Risk of all-cause mortality in HIV infected patients is associated with clinical, immunologic predictors and the CCR5 Δ32 deletion.

<h4>Objective</h4>Investigation of the interplay between the CCR5 Δ32/wt genotype and demographic, epidemiological, clinical and immunological factors associated with mortality in the cART era.<h4>Design</h4>Longitudinal data from 507 HIV-infected patients following the Δ32 a...

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Autores principales:	Milosz Parczewski, Dorota Bander, Magdalena Leszczyszyn-Pynka, Anna Urbanska, Mariusz Kaczmarczyk, Andrzej Ciechanowicz, Anna Boron-Kaczmarska
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/acd45a49c6f545b1a6119e9952276799
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spelling	oai:doaj.org-article:acd45a49c6f545b1a6119e99522767992021-11-18T06:50:05ZRisk of all-cause mortality in HIV infected patients is associated with clinical, immunologic predictors and the CCR5 Δ32 deletion.1932-620310.1371/journal.pone.0022215https://doaj.org/article/acd45a49c6f545b1a6119e99522767992011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21789236/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Objective</h4>Investigation of the interplay between the CCR5 Δ32/wt genotype and demographic, epidemiological, clinical and immunological factors associated with mortality in the cART era.<h4>Design</h4>Longitudinal data from 507 HIV-infected patients following the Δ32 allele detection were analyzed.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.Milosz ParczewskiDorota BanderMagdalena Leszczyszyn-PynkaAnna UrbanskaMariusz KaczmarczykAndrzej CiechanowiczAnna Boron-KaczmarskaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 7, p e22215 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Milosz Parczewski Dorota Bander Magdalena Leszczyszyn-Pynka Anna Urbanska Mariusz Kaczmarczyk Andrzej Ciechanowicz Anna Boron-Kaczmarska Risk of all-cause mortality in HIV infected patients is associated with clinical, immunologic predictors and the CCR5 Δ32 deletion.
description	<h4>Objective</h4>Investigation of the interplay between the CCR5 Δ32/wt genotype and demographic, epidemiological, clinical and immunological factors associated with mortality in the cART era.<h4>Design</h4>Longitudinal data from 507 HIV-infected patients following the Δ32 allele detection were analyzed.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.
format	article
author	Milosz Parczewski Dorota Bander Magdalena Leszczyszyn-Pynka Anna Urbanska Mariusz Kaczmarczyk Andrzej Ciechanowicz Anna Boron-Kaczmarska
author_facet	Milosz Parczewski Dorota Bander Magdalena Leszczyszyn-Pynka Anna Urbanska Mariusz Kaczmarczyk Andrzej Ciechanowicz Anna Boron-Kaczmarska
author_sort	Milosz Parczewski
title	Risk of all-cause mortality in HIV infected patients is associated with clinical, immunologic predictors and the CCR5 Δ32 deletion.
title_short	Risk of all-cause mortality in HIV infected patients is associated with clinical, immunologic predictors and the CCR5 Δ32 deletion.
title_full	Risk of all-cause mortality in HIV infected patients is associated with clinical, immunologic predictors and the CCR5 Δ32 deletion.
title_fullStr	Risk of all-cause mortality in HIV infected patients is associated with clinical, immunologic predictors and the CCR5 Δ32 deletion.
title_full_unstemmed	Risk of all-cause mortality in HIV infected patients is associated with clinical, immunologic predictors and the CCR5 Δ32 deletion.
title_sort	risk of all-cause mortality in hiv infected patients is associated with clinical, immunologic predictors and the ccr5 δ32 deletion.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/acd45a49c6f545b1a6119e9952276799
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Risk of all-cause mortality in HIV infected patients is associated with clinical, immunologic predictors and the CCR5 Δ32 deletion.

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