Analysis of the CCR2-64I (rs1799864) genetic polymorphism distribution and its effect on the risk of HIV-1 infection and immunovirological outcomes in Moroccan ART-treated individuals

Background: Several studies have reported that the CCR2-64I genetic polymorphism influences the rate of markers of HIV-1 disease progression (HIV-1 viral loads and CD4+ T cell counts). However, the association between this mutation and HIV-1 infection among antiretroviral therapy (ART)-treated HIV-1 seropositive patients is controversial. In Morocco, no data is available regarding this polymorphism. Objectives: In the present case-control study, we aimed to investigate the frequency of the CCR2-64I genetic polymorphism and to evaluate the association of this mutant allele with susceptibility to HIV-1 infection and immunovirological outcomes in Morocco. Methods: We recruited 100 HIV-1 seropositive patients (cases) undergoing antiretroviral therapy (ART) and 200 HIV-1 seronegative individuals from Mohammed V Military Training Hospital in Rabat. Genotyping of the CCR2-64I polymorphism was performed using Polymerase Chain Reaction (PCR) assay and automated DNA sequencing. The comparison between variables was performed using χ2-test, Fisher's exact test, or Mann–Whitney U test, as appropriate. Factors associated with immunovirological outcomes were assessed using logistic regression analysis. Results: The frequencies of CCR2-64V/CCR2-64V, CCR2-64V/CCR2-64I and CCR2-64I/CCR2-64I genotypes were 67, 30 and 3%, respectively among HIV-1 infected patients (cases), compared to 73, 24.50, and 2.50%, respectively, among HIV-1 uninfected individuals (controls). We didn't observe any statistically significant difference in the genotype distribution between cases and control groups. Additionally, the multivariate logistic regression analysis didn't reveal a significant association between the CCR2-64I polymorphism and the immunovirological outcomes after one year of ART (p> 0.05). Conclusion: We are the first to report the frequency of CCR2-64I polymorphism and its association with HIV-1 infection in Moroccan individuals. Our findings suggest that the CCR2-64I allele may not influence the susceptibility to HIV-1 infection, as was previously reported in other populations. Besides, we hypothesize that this mutation, independently of classical risk factors, may not impact the virological outcomes and immunological recovery among HIV-1 infected patients under treatment. Nevertheless, this result required confirmation by further large scale and extended follow-up studies, considering the low frequency of the CCR2-64I/CCR2-64I homozygous genotype in our population.