en
Scientific article
English

Drug resistance mutations during structured treatment interruptions

Published inAntiviral therapy, vol. 8, no. 5, p. 411-415
Publication date2003
Abstract

BACKGROUND: We assessed whether treatment interruptions induce selection of mutations associated with drug resistance in the Swiss-Spanish Intermittent Treatment Trial (SSITT). Patients had been on HAART without previous failure and had undetectable viraemia for at least 6 months. Their HAART was interrupted for 2 weeks and restarted for 8 weeks. After four of these cycles, treatment was definitively interrupted at week 40. METHODS: Genotypic resistance testing was performed in 87/97 Swiss patients: in those failing treatment before week 40, at the time of first viral rebound > 500 copies/ml off treatment and preceding failure to reach RNA < 50 copies/ml after 8 weeks of re-treatment; for patients without virological failure, on the first sample with HIV-1 RNA > 1000 copies/ml after week 40. RESULTS: Mutations associated with drug resistance were detected in 9/25 (36%) patients with virological failure during the first 40 weeks and in 6/59 (10%) patients after week 40. Overall, drug resistance mutations were detected in 17% of patients, all but two with the 184V/I mutation. Among the 74 patients receiving lamivudine, the M184V/I mutation was detected in 13/74 (17.6%) patients. A wild-type codon at position 184 was detected in previous samples in all but two. The relative risk for virological failure was 2.55-fold higher in patients with the M184V/I mutation than in patients without detectable mutation (P=0.007). CONCLUSIONS: The M184V/I mutation is frequently selected during repeated treatment interruptions.

Keywords
  • Anti-HIV Agents/ administration & dosage/pharmacology/therapeutic use
  • Antiretroviral Therapy, Highly Active
  • Drug Administration Schedule
  • Drug Resistance, Viral/ genetics
  • HIV Infections/ drug therapy/virology
  • HIV Protease/genetics
  • HIV Reverse Transcriptase/genetics
  • HIV-1/ drug effects/genetics/physiology
  • Humans
  • Lamivudine/administration & dosage/pharmacology/therapeutic use
  • Microbial Sensitivity Tests
  • Mutation
  • RNA, Viral/blood
  • Reverse Transcriptase Inhibitors/ administration &
  • Dosage/pharmacology/therapeutic use
Citation (ISO format)
YERLY FERRILLO, Sabine et al. Drug resistance mutations during structured treatment interruptions. In: Antiviral therapy, 2003, vol. 8, n° 5, p. 411–415.
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ISSN of the journal1359-6535
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