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

416-W. Safety Profile of Tenofovir DF in Antiretroviral-Experienced Patients from Randomized, Double-Blind, Placebo-Controlled Clinical Trials A. Cheng*, S. Barriere, D. F. Coakley, S. S. Chen, M. Wulfsohn, and J. J. Toole Gilead Sci., Inc., Foster City, CA Background: Tenofovir DF (TDF) is a single-tablet once-daily nucleotide reverse transcriptase inhibitor (NRTI) with activity against wild type and nucleoside resistant HIV. Methods: Adverse event (AE) and laboratory data were pooled and analyzed from 2 phase 2-3 studies in antiretroviral-experienced patients (mean duration prior therapy: > 5 years): 443 patients who received TDF 300 mg and 210 patients who received matching placebo (PLB) during the 24-week double-blind periods of the studies. Including crossovers from PLB to TDF, a total of 687 patients received TDF 300 mg. Extended-dosing periods were also assessed for safety and tolerability of TDF in the 687 patients (mean total duration: 58 weeks; maximum 143 weeks). Results: During the initial 24 weeks, the severity and incidence of AE and laboratory abnormalities (LA), as well as the incidence of therapy discontinuations for AE (3%) were similar between the PLB and TDF groups. A slightly higher incidence of mild to moderate gastrointestinal Aes were reported in the TDF group compared to PLB, such as nausea (20% vs 15%), diarrhea (22% vs 17%), and vomiting (12% vs 6%). However, only 1% of patients discontinued treatment due to gastrointestinal adverse events. The incidence of serious adverse events (4%) was slightly less than that reported in the PLB group (7%). During the extended dosing periods of the studies, the incidence of AE and LA increased slightly, but remained similar to that observed with placebo during the initial 24 weeks. Serum creatinine elevations and hypophosphatemia occurred sporadically, were transient in nature and resolved without interruption of treatment. No patient discontinued TDF for increase in serum creatinine or hypophosphatemia. Finally, no evidence of TDF-related bone marrow or mitochondrial toxicity (e.g. anemia, neutropenia, neuropathy, pancreatitis, lactic acidosis) or effects on lipid metabolism have been detected. Conclusions: In the placebo-controlled phase 2-3 studies of tenofovir DF conducted to date, the severity and incidence of AE and LA, as well as the proportion of patients discontinuing tenofovir DF, were similar to placebo.

©2002 9th Conference on Retroviruses and Opportunistic Infections