Raltegravir with Optimized Background Therapy for Resistant HIV-1 Infection

doi:10.1056/NEJMoa0708975

Volume 359:339-354		July 24, 2008		Number 4

Raltegravir with Optimized Background Therapy for Resistant HIV-1 Infection

Roy T. Steigbigel, M.D., David A. Cooper, M.D., D.Sc., Princy N. Kumar, M.D., Joseph E. Eron, M.D., Mauro Schechter, M.D., Ph.D., Martin Markowitz, M.D., Mona R. Loutfy, M.D., M.P.H., Jeffrey L. Lennox, M.D., Jose M. Gatell, M.D., Ph.D., Jurgen K. Rockstroh, M.D., Christine Katlama, M.D., Patrick Yeni, M.D., Adriano Lazzarin, M.D., Bonaventura Clotet, M.D., Jing Zhao, Ph.D., Joshua Chen, Ph.D., Desmond M. Ryan, B.S., Rand R. Rhodes, M.S., John A. Killar, M.S., Lucinda R. Gilde, B.S., Kim M. Strohmaier, B.S., Anne R. Meibohm, Ph.D., Michael D. Miller, Ph.D., Daria J. Hazuda, Ph.D., Michael L. Nessly, M.S., Mark J. DiNubile, M.D., Robin D. Isaacs, M.D., Bach-Yen Nguyen, M.D., Hedy Teppler, M.D., for the BENCHMRK Study Teams

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by Havlir, D. V.

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ABSTRACT

Background Raltegravir (MK-0518) is an inhibitor of human immunodeficiencyvirus type 1 (HIV-1) integrase active against HIV-1 susceptibleor resistant to older antiretroviral drugs.

Methods We conducted two identical trials in different geographicregions to evaluate the safety and efficacy of raltegravir,as compared with placebo, in combination with optimized backgroundtherapy, in patients infected with HIV-1 that has triple-classdrug resistance in whom antiretroviral therapy had failed. Patientswere 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 relatedto the study treatment in 13 of these 17 patients: 7 of the462 raltegravir recipients (1.5%) and 6 of the 237 placebo recipients(2.5%). The results of the two studies were consistent. At week16, counting noncompletion as treatment failure, 355 of 458raltegravir recipients (77.5%) had HIV-1 RNA levels below 400copies per milliliter, as compared with 99 of 236 placebo recipients(41.9%, P<0.001). Suppression of HIV-1 RNA to a level below50 copies per milliliter was achieved at week 16 in 61.8% ofthe raltegravir recipients, as compared with 34.7% of placeborecipients, and at week 48 in 62.1% as compared with 32.9% (P<0.001for both comparisons). Without adjustment for the length offollow-up, cancers were detected in 3.5% of raltegravir recipientsand in 1.7% of placebo recipients. The overall frequencies ofdrug-related adverse events were similar in the raltegravirand placebo groups.

Conclusions In HIV-infected patients with limited treatmentoptions, raltegravir plus optimized background therapy providedbetter viral suppression than optimized background therapy alonefor at least 48 weeks. (ClinicalTrials.gov numbers, NCT00293267 [ClinicalTrials.gov] and NCT00293254 [ClinicalTrials.gov] .)

Source Information

From the State University of New York at Stony Brook, Stony Brook (R.T.S.); National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney (D.A.C.); Georgetown University Medical Center, Washington, DC (P.N.K.); University of North Carolina, Chapel Hill (J.E.E.); Universidade Federal do Rio de Janeiro, Rio de Janeiro (M.S.); Aaron Diamond Research Center, Rockefeller University, New York (M.M.); University of Toronto, Toronto (M.R.L.); Emory University School of Medicine, Atlanta (J.L.L.); University of Barcelona, Barcelona (J.M.G.); University of Bonn, Bonn, Germany (J.K.R.); Hospital Pitié–Salpêtrière, Université Pierre et Marie Curie, Paris (C.K.); Hospital Bichat–Claude Bernard, Paris (P.Y.); San Raffaele Scientific Institute, Milan (A.L.); Hospital Germans Trias i Pujol, Fundación Irsicaixa, Barcelona (B.C.); and Merck Research Laboratories, North Wales, PA (J.Z., J.C., D.M.R., R.R.R., J.A.K., L.R.G., K.M.S., A.R.M., M.D.M., D.J.H., M.L.N., M.J.D., R.D.I., B.-Y.N., H.T.).

Address reprint requests to Dr. Teppler at Merck Research Laboratories, P.O. Box 1000, UG3D-56, North Wales, PA 19454-1099, or at hedy_teppler{at}merck.com.

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