title: Similar efficacy of raltegravir when used with or without a protease inhibitor in treatment-experienced patients.
abstract: BACKGROUND
  Patients with multiclass-resistant HIV-1 have limited treatment options. Raltegravir, an inhibitor of integrase, has shown excellent efficacy when used with protease inhibitors (Pis) in patients with drug-resistant HIV-1. Limited data are available however about the outcomes when using raltegravir without Pis in this population.
  
  
  METHODS
  Medical records of subjects who received raltegravir as part of the Merck EAP study 0518 were reviewed and abstracted at participating sites. Eligibility criteria included HIV positivity, age ≥ 16 years, limited or no treatment options due to resistance or intolerance to multiple antiretroviral regimens, detectable viremia on current treatment regimen, and documented resistance to at least one drug in each antiretroviral class (PI, NNRTI, and nucleoside analogue). Demographic, clinical, and laboratory data were collected locally using a standardized collection form. Genotypic susceptibility scores (GSS) were determined from the most recent genotypic resistance test available prior to the initiation of raltegravir. The main objective was to compare virologic results in patients who received raltegravir with a PI versus those who received raltegravir without a PI.
  
  
  RESULTS
  Four hundred forty-two subjects were evaluated from the respective sites in the EAP trial, of whom 340 were evaluable. The baseline mean HIV RNA was 4.6 log copies/ mL, and the mean CD4 cell count was 159 cells/μL. The median number of total and new antiretroviral agents in the background regimen was 4 and 2, respectively. Among the 254 patients who received a PI, the most common PI used was darunavir (89%). Etravirine was commonly used in both groups: 39% of the PI group and 67% of the non-PI group. At week 12, 67% of PI patients and 64% of non-PI patients achieved HIV RNA <75 copies/mL and 85% and 86%, respectively, achieved HIV RNA <400 copies/mL GSS, which was similar in both groups at baseline, predicted achieving an HIV RNA of <400 and 75 copies/mL at week 12 (P < .05).
  
  
  CONCLUSIONS
  In treatment-experienced patients, the combination of raltegravir with a regimen not containing a PI (used with etravirine in two-thirds of patients) had similar virologic activity when compared to more standard regimens using raltegravir with a PI. The main determinant of efficacy was the number of active drugs as measured by GSS. These data expand the potential utility of raltegravir in patients with multidrug-resistant HIV.
authors.affiliation: Division of Infestious Diseases, Baystate Medical Center, Springfield, Massachusetts 01199, USA. daniel.skiest@bhs.org
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Skiest
authors.forename: Calvin
authors.initials: C
authors.lastname: Cohen
authors.forename: Karam
authors.initials: K
authors.lastname: Mounzer
authors.forename: Zach
authors.initials: Z
authors.lastname: Haigney
authors.forename: David
authors.initials: D
authors.lastname: Barker
authors.forename: Michael
authors.initials: M
authors.lastname: Gottlieb
authors.forename: Paul C
authors.initials: PC
authors.lastname: Bellman
authors.forename: Edwin
authors.initials: E
authors.lastname: Dejesus
authors.forename: Homayoon
authors.initials: H
authors.lastname: Khanlou
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Ruane
authors.forename: Chiu-Bin
authors.initials: CB
authors.lastname: Hsiao
authors.forename: Kenneth
authors.initials: K
authors.lastname: Abriola
authors.forename: Bruce
authors.initials: B
authors.lastname: Rashbaum
authors.forename: Nicholaos
authors.initials: N
authors.lastname: Bellos
authors.forename: Douglas
authors.initials: D
authors.lastname: Ward
authors.forename: Amy
authors.initials: A
authors.lastname: Colson
authors.forename: Frances
authors.initials: F
authors.lastname: Santiago
authors.forename: Anne
authors.initials: A
authors.lastname: Habel
authors.forename: Jane
authors.initials: J
authors.lastname: Garb
mesh_terms: D018791:CD4 Lymphocyte Count; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D019428:HIV Integrase Inhibitors / Q000627:therapeutic use*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000627:therapeutic use*; D012367:RNA, Viral / Q000032:analysis; D000068898:Raltegravir Potassium
chemical_list: D019428:HIV Integrase Inhibitors; D017320:HIV Protease Inhibitors; D011760:Pyrrolidinones; D012367:RNA, Viral; D000068898:Raltegravir Potassium