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Session 61 Poster Session Antiretroviral Chemotherapy in Previously Treated Individuals Session Time: 4:30-6:30 pm Room 4E-F

414-W. Final 48-Week Genotypic and Phenotypic Analyses of Study 907: Tenofovir DF (TDF) Added to Stable Background Regimens N. A. Margot, A. Johnson, A. Cheng, D. F. Coakley, and M. D. Miller* Gilead Sci., Inc., Foster City, CA Background: Study 907 was a phase III study evaluating TDF when added to stable background regimens in treatment-experienced patients. The first 24 weeks were placebo-controlled (2:1), followed by 24 weeks of open-label TDF. 94% of patients had baseline NRTI resistance mutations. At week 24, there was a significant mean HIV RNA log10 reduction of -0.61 relative to placebo that was durable through week 48. Methods: 274/552 patients were randomly assigned to a virology substudy. Plasma HIV RT and protease were genotyped and phenotyped (Virco) at baseline, week 24, and week 48. Results: Week 48 genotypic results were obtained for 145/274 patients (53%). 58 patients (21%) developed >1 NRTI mutation; 47 of whom developed thymidine analog mutations (TAMs). Mutation development during the open-label phase was similar to placebo during the first 24 weeks (22%), suggesting that most mutations resulted from background therapy. As a group, patients who developed NRTI mutations showed continued viral load suppression (mean -0.56 log10 DAVG48). 8 patients (3%) developed the tenofovir-associated K65R mutation (5 prior, 3 after week 24). Patients developing K65R showed a wide range of responses with 3 patients maintaining viral load suppression. Week 48 phenotypic analyses showed HIV from K65R patients remained fully susceptible to AZT and d4T and had variable susceptibility to other drugs. Phenotypic data reflecting TDF exposure of 24 (n=12) to 48 (n=47) weeks were analyzed. Overall, the mean change in TDF susceptibility was 1.3-fold from baseline. 4/59 patients showed >3-fold decreased TDF susceptibility: 3 of these remained within normal TDF range (3-fold of wild-type) due to baseline TDF hypersusceptibility and 1 had reduced TDF susceptibility along with K65R. 8 of 41 substudy patients who entered the open-label phase with HIV RNA <50 copies/mL were >500 copies/mL at week 48. Most showed genotypic resistance to agents in their regimen but none developed K65R and no phenotypic resistance to TDF was observed. Conclusions: Development of most NRTI mutations in patients adding TDF to their background regimen is due to the background regimen and not associated with loss of HIV RNA suppression. The incidence of K65R through week 48 remained low (3%) and does not correlate with treatment failure. Treatment failure was associated with resistance to other agents in the regimen. Reduction in TDF susceptibility was rare in patients with up to 48 weeks of TDF exposure.

©2002 9th Conference on Retroviruses and Opportunistic Infections