Drug resistance mutations during structured treatment interruptions

Autor: Bernard Hirschel, Huldrych F. Günthard, Luc Perrin, Sabine Yerly, Catherine Fagard
Rok vydání: 2003
Předmět:
medicine.medical_specialty
HIV Infections/ drug therapy/virology
Anti-HIV Agents
Drug Resistance
Viral/ genetics
medicine.medical_treatment
HIV Infections
Drug resistance
Microbial Sensitivity Tests
Drug Administration Schedule
HIV Protease
Internal medicine
Antiretroviral Therapy
Highly Active
Drug Resistance
Viral
medicine
Humans
Pharmacology (medical)
RNA
Viral/blood
HIV-1/ drug effects/genetics/physiology
ddc:616
Pharmacology
Chemotherapy
Reverse Transcriptase Inhibitors/ administration &
business.industry
HIV Protease/genetics
Lamivudine
Drug holiday
Resistance mutation
HIV Reverse Transcriptase
Anti-HIV Agents/ administration & dosage/pharmacology/therapeutic use
Surgery
Lamivudine/administration & dosage/pharmacology/therapeutic use
Infectious Diseases
Mutation
Dosage/pharmacology/therapeutic use
HIV-1
RNA
Viral
Reverse Transcriptase Inhibitors
Viral disease
Off Treatment
business
HIV Reverse Transcriptase/genetics
Viral load
medicine.drug
Zdroj: Web of Science
Antiviral Therapy, Vol. 8, No 5 (2003) pp. 411-415
ISSN: 1359-6535
Popis: 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 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 b'ut 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.
Databáze: OpenAIRE
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