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)

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 RNA ≥30,000copies/ml were enrolled. For subjects with confirmed VF (HIV-1 RNA ≥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 RNA ≥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...