Raltegravir plus optimized background therapy superior to optimized background therapy alone in treatment of resistant HIV

Key Points

Two randomized, double-blind, phase 3 clinical trials demonstrated that raltegravir plus optimized background therapy was more effective than optimized background therapy alone in suppressing resistant HIV-1. These results were published in the New England Journal of Medicine.

The ongoing Blocking Integrase in Treatment Experienced Patients With a Novel Compound Against HIV, Merck (BENCHMRK) 1 and BENCHMRK 2 studies enrolled HIV-infected patients aged ≥16 years who had HIV-1 RNA levels >1,000 copies/mL during antiretroviral therapy. Patients were required to have phenotypic or genotypic resistance to ≥1 drug in each of the 3 classes of oral antiretroviral agents. At study entry, investigators selected appropriate optimized background therapy for individual patients based on history of antiretroviral treatment, results of drug-resistance tests, and laboratory data. Patients (N=699) were randomized 2:1 to treatment with either raltegravir 400 mg twice daily or placebo plus optimized background therapy.

The prespecified primary efficacy hypothesis was that raltegravir plus optimized background therapy would demonstrate superior antiretroviral activity compared with placebo plus optimized background therapy. This efficacy analysis was to be based on the proportion of patients with HIV-1 RNA levels <400 copies/mL after 16 weeks of therapy.

In an analysis that considered any noncompletion as treatment failure, HIV-1 RNA levels were suppressed to <400 copies/mL at Week 48 in 72.3% of raltegravir-treated patients and 37.1% of placebo-treated patients (P<.001 for each study individually and for the combined studies); HIV-1 RNA levels were suppressed to <50 copies/mL at Week 48 in 62.1% of raltegravir-treated patients and 32.9% of placebo-treated patients (P<.001 for each study individually and for the combined studies).

The frequency of adverse events was generally similar between the raltegravir and placebo groups. Cancer was detected in 3.5% of raltegravir-treated patients versus 1.7% of placebo-treated patients (RR=1.54; 95% CI, 0.50–6.34).

SOURCE

Steigbigel RT, Cooper DA, Kumar PN, et al; for the BENCHMRK Study Teams. Raltegravir with optimized background therapy for resistant HIV-1 infection. N Engl J Med. 2008;359:339–354.