592 CREST-A Randomized Comparison of Genotype and Genotype Plus Virtual Phenotype (VircoGen II) S. Emery*1, G. Hales1, C. Birch2, S. Crowe4, J. Hoy5,6, C. Workman7, A. Kellerher1, A. Rinehart8, P. McKenna8, M. Law1 1Univ of New South Wales, Sydney, Australia; 2Victorian Infectious Disease Reference Lab, Melbourne, Australia; 3Burnet Inst, Melbourne, Australia; 4Alfred Hosp, Melbourne, Australia; 5Monash Univ, Melbourne, Australia; 6AIDS Res Initiative, Sydney, Australia; 7Tibotec-Virco USA, Durham, NC; and 8Tibotec-Virco BVBA, Mechelen, Belgium
Background: HIV drug-resistance testing at the time of antiretroviral therapy (ARV) change is associated with improved surrogate marker outcomes. A number of different platforms have been developed to provide interpretation of genotypic sequences from clinical HIV isolates. We performed a randomized study in which patients (pts) received either an HIV genotype or genotype + VircoGen II prior to selecting a new ARV regimen.
Methods: Pts currently taking ARV therapy with a plasma HIV RNA > 2,000 copies/ml were eligible and were randomly assigned to receive an HIV drug-resistance report derived from a uniform, rules based interpretation of a genotype (arm A) or genotype + VircoGen II (arm B). The following variables were collected at 1, 3, 6, 9 and 12 months after initiation of the new ARV regimen: plasma HIV RNA, CD4+ cell count, changes to ARV; therapy could be changed during the study if toxicity, intolerance, or treatment failure occurred. Arm A was compared with arm B for surrogate marker outcomes on an intention to treat basis.
Results: A total 338 pts entered the trial; 327 completed at least completed 1 month follow-up and were included in these analyses. Baseline factors were balanced across arms A and B: median CD4+ cell count 290 and 318 cells/mm3, median HIV RNA viral load 16750 and 16,300 copies/mL respectively. Resistance test results were the primary means by which the next regimen of ARV was selected (arm A: 64% and arm B: 62% p = 0.32). At baseline, viral isolates were defined as sensitive to a median of 6 drugs and 8 drugs (p < 0.001) in Arms A and B, respectively. In Arm A, pts were prescribed a mean of 1 sensitive drug compared with 2 sensitive drugs in Arm B (p < 0.0001). At 48 wks, there were no significant differences between the arms for mean change from baseline plasma HIV RNA (Arm A = -0.68 log copies/ml, Arm B = -0.58 log copies/ml: p = 0.23), or mean change from baseline CD4+ cell count (Arm A = 37 cells mm3, Arm B = 50 cells mm3; p = 0.28). Treatment arms at 48 wks were not significantly different in terms of the percentage of pts with undetectable (< 400 copies/ml) HIV RNA viral load (p = 0.5), the time to treatment failure (p = 0.4), or the time to treatment change (p = 0.9).
Conclusions: There were no significant differences in virological or immunological outcomes between pts randomized to receive a genotype or a genotype + VircoGen II after 48 wks of follow-up.