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

• Published in: Antiviral research 2018-02, Vol.150, p.15-19
• Main Authors: Ruiz-Mateos, Ezequiel, Tarancon-Diez, Laura, Alvarez-Rios, Ana I., Dominguez-Molina, Beatriz, Genebat, Miguel, Pulido, Ildefonso, Abad, Maria Antonia, Muñoz-Fernandez, Maria Angeles, Leal, Manuel
• Format: Article
• Language: English
• Subjects: CCR5; HIV-Infection; Survival
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2017.12.002

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. •CCR5Δ32 was associated with all-cause mortality in a cohort of HIV-infected patients covering 35 years of follow up.•CCR5Δ32 was associated with mortality when only AIDS and non-AIDS deaths were considered.•CCR5Δ32 was associated with all-cause mortality in patients on combined antiretroviral therapy at the long-term.