In:
Antiviral Therapy, SAGE Publications, Vol. 9, No. 1 ( 2004-01), p. 37-45
Abstract:
To evaluate HIV-1 reverse transcriptase genotypic and phenotypic indicators of resistance to abacavir (ABC) as predictors of ABC antiviral efficacy. Design The study was a retrospective, combined analysis of five multicentre trials in which ABC was added as a single agent to background antiretroviral therapy in experienced adults. Methods Baseline HIV-1 genotype and phenotypic susceptibility to ABC were determined and the association of genotype and phenotype with virological response after addition of ABC was analysed. Results Overall, 68% of these therapy-experienced subjects had a virological response ( 〉 0.5 log 10 or 〈 400 copies/ml; 42% 〈 400 copies/ml) 4 weeks after addition of ABC. Multivariable analyses revealed no significant difference in the response rate between subjects with wild-type virus and those carrying virus with 1–2 nucleoside reverse transcriptase inhibitor (NRTI)-associated mutations. At the 4-week time-point subjects harbouring virus with ≥3 mutations associated with NRTI resistance were significantly less likely to respond to ABC than were subjects harbouring wild-type virus ( P=0.015). However, at the last viral RNA measurement after addition of ABC (12-28 weeks), ≥4 mutations were required to diminish virological response significantly ( P=0.012). Phenotypic resistance was also predictive of antiviral response. Significant breakpoints were identified for virological responses for the PhenoSense™ HIV assay and the Antivirogram™ assay. CD4 responses generally paralleled the antiviral responses with a median increase of 55 cells/μl by weeks 12-28. Conclusions Virological response to ABC may be diminished significantly by multiple NRTI-associated mutations and/or by reductions in phenotypic susceptibility to ABC. However, many subjects with baseline samples showing evidence of resistance to NRTIs respond to ABC.
Type of Medium:
Online Resource
ISSN:
1359-6535
,
2040-2058
DOI:
10.1177/135965350400900102
Language:
English
Publisher:
SAGE Publications
Publication Date:
2004
detail.hit.zdb_id:
2118396-X
SSG:
15,3
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