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

M. Martínez-Bonet, A. González-Serna, M. I. Clemente, S. Morón-López, L. Díaz, M. Navarro, M. C. Puertas, M. Leal, E. Ruiz-Mateos, J. Martinez-Picado, M. A. Muñoz-Fernández

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    3 Citations (Scopus)

    Abstract

    © 2017 The Authors 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/Δ32) 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(Δ32/WT) genotype and 14 with CCR5(WT/WT) genotype). Results Twenty-three patients were heterozygous for the Δ32 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(Δ32/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/Δ32) 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/Δ32) patients with perinatal HIV infection, which is a characteristic that may affect the design of strategies for reservoir elimination.
    Original languageEnglish
    Pages (from-to)318-324
    JournalClinical Microbiology and Infection
    Volume23
    Issue number5
    DOIs
    Publication statusPublished - 1 May 2017

    Keywords

    • Adolescents
    • CCR5 (WT/Δ32)
    • Human immunodeficiency virus-1
    • Reservoir size
    • Young adults

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