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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.    Design  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.

Risk of All-Cause Mortality in HIV Infected Patients Is Associated with Clinical, Immunologic Predictors and the CCR5 Δ32 Deletion