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Frequency of antiretroviral drug resistance mutations in HIV-1 strains from patients failing triple drug regimens. The Terry Beirn Community Programs for Clinical Research on AIDS.
- Source :
-
Antiviral therapy [Antivir Ther] 2000 Mar; Vol. 5 (1), pp. 57-63. - Publication Year :
- 2000
-
Abstract
- The frequency of protease and reverse transcriptase (RT) gene mutations was determined in HIV-1 strains from 153 patients entering the CPCRA 046 (GART) study who were failing triple-drug regimens consisting of one protease inhibitor (PI) and two RT inhibitors. Population-based sequence analyses showed that nearly all patients had similar RT gene mutations regardless of prior drug exposure, although the M184V mutation was significantly less prevalent in patients not recently treated with lamivudine. Whilst typical inhibitor-specific ('signature') protease gene mutations were found in patients failing their first PI, these mutations were significantly less likely to be found in patients exposed to two or more PIs. Protease gene mutations associated with multi-PI resistance were more likely to be observed in patients treated with more than one PI. These results suggest sequential treatment with PIs select for a relatively limited number of protease gene mutations that likely originated during early PI therapy. These protease gene mutations and a similarly limited set of RT gene mutations appear to be responsible for treatment failure in antiretroviral therapy.
- Subjects :
- Anti-HIV Agents therapeutic use
Drug Resistance, Microbial genetics
Drug Therapy, Combination
HIV Infections drug therapy
HIV Infections virology
HIV Protease genetics
HIV Reverse Transcriptase genetics
HIV-1 enzymology
Humans
Reverse Transcriptase Inhibitors therapeutic use
Treatment Failure
Anti-HIV Agents pharmacology
HIV-1 drug effects
HIV-1 genetics
Mutation
Reverse Transcriptase Inhibitors pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1359-6535
- Volume :
- 5
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Antiviral therapy
- Publication Type :
- Academic Journal
- Accession number :
- 10846594