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

564-T. Antiretroviral Resistance in ACTG 388 Participants with Virologic Failure A. Erice*1, H. Ribaudo2, L. M. Demeter3, S. H. Eshleman4, S. Hammer5, N. S. Hellmann6, and M. Fischl7 for the ACTG 388 Resistance Study Team 1Univ. of Minnesota, Minneapolis; 2Harvard Univ., Boston, MA; 3Univ. of Rochester Sch. of Med. and Dentistry, NY; 4Johns Hopkins Univ., Baltimore, MD; 5Columbia Univ., New York, NY; 6ViroLogic, Inc., South San Francisco, CA; and 7Univ. of Miami, FL Background: ACTG 388 was a randomized study comparing 3TC+ZDV with IDV, EFV+IDV, or NFV+IDV in HIV-infected subjects with < 200 CD4 cells/mm3 or HIV RNA > 80,000 copies/mL, and no previous or limited antiretroviral therapy. A lower rate of virologic failure was seen with EFV+IDV (p=0.04), and a higher rate with NFV+IDV (p=0.06) than with IDV. Methods: HIV resistance was analyzed in plasma obtained at baseline and virologic failure. Phenotypic resistance was measured using the PhenoSense assay (ViroLogic). Genotypic resistance was determined in three ACTG laboratories using the Applied Biosystems ViroSeqTM HIV-1 Genotyping System. Resistance mutations were defined according to the IAS-USA update on Drug Resistance Mutations in HIV (http://www.iasusa.org). Results: Phenotypic resistance results were obtained from 116 baseline and 97 failure time points. HIV with a fully susceptible phenotype was found in 105 (91%) subjects at baseline and in 38 (39%) at failure (IDV: 22%; EFV+IDV: 24%; NFV+IDV; 55%; p = 0.005). HIV with a 3TC-resistant phenotype was found at failure in 49 (51%) subjects (IDV: 78%; EFV+IDV: 33%; NFV+IDV: 43%). HIV with an EFV-resistant phenotype was found in 13 (13%) subjects at failure (12 with EFV+IDV). Genotypic resistance data were obtained from 113 baseline and 69 failure time points. Wild-type HIV was found in 106 (94%) subjects at baseline and in 26 (38%) at failure. Mutations in HIV reverse transcriptase at codon 184 were found at failure in 35 (51%) subjects, and at codons 103/188 in 10 (14%) subjects (all with EFV+IDV). No baseline primary resistance mutations in HIV protease were seen; secondary mutations were common at baseline and remained largely unchanged at failure. Conclusions: The frequencies of phenotypic (9%) and genotypic (6%) resistance at baseline were low. At failure, 3TC resistance was common across all regimens. Drug-sensitive virus at failure was more common with NFV+IDV, suggesting other factors as the cause of virologic failure in this arm. Resistance to protease inhibitors was uncommon.

©2002 9th Conference on Retroviruses and Opportunistic Infections