title: Different impact of raltegravir versus efavirenz on CD4/CD8 ratio recovery in HIV-infected patients.
abstract: A low CD4/CD8 ratio during treated HIV identifies individuals with heightened immunoactivation and excess mortality. Whether ART regimens elicit distinct CD4/CD8 ratio recovery remains unknown. We aimed to compare the efficacy of an integrase inhibitor versus a non-nucleoside to normalize the CD4/CD8 ratio.
  
  
  
  We conducted a post hoc analysis of the STARTMRK study, a randomized, blinded, double-dummy Phase III trial of raltegravir versus efavirenz, and each in combination with tenofovir/emtricitabine, in treatment-naive HIV-infected adults. Blinding was maintained for the entire 5 year duration of the study. Kaplan-Meier methods for time-dependent variables were used to calculate the rates of CD4/CD8 normalization at different cut-offs and cumulative probabilities. Cox proportional hazard models were used to compare probabilities of CD4/CD8 normalization by treatment arm.
  
  
  
  A total of 563 patients were analysed; 81% were males and the mean age (SD) was 37 (10) years. Raltegravir was associated with higher rates of CD4/CD8 ratio normalization at the >0.4 cut-off (median time to normalization = 56 versus 84 days; P = 0.048 by log-rank test). A Cox proportional hazard model stratified based on baseline CD4 counts showed an association between raltegravir and higher rates of CD4/CD8 ratio normalization (HR = 1.23; P = 0.02).
  
  
  
  We herein show that normalization of the CD4/CD8 ratio above a clinically meaningful threshold may be dependent on the drug class used. Raltegravir showed faster CD4/CD8 ratio normalization compared with efavirenz, a finding with potential clinical implications. Whether other integrase inhibitors have a similar impact for this outcome remains to be explored.
authors.affiliation: Department of Infectious Diseases, Hospital Universitario Ramón y Cajal, Facultad de Medicina, Universidad de Alcalá (IRYCIS), Madrid, Spain sergio.serrano@salud.madrid.org.
authors.forename: Sergio
authors.initials: S
authors.lastname: Serrano-Villar
authors.affiliation: Merck, North Wales, PA 19454, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Merck, North Wales, PA 19454, USA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Rodgers
authors.affiliation: Department of Infectious Diseases, Hospital Universitario Ramón y Cajal, Facultad de Medicina, Universidad de Alcalá (IRYCIS), Madrid, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Moreno
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D048588:Benzoxazines / Q000627:therapeutic use*; D016516:CD4-CD8 Ratio; D003521:Cyclopropanes; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D000068898:Raltegravir Potassium / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D000068898:Raltegravir Potassium; C098320:efavirenz