title: Risk of all-cause mortality in HIV infected patients is associated with clinical, immunologic predictors and the CCR5 Δ32 deletion.
abstract: OBJECTIVE
  Investigation of the interplay between the CCR5 Δ32/wt genotype and demographic, epidemiological, clinical and immunological factors associated with mortality in the cART era.
  
  
  METHODS
  Longitudinal data from 507 HIV-infected patients following the Δ32 allele detection were analyzed.
  
  
  METHODS
  Cumulative 15 years mortality was calculated using Kaplan-Meyer methodology. Hazard ratios were estimated using univariate Cox models. Basing on Akakie information criteria and statistical significance multivariate Cox model was constructed and effect plots presenting adjusted hazard ratio time-dependency were drawn. Analysis of the association of all-cause mortality and CCR5 Δ32/wt genotype prior to the antiretroviral treatment (cART) initiation (n = 507) and on the therapy (n = 422) was also performed.
  
  
  RESULTS
  A mortality rate of 2.66 (CI 2.57-3.19) per 100 person-years was observed. Univariate analysis factors modifying the risk of death included the CCR5 genotype, gender, history of cART, AIDS diagnosis and also CD4 lymphocyte nadir, zenith, the latest CD4 count and stable levels >500 cells/µl. For multivariate analysis the following predictors were selected: CCR5 genotype (HR for wt/wt 2.53, CI 1.16-5.53, p = 0.02), gender (HR for males 1.91, 95%CI 1.1-3.36, p = 0.023), introduction of combined antiretroviral treatment (HR 4.85, CI 3.0-7.89, if untreated or treated <1 month, p<0.0001) CD4 count of 500 cells/µl for six months or more (HR 4.16, CI 1.95-8.88 if not achieved, p = 0.028), the latest CD4 count (HR 5.44, CI 3.39-8.74 for <100 cells/µl, p<0.0001) and history of AIDS (HR 1.69, CI 1.03-2.79, p = 0.039). Among untreated individuals the Δ32/wt genotype was associated with notably better survival (p = 0.026), while among cART treated individuals the Δ32 mutation did not correlate significantly with higher survival rates (p = 0.23).
  
  
  CONCLUSIONS
  The Δ32 CCR5 allele is associated with a reduction of the risk of all-cause mortality in HIV (+) patients alongside clinical and immunologic predictors such as AIDS, history of cART, lymphocyte CD4 cell count and gender.
authors.affiliation: Department of Infectious Diseases and Hepatology, Pomeranian Medical University, Szczecin, Poland. mparczewski@yahoo.co.uk
authors.forename: Milosz
authors.initials: M
authors.lastname: Parczewski
authors.forename: Dorota
authors.initials: D
authors.lastname: Bander
authors.forename: Magdalena
authors.initials: M
authors.lastname: Leszczyszyn-Pynka
authors.forename: Anna
authors.initials: A
authors.lastname: Urbanska
authors.forename: Mariusz
authors.initials: M
authors.lastname: Kaczmarczyk
authors.forename: Andrzej
authors.initials: A
authors.lastname: Ciechanowicz
authors.forename: Anna
authors.initials: A
authors.lastname: Boron-Kaczmarska
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology / Q000401:mortality; D000328:Adult; D002423:Cause of Death; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000401:mortality*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D015999:Multivariate Analysis; D011044:Poland / Q000453:epidemiology; D011379:Prognosis; D016016:Proportional Hazards Models; D019713:Receptors, CCR5 / Q000235:genetics*; D012307:Risk Factors; D017384:Sequence Deletion
chemical_list: D019713:Receptors, CCR5