Background: Raltegravir (MK-0518) is an inhibitor of human immunodeficiency virus type 1 (HIV-1)
integrase active against HIV-1 susceptible or resistant to older antiretroviral drugs.
Methods: We conducted two identical trials in different geographic regions to evaluate the
safety and efficacy of raltegravir, as compared with placebo, in combination with
optimized background therapy, in patients infected with HIV-1 that has triple-class
drug resistance in whom antiretroviral therapy had failed. Patients were randomly
assigned to raltegravir or placebo in a 2:1 ratio.
Results: In the combined studies, 699 of 703 randomized patients (462 and 237 in the raltegravir
and placebo groups, respectively) received the study drug. Seventeen of the 699
patients (2.4%) discontinued the study before week 16. Discontinuation was related
to the study treatment in 13 of these 17 patients: 7 of the 462 raltegravir recipients
(1.5%) and 6 of the 237 placebo recipients (2.5%). The results of the two studies
were consistent. At week 16, counting noncompletion as treatment failure, 355 of
458 raltegravir recipients (77.5%) had HIV-1 RNA levels below 400 copies per milliliter,
as compared with 99 of 236 placebo recipients (41.9%, P<0.001). Suppression of
HIV-1 RNA to a level below 50 copies per milliliter was achieved at week 16 in
61.8% of the raltegravir recipients, as compared with 34.7% of placebo recipients,
and at week 48 in 62.1% as compared with 32.9% (P<0.001 for both comparisons).
Without adjustment for the length of follow-up, cancers were detected
in 3.5% of
raltegravir recipients and in 1.7% of placebo recipients. The overall frequencies of
drug-related adverse events were similar in the raltegravir and placebo groups.
Conclusions: In HIV-infected patients with limited treatment options, raltegravir plus optimized
background therapy provided better viral suppression than optimized background
therapy alone for at least 48 weeks. (ClinicalTrials.gov numbers, NCT00293267 and
NCT00293254.