title: Multiple drug class-wide resistance associated with poorer survival after treatment failure in a cohort of HIV-infected patients.
abstract: OBJECTIVE
  To evaluate the effect of drug class-wide resistance (CWR) on survival in HIV-infected individuals who underwent genotypic resistance test after antiretroviral failure.
  
  
  METHODS
  Observational, longitudinal cohort study.
  
  
  METHODS
  HIV-infected individuals experiencing treatment failure were enrolled at first genotypic resistance test. End-points were death for any cause, AIDS-related death and AIDS-defining event/death. CWR was defined according to the International AIDS Society consensus. Survival analysis was performed with Cox's model.
  
  
  RESULTS
  Among 623 patients enrolled and followed for a median of 19 months (interquartile range, 12-29), Kaplan-Meier analyses for end-points at 48 months in patients with no CWR, one CWR, two CWR or three CWR were 8.9, 11.7, 13.4 and 27.1%, respectively, for death; 6.1, 9.9, 13.4 and 21.5%, respectively, for AIDS-related death; and 16.0, 17.7, 19.3 and 35.9%, respectively, for new AIDS event/death. In a multivariate Cox's model, higher HIV RNA level, previous AIDS and detection of three CWR (hazard ratio, 5.34; 95% confidence interval, 1.76-16.24) were all significantly associated with increased risk of death, while higher CD4 cell count and use of a new boosted protease inhibitor drug after identifying genotypic resistance were associated with reduced risk. Detection of three CWR was also significantly associated with higher risk of AIDS-related death and new AIDS event/death.
  
  
  CONCLUSIONS
  Even in the late era of highly effective antiretroviral treatments, detection of CWR, particularly if extended to all three drug classes is related to poorer clinical outcome and represents a risk-marker of disease progression and death.
authors.affiliation: Clinical Department bLaboratory of Antiviral Drug Monitoring, National Institute of Infectious Diseases Lazzaro Spallanzani, IRCCS, Rome, Italy. zaccarelli@inmi.it
authors.forename: Mauro
authors.initials: M
authors.lastname: Zaccarelli
authors.forename: Valerio
authors.initials: V
authors.lastname: Tozzi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Lorenzini
authors.forename: Maria P
authors.initials: MP
authors.lastname: Trotta
authors.forename: Federica
authors.initials: F
authors.lastname: Forbici
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Visco-Comandini
authors.forename: Caterina
authors.initials: C
authors.lastname: Gori
authors.forename: Pasquale
authors.initials: P
authors.lastname: Narciso
authors.forename: Carlo F
authors.initials: CF
authors.lastname: Perno
authors.forename: Andrea
authors.initials: A
authors.lastname: Antinori
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D018432:Drug Resistance, Multiple / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016019:Survival Analysis; D017211:Treatment Failure