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.
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.
Authors: Christa R Nevin; Jiatao Ye; Inmaculada Aban; Michael J Mugavero; David Jackson; Hui-Yi Lin; Jeroan Allison; James L Raper; Michael S Saag; James H Willig Journal: AIDS Res Hum Retroviruses Date: 2011-03-21 Impact factor: 2.205
Authors: Jean B Nachega; Vincent C Marconi; Gert U van Zyl; Edward M Gardner; Wolfgang Preiser; Steven Y Hong; Edward J Mills; Robert Gross Journal: Infect Disord Drug Targets Date: 2011-04
Authors: Steven G Deeks; Stephen J Gange; Mari M Kitahata; Michael S Saag; Amy C Justice; Robert S Hogg; Joseph J Eron; John T Brooks; Sean B Rourke; M John Gill; Ronald J Bosch; Constance A Benson; Ann C Collier; Jeffrey N Martin; Marina B Klein; Lisa P Jacobson; Benigno Rodriguez; Timothy R Sterling; Gregory D Kirk; Sonia Napravnik; Anita R Rachlis; Liviana M Calzavara; Michael A Horberg; Michael J Silverberg; Kelly A Gebo; Margot B Kushel; James J Goedert; Rosemary G McKaig; Richard D Moore Journal: Clin Infect Dis Date: 2009-11-15 Impact factor: 9.079
Authors: Brett D Shepard; Mona R Loutfy; Janet Raboud; Frank Mandy; Colin M Kovacs; Christina Diong; Michele Bergeron; Victoria Govan; Stacey A Rizza; Jonathan B Angel; Andrew D Badley Journal: J Acquir Immune Defic Syndr Date: 2008-06-01 Impact factor: 3.731