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Drug resistance mutations during structured treatment interruptions

Fagard, Catherine
Gunthard, Huldrych
Published in Antiviral therapy. 2003, vol. 8, no. 5, p. 411-415
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 useAntiretroviral Therapy, Highly ActiveDrug Administration ScheduleDrug Resistance, Viral/ geneticsHIV Infections/ drug therapy/virologyHIV Protease/geneticsHIV Reverse Transcriptase/geneticsHIV-1/ drug effects/genetics/physiologyHumansLamivudine/administration & dosage/pharmacology/therapeutic useMicrobial Sensitivity TestsMutationRNA, Viral/bloodReverse Transcriptase Inhibitors/ administration &Dosage/pharmacology/therapeutic use
PMID: 14640388
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YERLY FERRILLO, Sabine et al. Drug resistance mutations during structured treatment interruptions. In: Antiviral therapy, 2003, vol. 8, n° 5, p. 411-415. https://archive-ouverte.unige.ch/unige:7697

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Deposited on : 2010-06-21

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