Multiple drug class-wide resistance associated with poorer survival after treatment failure in a cohort of HIV-infected patients

Mauro Zaccarelli, Valerio Tozzi, Patrizia Lorenzini, Maria P. Trotta, Federica Forbici, Ubaldo Visco-Comandini, Caterina Gori, Pasquale Narciso, Carlo F. Perno, Andrea Antinori

Research output: Contribution to journalArticlepeer-review

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. Design: 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.

Original languageEnglish
Pages (from-to)1081-1089
Number of pages9
JournalAIDS (London, England)
Volume19
Issue number10
Publication statusPublished - Jul 1 2005

Keywords

  • AIDS-related death
  • Drug class resistance
  • HIV resistance
  • Survival

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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