Primary nelfinavir (NFV)-associated resistance mutations during a follow-up period of 108 weeks in protease inhibitor naïve patients treated with NFV-containing regimens in an HIV clinic cohort

J Clin Virol. 2003 Aug;27(3):252-62. doi: 10.1016/s1386-6532(02)00179-8.

Abstract

Background: Nelfinavir (NFV) is a widely prescribed HIV-1 specific protease inhibitor (PI). However, there are only a few reports that have described the long-term effects of NFV-containing regimens, especially with regard to the emergence of drug resistance in inner-city clinics.

Objectives: The aim of this study was to investigate the clinical and virologic responses to treatment with NFV-containing regimens for up to 108 weeks and determine the timing and rate of emergence of primary NFV-resistance associated mutations in daily clinical practice.

Study design: A cohort study in an inner-city clinic. Our study included 51 consecutive patients who were PI-nai;ve and commenced therapy in February 1997 through April 1999.

Results and conclusions: The proportions of patients who continued the same therapeutic regimen and showed virologic success (viral load <400 copies/ml) up to 108 weeks were 78 and 63%, respectively, based on intent-to-treat analysis. Among patients with a viral load persistently >400 copies/ml at week 12 (n=30), 11 developed primary NFV-resistance associated mutations by 108 weeks (stratified log-rank test; P<0.05). The Cox proportional hazard model showed that prior use of reverse transcriptase inhibitors (n=22) (relative hazard (RH); 2.10, 95% CI; 0.67-6.62), prior AIDS diagnosis (n=6) (RH; 1.70, 95% CI; 0.37-7.77), CD4 < 200/microl at baseline (n=19) (RH; 2.48, 95% CI; 0.78-7.81) and viral load >30,000 copies/ml at baseline (n=21) (RH; 2.10, 95% CI; 0.67-6.62) were not independent predictors of the NFV-resistance, although some tendency was noted. In total, 77% of the patients continued NFV-containing treatment without the NFV-resistance for 108 weeks. The viral load at week 12 could be used as a predictor of treatment success in our cohort study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Ambulatory Care
  • Anti-HIV Agents / therapeutic use
  • Cohort Studies
  • Drug Resistance, Viral / genetics*
  • Drug Therapy, Combination
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Protease Inhibitors / pharmacology
  • HIV Protease Inhibitors / therapeutic use*
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation*
  • Nelfinavir / pharmacology
  • Nelfinavir / therapeutic use*
  • Retrospective Studies
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Sequence Analysis, DNA
  • Time Factors
  • Urban Population

Substances

  • Anti-HIV Agents
  • HIV Protease Inhibitors
  • Reverse Transcriptase Inhibitors
  • Nelfinavir

Associated data

  • GENBANK/AB020911
  • GENBANK/AB020912
  • GENBANK/AB020913
  • GENBANK/AB020914
  • GENBANK/AB020915
  • GENBANK/AB020916
  • GENBANK/AB020917
  • GENBANK/AB020918
  • GENBANK/AB020919
  • GENBANK/AB020920
  • GENBANK/AB020921
  • GENBANK/AB020922
  • GENBANK/AB020923
  • GENBANK/AB020924
  • GENBANK/AB020925