title: Clinical efficacy of raltegravir against B and non-B subtype HIV-1 in phase III clinical studies.
abstract: OBJECTIVE
  We evaluated the long-term efficacy of raltegravir according to HIV-1 subtype (B and non-B) using data from three phase III studies in treatment-experienced (BENCHMRK-1 and 2) and treatment-naive (STARTMRK) HIV-infected patients.
  
  
  METHODS
  HIV-1 subtypes were identified from baseline plasma specimens using genotypic data of the PhenoSense GT test (Monogram Biosciences, South San Francisco, California, USA). Non-B subtypes were combined for the current analyses due to small numbers of each specific subtype. An observed failure approach was used (only discontinuations due to lack of efficacy were treated as failures). Resistance evaluation was performed in patients with documented virologic failure.
  
  
  RESULTS
  Seven hundred and forty-three patients received raltegravir and 519 received comparator (efavirenz in STARTMRK; optimized background therapy in BENCHMRK). Non-B subtype virus (A, A/C, A/D, A/G, A1, AE, AG, B/G, BF, C, D, D/F, F, F1, G, and complex) was isolated at baseline in 98 (13%) raltegravir recipients and 62 (12%) comparator recipients. Subtypes AE and C were most common, isolated in 41 and 43 patients, respectively. The proportion of raltegravir recipients achieving HIV RNA less than 50 copies/ml was similar between non-B and B subtypes (STARTMRK: 94.5 vs. 88.7%; BENCHMRK-1 and 2: 66.7 vs. 60.7%); change in CD4 cell count also was similar between non-B and B subtypes (STARTMRK: 243 vs. 221 cells/μl; BENCHMRK-1 and 2: 121 vs. 144 cells/μl). Phenotypic resistance to raltegravir in non-B virus was associated with integrase mutations observed previously in subtype B virus.
  
  
  CONCLUSIONS
  In phase III studies in treatment-naive and treatment-experienced patients, raltegravir showed comparable and potent clinical efficacy against B and non-B HIV-1 subtypes.
authors.affiliation: University of Bonn, Bonn-Venusberg, Germany.
authors.forename: Jürgen K
authors.initials: JK
authors.lastname: Rockstroh
authors.forename: Hedy
authors.initials: H
authors.lastname: Teppler
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Peter
authors.initials: P
authors.lastname: Sklar
authors.forename: Michael D
authors.initials: MD
authors.lastname: Miller
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Harvey
authors.forename: Kim M
authors.initials: KM
authors.lastname: Strohmaier
authors.forename: Randi Y
authors.initials: RY
authors.lastname: Leavitt
authors.forename: Bach-Yen T
authors.initials: BY
authors.lastname: Nguyen
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018791:CD4 Lymphocyte Count; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000494:pharmacology*; D000068898:Raltegravir Potassium; D016896:Treatment Outcome; D014481:United States; D019562:Viral Load; D054299:env Gene Products, Human Immunodeficiency Virus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology
chemical_list: D044966:Anti-Retroviral Agents; D011760:Pyrrolidinones; D054299:env Gene Products, Human Immunodeficiency Virus; D000068898:Raltegravir Potassium