A pilot study of the short-term effects of antiretroviral management based on plasma genotypic antiretroviral resistance testing (GART) in patients failing antiretroviral therapy.
authors
Baxter JD, Mayers DL, Wentworth DN, Neaton JD, Merigan TC and the and the CPCRA 046 Study Team.
publication
6th Conference on Retroviruses and Opportunistic Infections. 31 Jan-4 Feb, 1999, Chicago, IL. Abstract LB8.
ABSTRACT
Objective: To determine the short-term effects of using GART in patients (pts) failing on a protease inhibitor and two nucleoside reverse transcriptase inhibitors.
Methods: Multicenter, randomized trial in pts with a viral load (VL) rebound after > 16 wks of triple drug therapy. Genotyping by ABI sequencing was performed on all pts, followed by 1:1 randomization to either the GART arm or 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 wks.
Results: 153 pts were randomized between 7/97 - 12/98, with a mean baseline CD4 count of 230 cells/mm3 and a median plasma VL of 2,085 copies/ml. 82 pts were failing indinavir, 51 nelfinavir, 11 ritonavir, and 9 saquinavir. The primary endpoint, currently available for 94% of pts, was the change in VL from baseline to the average of the 4 and 8 wk measurements: GART arm (-1.14 log) vs. No-GART arm (-0.65 log) (p<0.001). The % pts with undetectable VL (<500 copies/ml) at 8 weeks: GART arm 50% vs. No-GART arm 23% (p=0.002). The average difference between treatment groups at 12 weeks was -0.39 log (p=0.02). The effect of GART was consistent across all baseline subgroups: failing regimen, CD4 counts, pt demographics, and genotypic profile. The virologic response within each treatment group 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.
