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Modulation of K65R selection by zidovudine inclusion: analysis of HIV resistance selection in subjects with virologic failure receiving once-daily abacavir/lamivudine/zidovudine and tenofovir DF (study COL40263)
- Source :
- AIDS research and human retroviruses. 25(7)
- Publication Year :
- 2009
-
Abstract
- COL40263 was a pilot 48-week, open-label, multicenter study evaluating the efficacy and safety of once-daily coformulated abacavir/lamivudine/zidovudine plus tenofovir in ART-naive, HIV-infected subjects. We examined the patterns of resistance that were selected on-therapy through 48 weeks in subjects with virologic nonresponse (VF). A total of 123 antiretroviral-naive HIV-1-infected subjects with plasma HIV-1 RNAor = 30,000copies/ml were enrolled. For subjects with confirmed VF (HIV-1 RNAor = 400 copies/ml at week 24 or later), HIV population genotypic and phenotypic analysis was performed. Of the 123 enrolled subjects, 14 (11%) had confirmed plasma HIV-1 RNAor = 400 copies/ml through week 48. Of these subjects, 3/14 had evidence of drug resistance at baseline: 2/14 had HIV with K103N, Y188F/H/L/Y, and/or T215A and 1/14 had reduced zidovudine susceptibility. At the last time point analyzed, 4/14 subjects had wild-type HIV, while 10/14 subjects had HIV with either thymidine analogue mutations (TAMS) alone (3/10), TAMS + M184V (4/10), M184V only (1/10), or K65R/K (2/10). Matched phenotype was obtained for 13/14 subjects and 8/13 (62%) subjects had reduced susceptibility to one or more study drugs: 2/13 tenofovir, 3/13 abacavir, 4/13 zidovudine, and 7/13 lamivudine. The resistance pattern in COL40263 subjects with VF differs significantly from that reported for tenofovir-containing triple-nucleoside regimens. TAMs were detected in the majority (7/10) of samples from subjects with VF who selected any resistance mutation. These data suggest that TAMs selection is a preferred resistance route of this combination, with zidovudine modulating the resistance pathway against selection for K65R.
- Subjects :
- Adult
Male
medicine.medical_specialty
Anti-HIV Agents
Immunology
Population
Organophosphonates
HIV Infections
Pilot Projects
Drug resistance
Drug Administration Schedule
Zidovudine
Pharmacotherapy
Drug Resistance, Multiple, Viral
Abacavir
Virology
Internal medicine
medicine
Humans
Treatment Failure
education
Tenofovir
education.field_of_study
biology
business.industry
Abacavir/Lamivudine/Zidovudine
Adenine
virus diseases
Lamivudine
Middle Aged
biology.organism_classification
Dideoxynucleosides
Infectious Diseases
Amino Acid Substitution
Lentivirus
HIV-1
RNA, Viral
Female
business
medicine.drug
Subjects
Details
- ISSN :
- 19318405
- Volume :
- 25
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- AIDS research and human retroviruses
- Accession number :
- edsair.doi.dedup.....080f3ab01c03d6fd2db757c62c6a1bb2