIV Association, Oxford, abstract 21, 1998
  6. Hellinger JA et al. Efficacy of nelfinavir in patients switched from ritonavir / saquinavir combination antiretroviral therapy. HIV Clin Trials 1: 25-28, 2000
  7. Hammer S et al. Relationship of phenotypic and genotypic resistance profiles to virological outcome in a trial of abacavir, nelfinavir, efavirenz and adefovir dipivoxil in patients with virological failure receiving indinavir (ACTG 372). Antivir Ther 4: S45, 1999
  8. Lawrence J et al. Clinical resistance patterns and responses to two sequential protease inhibitor regimens in saquinavir and reverse transcriptase inhibitor-experienced persons. J Infect Dis 179: 1356-1364, 1999
  9. Casado JL et al. Plasma drug levels, genotypic resistance, and virological response to a nelfinavir plus saquinavir-containing regimen. AIDS 16: 47-52, 2002
Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap
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