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

Association of heterozygous CCR5Δ32 deletion with survival in HIV-infection: A cohort study.
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Ruiz-Mateos E, Tarancon-Diez L, Alvarez-Rios AI, Dominguez-Molina B, Genebat M, Pulido I, Abad MA, Muñoz-Fernandez MA, Leal M,


Ruiz-Mateos E, Tarancon-Diez L, Alvarez-Rios AI, Dominguez-Molina B, Genebat M, Pulido I, Abad MA, Muñoz-Fernandez MA, Leal M, (click to view)

Ruiz-Mateos E, Tarancon-Diez L, Alvarez-Rios AI, Dominguez-Molina B, Genebat M, Pulido I, Abad MA, Muñoz-Fernandez MA, Leal M,

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Antiviral research 2017 12 05() pii 10.1016/j.antiviral.2017.12.002

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 = 95, 40.6%) and non-AIDS (n = 97, 41.5%) events were the main causes of 234 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.

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