A randomized study of antiretroviral management based on plasma genotypic antiretroviral resistance testing in patients failing therapy

Objective: To determine the short-term effects of using genotypic antiretroviral resistance testing (GART) with expert advice in the management of patients failing on a protease inhibitor and two nucleoside reverse transcriptase inhibitors. Design: Prospective randomized controlled trial. Setting: Multicenter community-based clinical trials network. Patients: One-hundred and fifty-three HIV-infected adults with a threefold or greater rise in plasma HIV-1 RNA on at least 16 weeks of combination antiretroviral therapy. Interventions: Randomization was either to a GART group, where genotype interpretation and suggested regimens were provided to clinicians, or to a no-CART group, where treatment choices were made without such input. Main outcomes measures: Plasma HIV-1 RNA levels and CD4 cell counts were measured at 4, 8, and 12 weeks following randomization. The primary endpoint was change in HIV-1 RNA levels from baseline to the average of the 4 and 8 week levels. Results: The average baseline CD4 cell count was 230 X 10(6) cells/l and the median HIV-1 RNA was 28 085 copies/ml. At entry, 82 patients were failing on regimens containing indinavir, 51 on nelfinavir, 11 on ritonavir, and nine on saquinavir. HIV-1 RNA, averaged at 4 and 8 weeks, decreased by 1.79 log(10) for the 78 CART patients and -0.61 log(10) for the 78 no-CART patients (treatment difference. -0.53 log, 95% confidence interval, -0.77 to -0.29; P=0.00001). Overall, the best virologic responses occurred in patients who received three or more drugs to which their HIV-1 appeared to be susceptible. Conclusion: In patients failing triple drug therapy, CART with expert advice was superior to no-CART as measured by short-term viral load responses. (C) 2000 Lippincott Williams & Wilkins.