Background: Resistance to antiretroviral agents remains a lead- ing cause of treatment failure for patients infected with HIV-1.

Results: A statistically significant decrease in HIV-1 RNA level through week 24 (the primary end point) was observed in the tenofovir DF group versus the placebo group (0.61 log10 copies/mL vs. 0.03 log10 copies/mL, respectively [P < 0.001]; difference, 0.58 log10 copies/mL [95% CI, 0.68 to 0.49 log10 copies/mL]). In a virologic substudy, 94% of 253 patients had plasma isolates expressing reverse transcriptase mutations associated with nucleoside resistance mutations at baseline. Through week 24, the incidence of clinical adverse events was similar between patients receiving placebo and those receiving tenofovir DF (14% vs. 13%). No evidence of tenofovir DF–related toxicity was seen through week 48. Conclusion: In treatment-experienced patients with suboptimal viral suppression, tenofovir DF significantly reduced HIV-1 RNA level and had a safety profile similar to that of placebo.