14th International HIV Drug Resistance Workshop 7-11 June 2005, Québec City, Canada

DETERMINATION OF PHENOTYPIC CLINICAL CUTOFFS FOR ATAZANAVIR AND ATAZANAVIR/RITONAVIR FROM AI424-043 AND AI424-045

Antivir Ther. 10, Suppl 1:S8 (abstract no. 6)

EP Coakley¹, C Chappey¹, JF Maa², S Wang², M Bates², V Wirtz² and D Seekins^2
1ViroLogic, Inc, South San Francisco, CA, USA; ²Bristol-Myers Squibb Virology, Plainsboro, NJ, USA

BACKGROUND: Atazanavir (ATV) (400 mg daily) and ATV/r (ATV 300 mg daily with ritonavir 100 mg daily) are widely used in combination treatment of HIV-1. The PhenoSense assay currently utilizes a biologic cutoff for ATV at 2.3-fold change (FC). The current study seeks to define a phenotypic clinical cutoff for ATV and ATV/r, above which virological response to therapy begins to decrease.

METHODS: Data from two clinical trials in subjects with prior PI failure, BMS AI424-043 (ATV+2NRTIs) and AI424-045 (ATV/r+TDF+1NRTI), were included for all subjects having baseline phenotype, baseline viral load ≥400 copies/mL, and viral load at weeks 12 and/or 24 (ATV n=131 and ATV/r n=111). ATV phenotyping (PhenoSense) was performed at baseline and correlated with virological outcome within each study. Efficacy outcomes focused on change in viral load from baseline and the proportion of subjects with HIV RNA levels <400 copies/mL at week 24. Logistic regression and Fischer’s exact tests were used to identify the ATV and ATV/r FC cutoffs.

RESULTS: For the 043 and 045 studies, the median baseline HIV-1 RNA value was 15,477 and 29,898 copies/mL, respectively, and the median (range) baseline FC to ATV was 1.2 (0.4–90) and 1.2 (0.2–57), respectively. In 043, the proportion of subjects with HIV RNA <400 copies/mL at week 24 was relatively constant below 2.2-fold but was reduced at higher FCs (P=0.001). The proportions with HIV RNA <400 copies/mL for those with baseline ATV FC <2.2 and ≥2.2 were 76% and 45%, respectively. In 045, the proportion of subjects with HIV RNA <400 copies/mL at week 24 was relatively constant below 5.2-fold but was reduced at higher FCs (P<0.0001). The proportions with HIV RNA <400 copies/mL for those with baseline ATV FC <5.2 and ≥5.2 were 77% and 12%, respectively.

CONCLUSIONS: In these PI-experienced study populations the overall treatment responses to ATV and ATV/r were good. Optimum responses to ATV were observed at FCs <2.2 in the 043 cohort and to ATV/r at FCs <5.2 in the 045 cohort.

PRESENTING AUTHOR: EP Coakley

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2005-06-07
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