title: Raltegravir with optimized background therapy for resistant HIV-1 infection.
abstract: 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.)
authors.affiliation: State University of New York at Stony Brook, Stony Brook, USA.
authors.forename: Roy T
authors.initials: RT
authors.lastname: Steigbigel
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
authors.forename: Princy N
authors.initials: PN
authors.lastname: Kumar
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Eron
authors.forename: Mauro
authors.initials: M
authors.lastname: Schechter
authors.forename: Martin
authors.initials: M
authors.lastname: Markowitz
authors.forename: Mona R
authors.initials: MR
authors.lastname: Loutfy
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Lennox
authors.forename: Jose M
authors.initials: JM
authors.lastname: Gatell
authors.forename: Jurgen K
authors.initials: JK
authors.lastname: Rockstroh
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
authors.forename: Patrick
authors.initials: P
authors.lastname: Yeni
authors.forename: Adriano
authors.initials: A
authors.lastname: Lazzarin
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Joshua
authors.initials: J
authors.lastname: Chen
authors.forename: Desmond M
authors.initials: DM
authors.lastname: Ryan
authors.forename: Rand R
authors.initials: RR
authors.lastname: Rhodes
authors.forename: John A
authors.initials: JA
authors.lastname: Killar
authors.forename: Lucinda R
authors.initials: LR
authors.lastname: Gilde
authors.forename: Kim M
authors.initials: KM
authors.lastname: Strohmaier
authors.forename: Anne R
authors.initials: AR
authors.lastname: Meibohm
authors.forename: Michael D
authors.initials: MD
authors.lastname: Miller
authors.forename: Daria J
authors.initials: DJ
authors.lastname: Hazuda
authors.forename: Michael L
authors.initials: ML
authors.lastname: Nessly
authors.forename: Mark J
authors.initials: MJ
authors.lastname: DiNubile
authors.forename: Robin D
authors.initials: RD
authors.lastname: Isaacs
authors.forename: Bach-Yen
authors.initials: BY
authors.lastname: Nguyen
authors.forename: Hedy
authors.initials: H
authors.lastname: Teppler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D004311:Double-Blind Method; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy*; D019428:HIV Integrase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000209:etiology; D009930:Organic Chemicals / Q000009:adverse effects / Q000627:therapeutic use*; D011760:Pyrrolidinones; D012367:RNA, Viral / Q000097:blood; D000068898:Raltegravir Potassium; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019428:HIV Integrase Inhibitors; D009930:Organic Chemicals; D011760:Pyrrolidinones; D012367:RNA, Viral; D000068898:Raltegravir Potassium