Background: Among patients with multidrug-resistant human immunodeficiency virus type 1 (HIV-1) infection, salvage regimens including enfuvirtide have demonstrated sustained efficacy. Because of reluctance to use subcutaneous injections, raltegravir may be an alternative to replace enfuvirtide within a suppressive regimen. We conducted a prospective, randomized, open-label trial to compare the antiviral efficacy and safety of a switch to raltegravir with the efficacy and safety of continuing enfuvirtide.
Methods: A total of 170 patients with multidrug-resistant HIV-1 infection and plasma HIV-1 RNA levels <400 copies/mL who were receiving enfuvirtide-based regimens were randomized 1:1 to maintain enfuvirtide or to switch to raltegravir. The primary efficacy end point was the cumulative proportion of patients with virologic failure, defined as a confirmed plasma HIV-1 RNA level >or=400 copies/mL, over 24 weeks. The secondary end points mainly involved safety.
Results: The switch to raltegravir was non-inferior to the maintenance of enfuvirtide, with virologic failure rates of 1.2% in both treatment arms in the intention-to-treat analysis (beta = 0.01%; 95% confidence interval, -6.7 to 6.8) and 1.2% and 0%, respectively, in the on-treatment analysis (beta = 1.22%; 95% confidence interval, -5.6 to 8.1). At week 24, 88%-89% of patients in both arms had plasma HIV-1 RNA levels <50 copies/mL. No significant CD4 cell count changes occurred in either arm. Grade 3-4 adverse events and laboratory abnormalities were uncommon and were not different between the treatment arms.
Conclusion: A switch to raltegravir was safe, well tolerated, and virologically non-inferior to the maintenance of enfuvirtide in patients infected with multidrug-resistant HIV-1 infection who were receiving suppressive antiretroviral therapy.
Clinical trials registration: NCT00454337