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Session 121 Poster Abstracts
Impact of Drug Resistance on Virologic Response and Clinical Outcomes
Friday, 1:30 - 3:30 pm
Hall A


711
The Influence of Baseline Protease Inhibitor Mutations on the Efficacy of Ritonavir-Boosted Atazanavir, Atazanavir plus Saquinavir, and Lopinavir/Ritonavir in Patients Who Have Experienced Virologic Failure on Multiple HAART Regimens
Margaret Johnson*1, E DeJesus2, C Rodriguez3, L Nieto-Cisneros4, A Rightmire5, C McLaren6, and L Odeshoo6
1Royal Free Hosp, London, UK; 2IDC Res Initiative, Altamonte Springs, FL, USA; 3Hosp Argerich, Buenos Aires, Argentina; 4Hosp Gabriel Mancera, IMSS, Mexico City, Mexico; 5Bristol-Myers Squibb, Hopewell, NJ, USA; and 6Bristol-Myers Squibb, Wallingford, CT, USA

Background:  Patients who have failed multiple HAART regimens may have virologic protease inhibitor (PI)–resistance mutations that can limit their response to subsequent therapy. This study examined the effect of the number of baseline PI mutations on the long-term (96-week) virologic response in patients on 3 different regimens.

Methods:  A post hoc efficacy analysis of the influence of baseline PI mutations on virologic response was performed on patients participating in a randomized, open-label study (BMS AI424-045) comparing the efficacy and tolerability of atazanavir (ATV; 300 mg)/ritonavir (RTV; 100 mg once daily), n = 120; ATV (400 mg)/saquinavir (SQV; 1200 mg once daily), n = 115; and lopinavir (LPV; 400 mg)/RTV (100 mg twice daily), n = 123. All subjects also took 300 mg tenofovir + a nucleoside reverse transcriptase inhibitor. Patients had a range of 0 to 10 PI mutations at baseline (based on the Stanford set of 16 ATV- or LPV-related mutations), reflecting a mean of 138 weeks on prior PI therapy. Patients were analyzed by the number of baseline PI mutations (< 4 or ≥ 4). Changes in log10 HIV RNA from baseline through week 96 were summarized.

Results:  Overall for randomized subjects, the mean log10 HIV RNA changes from baseline through week 96 were similar for ATV/RTV (–2.29) and LPV/RTV (–2.08), time-averaged difference (TAD) 0.14 97.5% confidence interval (CI –0.13 to 0.41]. However, ATV/SQV was less effective than LPV/RTV (–1.96; TAD 0.35, 97.5% CI 0.07 to 0.63). In those who had ≥ 4 baseline PI mutations, the week 96 mean change in HIV RNA was –1.71 for ATV/RTV, –0.93 for ATV/SQV, and –1.81 for LPV/RTV. A consistent pattern was observed for those with < 4 PI mutations, but the decreases were larger (–2.47, –2.17, and –2.21, respectively). 

Conclusions:  The ATV/RTV-containing regimen demonstrated similar efficacy compared with LPV/RTV regardless of the number of baseline PI mutations. The ATV/SQV-containing regimen was less effective regardless of the number of baseline PI mutations. With all regimens, the magnitude of response was inversely related to the number of baseline PI mutations, with greater mean reduction in HIV RNA in patients with < 4 PI mutations compared with those with ≥ 4 PI mutations.

Keywords: atazanavir; resistance; mutations