Final results of CPCRA 046: a pilot study of antiretroviral management based on plasma genotypic antiretroviral resistance testing (GART0 in patients failing antiretroviral therapy
Originally Published on September 2, 1999
JD Baxter, DL Mayers, DN Wentworth, JD Neaton, TC Merigan, and the CPCRA 046 Study Team for the Terry Biern Community Program for Clinical Research on AIDS (CPCRA)
ABSTRACT: Objective: To determine the short-term effects of using genotypic antiretroviral resistance testing (GART) in the management of patients failing on a protease inhibitor and two nucleoside reverse transcriptase inhibitors.
Methods: Multicenter, randomized trial in patients with a viral load (VL) rebound after >/=16 weeks of triple drug therapy. Genotyping by ABI sequencing was perfo9rmed on all patients, followed by 1:1 randomization to either the GART arm of the No-GART arm. For the GART arm, genotype interpretation and suggested regimens were provided to clinicians. VL (bDNA) and CD4 counts were collected over 12 weeks.
Results: one hundred and fifty-three patients were randomized between July 1997 and December 1998, with a median baseline CD4 count of 230 cells/mm3 and a median plasma VL of 28,985 copies/mL. Eighty-two patients were failing indinavir, 51 nelfinavir, 11 ritonavir, and 9 saquinavir. Seventy-three percent of patient viruses had >/=1 major RT mutation and >/=1 major protease mutation. The primary endpoint was the change in VL from baseline to the average of the 4 and 8 week measurements: GART arm (-1.19 log10) versus No-GART arm (-0.6 log10) (P=).00001). The average difference between treatment groups at 12 weeks was 0.44 log10 (P=0.003). The effect of GART was consistent across all baseline subgroups: protease inhibitor failing regimen, CD4 counts, baseline VL, number of prior protease inhibitors and genotypic profile. The VL response within each arm correlated with the number of active drugs prescribed.
Conclusions: GART with expert interpretation in patients failing triple drug therapy was superior to No-GART as measured by short-term viral load responses. The impact of GART was similar for patients failing their first protease inhibitor and for those who had received multiple protease inhibitors.
