Tenofovir DF in antiretroviral-experienced patients: results from a 48-week, randomized, double-blind study

Objective: To evaluate the safety and efficacy of once daily doses of tenofovir DF (TDF) administered in combination with other antiretroviral therapy (ART) in treatment-experienced HIV-1-infected patients with incomplete virological suppression. Design: One-hundred and eighty-nine subjects with plasma HIV-1 RNA levels between 400 and 1 00 000 copies/ml and stable ART (≥ 8 weeks) were randomized (2: 2: 2: 1 ratio) to add TDF 75 mg, 150 mg, or 300 mg or placebo to existing ART in a double-blinded manner. After 24 weeks, patients initially randomized to placebo received blinded TDF 300 mg. Methods: Efficacy was analyzed by the mean changes HIV-1 RNA levels (log 10 copies/ml plasma; DAVG xx ) from week 0 to weeks 4, 24, and 48. Safety was analyzed by incidence of grade 3 or 4 clinical and laboratory adverse events. Results: At baseline, patients had mean 4.6 years prior ART use with 94% having HIV-1 with nucleoside-associated resistance mutations. There were statistically significant decreases in DAVG 4 and DAVG 24 for all doses of TDF compared with placebo, with the greatest effect seen with TDF 300 mg (DAVG 4 , -0.62, P < 0.001; DAVG 24 , -0.58; P< 0.001; DAVG 48 , -0.62). The incidence of adverse events was similar among the TDF groups and placebo through week 24. Throughout the 48-week study, no significant changes in renal function were observed. Conclusions: In treatment-experienced patients with baseline nucleoside resistance mutations, TDF provided dose-related, durable reductions in HIV-1 RNA. Through 24 weeks, the safety profile of TDF was similar to that of placebo.