title: 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.
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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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.
authors.affiliation: AIDS Clinical Center, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, 162-8655 Tokyo, Japan.
authors.forename: Kiyoto
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Saori
authors.initials: S
authors.lastname: Matsuoka-Aizawa
authors.forename: Akira
authors.initials: A
authors.lastname: Yasuoka
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Kikuchi
authors.forename: Natsuo
authors.initials: N
authors.lastname: Tachikawa
authors.forename: Ikumi
authors.initials: I
authors.lastname: Genka
authors.forename: Katsuji
authors.initials: K
authors.lastname: Teruya
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kimura
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oka
mesh_terms: D000328:Adult; D000368:Aged; D000553:Ambulatory Care; D019380:Anti-HIV Agents / Q000627:therapeutic use; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D019888:Nelfinavir / Q000494:pharmacology / Q000627:therapeutic use*; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D017422:Sequence Analysis, DNA; D013997:Time Factors; D014505:Urban Population
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D019888:Nelfinavir