Raltegravir with optimized background therapy for resistant HIV-1 infection.

Adolescent; Adult; Aged; CD4 Lymphocyte Count; Double-Blind Method; Drug Resistance, Viral; Drug Therapy, Combination; Female; Follow-Up Studies; HIV Infections/drug therapy; HIV Integrase Inhibitors/adverse effects/therapeutic use; HIV-1/genetics/isolation & purification; Humans; Logistic Models; Male; Middle Aged; Neoplasms/etiology; Organic Chemicals/adverse effects/therapeutic use; Pyrrolidinones; RNA, Viral/blood; Treatment Outcome; Viral Load

Abstract :

[en] 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.)

Disciplines :

Immunology & infectious disease

Author, co-author :

Steigbigel, Roy T

Cooper, David A

Kumar, Princy N

Eron, Joseph E

Schechter, Mauro

Markowitz, Martin

Loutfy, Mona R

Lennox, Jeffrey L

Gatell, Jose M

Rockstroh, Jurgen K

More authors (19 more)

Other collaborator :

Moutschen, Michel ; Université de Liège - ULiège > Département des sciences cliniques > Immunopathologie - Transplantation

Language :

English

Title :

Raltegravir with optimized background therapy for resistant HIV-1 infection.

Publication date :

2008

Journal title :

New England Journal of Medicine

ISSN :

0028-4793

eISSN :

1533-4406

Publisher :

Massachusetts Medical Society, Waltham, United States - Massachusetts

Volume :

359

Issue :

Pages :

339-54

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 08 January 2009

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Scopus citations^®

643

Scopus citations^®
without self-citations

528

OpenCitations

533

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