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

570-T. M184V Selection in Suppressed Subjects at Week 24 May Not Be Associated with Treatment Outcome (NZTA4002) J. J. Eron*1, D. McClernon2, A. Pierce2, G. Sawyerr2, H. Gao2, M. St. Clair2, J. Tolson2, G. Capuano2, J. Hernandez2, and J. Snidow2 1Univ. of North Carolina, Chapel Hill and 2GlaxoSmithKline, Res. Triangle Park, NC Background: Although the M184V mutation arises in subjects failing 3TC-based HAART, it is unclear whether appearance of the M184V prior to viral rebound represents a marker for subsequent treatment failure. Methods: This was a randomized, controlled trial in HIV-1 ART-naïve subjects undergoing therapy with Combivir/nelfinavir, or Combivir plus amprenavir plus abacavir for 64 weeks. Virologic failure (VF) was defined as not achieving HIV-1 RNA < 120 copies/mL (NucliSens assay, Organon Teknika) by week 24, or RNA>120 copies/mL on 2 consecutive occasions after initial response. Treatment failure included VF and withdrawals due to adverse events. For this sub-study, protease and reverse transcriptase sequence was obtained from subjects with HIV-1 RNA < 120 copies/mL at week 24. Genotypic analysis was performed by the Trugene assay. Adherence was measured via the Patient Medication Assessment Questionnaire (PMAQ). Fisher's exact test was used to compare proportions, and exact confidence intervals for the difference in proportions were constructed using StatXact. Results: Sequence was obtained from 69% (71/103) and 63% (48/76) of subjects on the 3- and 4-drug regimens, respectively. All but 1 subject did not have M184V at baseline but M184V was identified in 22% (26/119) of subjects at week 24. Of these 26, 12 (46%) subsequently failed therapy compared with 28 of 93 (30%) without the M184V at week 24. The difference was not statistically significant (95% CI from -6% to 41%, p=0.160). When only virologic failures were considered, 31% (8/26) with M184V failed compared with 24% (22/93) without M184V (CI -13-32%, p=0.455). No association was found between the presence of the M184V mutation at week 24 and self-reports of adherence at week 4, 12, and 24 (p=0.351, 0.784, and 0.940), nor was there any association between presence of the M184V mutation at week 24 and treatment (p=0.825). Self-reports of missing therapy after week 24 was not associated with treatment failure (p=0.657). Conclusions: These data suggest no association between presence of the M184V at week 24 and subsequent treatment outcome. Evolution of resistance mutations occurred in this population despite "suppressive" therapy.

©2002 9th Conference on Retroviruses and Opportunistic Infections