Long-Term Efficacy and Safety of the HIV Integrase Inhibitor Raltegravir in Patients With Limited Treatment Options in a Phase II Study

Background: Raltegravir in combination therapy has demonstrated potent suppression of HIV-1 with a favorable safety profile. This report provides 96-week efficacy and safety data from Protocol 005, a Phase II study. Methods: HIV-infected patients with very limited treatment options and failing antiretroviral therapy were randomized to raltegravir 200, 400, or 600 mg or placebo b.i.d., plus optimized background therapy for >= 24 weeks; all patients were then offered open-label raltegravir 400 mg b.i.d. Efficacy measurements included changes in viral load and CD4 count from baseline and percent of patients with HIV-1 RNA < 400 and < 50 copies/mL. Results: One hundred and thirty-three patients received raltegravir and 45 received placebo. No dose-dependent differentiation in the safety or antiviral activity of raltegravir was observed during the double-blind phase. For the combined raltegravir groups, mean change in viral load from baseline was -1.60 log(10) copies/mL at week 48 and -1.38 log(10) copies/mL at week 96 (observed failure approach). At week 48, HIV-1 RNA levels were < 400 copies/mL in 68% of raltegravir recipients and < 50 copies/mL in 55%; these levels were maintained in 55% and 48% of raltegravir recipients, respectively, at week 96 (noncompleter = failure). There were few discontinuations of raltegravir (4%) due to adverse events. Conclusions: In patients with limited treatment options, raltegravir with OBT had a potent and sustained antiretroviral effect and was generally well tolerated through 96 weeks.