title: Association of HIV-1 replication capacity with treatment outcomes in patients with virologic treatment failure.
abstract: BACKGROUND
  The extent to which HIV-1 replication capacity (RC) influences the response to therapy remains to be established.
  
  
  METHODS
  Phenotypic susceptibility and RC of baseline isolates (n = 139) from patients enrolled in the ARGENTA trial were measured and correlated to treatment outcomes over 36 months.
  
  
  RESULTS
  RC in baseline isolates correlated with the number of phenotypically active drugs (R = 0.34, P < 0.001). Crude viral RC did not predict treatment outcomes. When viral RC was adjusted by baseline CD4 cell counts, HIV-1 RNA levels, and phenotypic susceptibility to the rescue regimen, it showed significant association with the immunologic outcome (per log10 RC higher, mean difference in 36 months' time-averaged change from baseline CD4 count = -68 cells/microL; P = 0.020). In the subgroup of patients with 3 or more phenotypically active drugs in the salvage regimen (n = 35, median RC = 65%), subjects carrying isolates with RC < or =65% as compared to those with RC >65% had better time-averaged HIV-1 RNA responses (mean: -1.04 vs. -0.32 log10 copies/mL; P = 0.012) and CD4 cell responses (mean: 132 vs. -7 cells/microL; P = 0.006). Among patients with HIV-1 RNA levels persistently >500 copies/mL (n = 61), RC, on a log10 basis, was inversely associated with time-averaged 36-month CD4 cell responses (beta = -0.26; P = 0.046).
  
  
  CONCLUSIONS
  After normalizing for viral susceptibility to the employed regimen or in patient subsets with suboptimal virologic response, higher viral RC may predict worse subsequent treatment outcomes.
authors.affiliation: Institute of Clinical Infectious Diseases, Policlinoco Universitario Agostino Gemelli, Catholic University of the Sacred Heart, Largo F. Vito 1, 00168 Rome, Italy. andrea.deluca@rm.unicatt.it
authors.forename: Andrea
authors.initials: A
authors.lastname: De Luca
authors.forename: Jodi
authors.initials: J
authors.lastname: Weidler
authors.forename: Simona
authors.initials: S
authors.lastname: Di Giambenedetto
authors.forename: Eoin
authors.initials: E
authors.lastname: Coakley
authors.forename: Antonella
authors.initials: A
authors.lastname: Cingolani
authors.forename: Michael
authors.initials: M
authors.lastname: Bates
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Lie
authors.forename: Rick
authors.initials: R
authors.lastname: Pesano
authors.forename: Roberto
authors.initials: R
authors.lastname: Cauda
authors.forename: Jonathan
authors.initials: J
authors.lastname: Schapiro
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D010641:Phenotype; D012367:RNA, Viral / Q000097:blood*; D017211:Treatment Failure; D016896:Treatment Outcome; D014779:Virus Replication
chemical_list: D012367:RNA, Viral