448   Time to Appearance of NRTI-Associated Mutations and Response to Subsequent Therapy for Patients on Failing ABC/COM.

T. Melby*¹, S. Tortell¹, D. Thorborn², G. Pearce², W. Spreen¹, J. Scott¹, S. Madison¹, S. Lafon¹, and E. R. Lanier¹.
¹Glaxo Wellcome, Res. Triangle Park, NC and²Greenford, UK.

Background:The objective of this study was to examine viral resistance emerging following long-term initial therapy with ABC/COM and its impact on subsequent therapy success.

Methods:CNA3005 is a randomized, blinded study comparing ABC/COM and indinavir/COM in treatment- naïve adults. Amplicor Monitor and TrueGene assays were used to assess plasma viral copy number and genotype.

Results:To date, 43/262 (16%) of enrolled subjects on the ABC/COM arm of CNA3005 have had two consecutive viral RNA (vRNA) measurements >400 c/mL. Baseline and on-therapy genotypes are available for 40/43, and 34/40 developed one or more mutations associated with NRTIs. Thirty-two of these had a dominant virus with only the M184V mutation at the first genotype following failure, and 2 patients had virus with the M184V and 1—2 ZDV-associated mutations at this time point. Of those patients remaining on ABC/COM, fifteen patients who had a dominant M184V-only virus at a median of week 36 maintained this genotype at a median last follow-up of week 80 (median vRNA 3.5 log₁₀). Eleven additional patients who had a dominant M184V-only virus at the time of viral rebound (median 24 weeks) maintained this genotype until week 48 (median) and had second mutations develop (Y115F and/or ZDV-associated mutations) at a median of week 56 (median vRNA 2.9 log₁₀). The remaining patients either had a WT virus at all time points (n = 6), NRT- associated mutations at baseline (n = 4), or a single post-failure genotype (n = 4). Preliminary data on 10 subjects who switched from ABC/COM to open-label therapy with other ARTs after virologic failure and for whom data are available showed that 6/10 had plasma HIV-1 RNA >50 copies/mL and 8/10 had plasma HIV-1 RNA >400 copies/mL at the last time point assayed (24—68 weeks post switch).

Conclusions:Plasma viral rebound while receiving treatment with ABC/COM generally selects for a dominant M184V virus. Acquisition of subsequent mutations by plasma virus in patients remaining on ABC/COM is slow and does not result in large increases in vRNA over >6 months. Preliminary data from patients following viral rebound on ABC/COM indicate that a switch to subsequent treatments results in successful viral suppression.