Relationship between CCR5(WT/Δ32) heterozygosity and HIV-1 reservoir size in adolescents and young adults with perinatally acquired HIV-1 infection

Background: Several host factors contribute to human immunodeficiency virus (HIV) disease progression in the absence of combination antiretroviral therapy (cART). Among them, the CC-chemokine receptor 5 (CCR5) is known to be the main co-receptor used by HIV-1 to enter target cells during the early stages of an HIV-1 infection. Objective: We evaluated the association of CCR5((WT/Delta 32)) heterozygosity with HIV-1 reservoir size, lymphocyte differentiation, activation and immunosenescence in adolescents and young adults with perinatally acquired HIV infection receiving cART. Methods: CCR5 genotype was analysed in 242 patients with vertically transmitted HIV-1 infection from Paediatric Spanish AIDS Research Network Cohort (coRISpe). Proviral HIV-1 DNA was quantified by digital-droplet PCR, and T-cell phenotype was evaluated by flow cytometry in a subset of 24 patients (ten with CCR5((Delta 32/WT)) genotype and 14 with CCR5((WT/WT)) genotype). Results: Twenty-three patients were heterozygous for the Delta 32 genotype but none was homozygous for the mutated CCR5 allele. We observed no difference in the HIV-1 reservoir size (455 and 578 copies of HIV-1 DNA per million CD4(+) T cells in individuals with CCR5((WT/WT)) and CCR5((Delta 32/WT)) genotypes, respectively; p 0.75) or in the immune activation markers between both genotype groups. However, we found that total HIV-1 DNA in CD4(+) T cells correlated with the percentage of memory CD4(+) T cells: a direct correlation in CCR5((WT/Delta 32)) patients but an inverse correlation in those with the CCR5((WT/WT)) genotype. Conclusions: This finding suggests a differential distribution of the viral reservoir compartment in CCR5((WT/Delta 32)) patients with perinatal HIV infection, which is a characteristic that may affect the design of strategies for reservoir elimination. M. Martinez-Bonet, Clin Microbiol Infect 2017;23:318 (C) 2017 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).