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Session 75 Poster Session Resistance to Antiretroviral Chemotherapeutic Agents Session Time: 4:30-6:30 pm Room 4E-F

558-T. Correlation of Phenotypic Resistance and Virologic Response to Indinavir/Ritonavir Boosted Regimens H. Rice*1, A. Zolopa1, M. Coram1, U. Murlidharan1, N. Shulman1, C. Vaamonde2, J. H. Condra3, N. S. Hellmann4, H. King4, and M. Bates4 1Stanford Univ., Palo Alto, CA; 2Cornell Univ., New York, NY; 3Merck Res. Labs., West Point, PA; and 4ViroLogic, Inc., South San Francisco, CA Background: Ritonavir (RTV) boosting of indinavir (IDV) results in an enhanced pharmacokinetic profile, improved dosing convenience, and increased potency. We evaluated the degree of phenotypic resistance to IDV that could be overcome with RTV boosting in a clinical cohort. Methods: All patients from a university clinic who received IDV/RTV combination therapy were identified through a systematic review of medical records. Virologic response over time was measured using DAVG (24 weeks), defined as the time weighted average of HIV-1 RNA between the first post-baseline value through the last available value up to week 24, minus the baseline value. A significant response in DAVG (24weeks) was defined as a viral load decrease of greater than 0.5 log10 copies/mL. Phenotyping was performed on stored specimens ( ViroLogic). Results: We have identified 56 patients who had archived plasma specimens available before starting an IDV/RTV-containing regimen. Median duration of prior antiretroviral therapy was 62 months, median baseline CD4 count was 194, and the median baseline HIV-1 viral load was 4.8 log10 copies/mL. 71% had received 2 or more prior Pis. IDV/RTV doses were twice daily 400 mg/400 mg (24/56), 800 mg/200 mg (12/56), 800 mg/400 mg (5/56), 400 mg/200 mg (4/56), or other (11/56). The median IC50-fold change for IDV was 2.75 and ranged from 0.5 to >178. Significant virologic response by IDV fold change categories of <2.5, 2.5-25, and >25 was 71% (20/28), 63% (10/16), and 17% (2/12), respectively. However, only those patients who received a new NNRTI achieved a DAVG (24) of > 1 log decline if their baseline IDV FC was greater than 2.5. Univariate analysis using DAVG (24) revealed the following significant predictors: number of phenotypically sensitive drugs in the regimen (p=0.001), log IDV fold change (p=0.002), new NNRTI with the IDV/RTV regimen (p=0.002), and IDV dose of > 400 mg BID (p=0.03). Conclusions: In this heavily treatment-experienced clinical cohort, IDV/RTV-containing regimens demonstrated virologic activity in a majority of patients with IDV phenotypes of up to 25-fold change. Best responses were seen in patients whose baseline IDV FC was < 2.5 or who received a new NNRTI. The phenotypic cutoff defining complete response from partial response for IDV/RTV boosted regimens appeared to be an IDV FC of 2.5, while there was no clear cutoff defining partial response from no response.

©2002 9th Conference on Retroviruses and Opportunistic Infections