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Antiviral Res. 2018 Feb;150:15-19. doi: 10.1016/j.antiviral.2017.12.002. Epub 2017 Dec 6.

Association of heterozygous CCR5Δ32 deletion with survival in HIV-infection: A cohort study.

Author information

1
Laboratory of Immunovirology, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain. Electronic address: ezequiel.ruizmateos@gmail.com.
2
Laboratory of Immunovirology, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain.
3
Department of Clinical Biochemistry, Virgen del Rocio University Hospital (IBiS/CSIC/SAS/University of Seville), Seville, Spain.
4
Molecular Immunobiology Laboratory, General Universitary Hospital Gregorio Marañon, Health Research Institute Gregorio Marañon, Spanish HIV HGM BioBank, Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
5
Laboratory of Immunovirology, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain. Electronic address: mleal@telefonica.net.

Abstract

The role of a 32 base pair deletion in the CCR5 gene (CCR5Δ32) in HIV-disease progression and response to combined antiretroviral therapy (cART) is well established. However, the impact of CCR5Δ32 in the long-term survival pre-cART and after cART introduction in a large cohort of HIV-infected patients is unknown. We analyzed the association of CCR5Δ32 deletion in the long-term survival of HIV-infected patients recruited between June 1981 and October 2016 (n = 1006). Clinical and epidemiological variables were recorded and CCR5Δ32 deletion was assessed by PCR and electrophoretic analysis. The association of CCR5Δ32 deletion with the time to death was analyzed by Log-Rank tests and Cox Regression models. The CCR5 WT/Δ32 prevalence was 13.4% (n = 135). We did not find any homozygous subject for CCR5Δ32 deletion. AIDS (n = 85, 41.5%) and non-AIDS (n = 87, 42.4%) events were the main causes of 205 deaths. CCR5Δ32 deletion was independently associated with survival (p = 0.022; hazard ratio (HR): 0.572, confidence interval (CI) [0.354-0.923]), after adjusting by HIV diagnosis before 1997, age at diagnosis, being on cART, risk of transmission, nadir CD4+ T-cell counts and CDC stage C. This result was reproduced when the analysis was restricted to patients on cART (p = 0.045; HR: 0.530 [0.286-0.985]). These results confirm the protective role of CCR5Δ32, and extend it to the long-term survival in a large cohort of HIV-infected patients. Beyond its antiviral effect, CCR5Δ32 enhanced the long-term survival of patients on cART.

KEYWORDS:

CCR5; HIV-Infection; Survival

PMID:
29221798
DOI:
10.1016/j.antiviral.2017.12.002
[Indexed for MEDLINE]

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