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The reverse transcriptase (RT) mutation V118I is associated with virologic failure on abacavir-based antiretroviral treatment (ART) in HIV-1 infection
- Source :
- Scandinavian Journal of Infectious Diseases. 36:40-45
- Publication Year :
- 2004
- Publisher :
- Informa UK Limited, 2004.
-
Abstract
- Antiviral efficacy and serum lipids were investigated following a switch from long-term successful protease inhibitor based antiretroviral treatment (PI-ART) to abacavir-based ART in 29 patients who have been followed for 28 months thereafter. Virologic failure occurred within 3 months in 21% (6/29) of the patients, and abacavir hypersensitivity in 1 individual. The remaining 22 patients continue to have HIV RNA < 50 copies/ml after 28 months with a CD4 increase from 605 +/- 265 x 10(6)/l to 798 +/- 366 x 10(6)/l (p < 0.001). All virologic failing patients had been on long-term unsuccessful nucleoside reverse transcriptase inhibitor (NRTI) therapy before PI-ART as compared to 32% (7/22) of the virologic non-failing patients (p < 0.01). The viral strains from the virologic failing patients harboured 3-6 reverse transcriptase (RT) mutations, including the V118I mutation in 5/6 cases prior to PI-ART or at viral rebound. Only the V118I RT mutation was statistically more common among virologic failing than non-failing NRTI pretreated patients (p < 0.05). Stepwise multiple regression analysis for viral failure resulted in a model with only the V118I RT mutation entering the model (p < 0.01). The LDL cholesterol and triglyceride values decreased and the HDL cholesterol increased after the switch to abacavir-based ART (p < 0.01, p < 0.05, p < 0.05, respectively). In conclusion, viral failure was associated with prior mono- or dual-NRTI treatment and the occurrence of the V1181 RT mutation, persisting despite long term viral control. The selection process for patients suitable for treatment simplification to abacavir-based ART should contain a detailed antiretroviral treatment history.
- Subjects :
- Adult
Male
Microbiology (medical)
HIV Infections
Virus Replication
Risk Assessment
Drug Administration Schedule
Statistics, Nonparametric
Nucleoside Reverse Transcriptase Inhibitor
Abacavir
medicine
Humans
Single-Blind Method
Protease inhibitor (pharmacology)
Prospective Studies
Treatment Failure
Probability
Dose-Response Relationship, Drug
General Immunology and Microbiology
Reverse-transcriptase inhibitor
biology
RNA-Directed DNA Polymerase
General Medicine
Middle Aged
Viral Load
biology.organism_classification
Virology
Dideoxynucleosides
Reverse transcriptase
Infectious Diseases
Pharmacogenetics
Mutation
Lentivirus
HIV-1
Regression Analysis
Reverse Transcriptase Inhibitors
Female
Viral disease
Viral load
Follow-Up Studies
medicine.drug
Subjects
Details
- ISSN :
- 00365548
- Volume :
- 36
- Database :
- OpenAIRE
- Journal :
- Scandinavian Journal of Infectious Diseases
- Accession number :
- edsair.doi.dedup.....106bf14c574ad00f01d44f22fe915427