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Title: Relationship between CCR5(WT/Δ32) heterozygosity and HIV-1 reservoir size in adolescents and young adults with perinatally acquired HIV-1 infection.
Authors: Martínez-Bonet, M
González-Serna, A
Clemente, M I
Morón-López, S
Díaz, L
Navarro, M
Puertas, M C
Leal, M
Ruiz-Mateos, E
Martinez-Picado, J
Muñoz-Fernández, M A
Keywords: Adolescents;CCR5((WT/Δ32));Human immunodeficiency virus-1;Reservoir size;Young adults
metadata.dc.subject.mesh: Acquired Immunodeficiency Syndrome
CD4-Positive T-Lymphocytes
Child, Preschool
DNA, Viral
Genotyping Techniques
HIV Infections
Receptors, CCR5
Retrospective Studies
Viral Load
Young Adult
Issue Date: 29-Dec-2016
Abstract: 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. 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. 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). 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. 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.
metadata.dc.identifier.doi: 10.1016/j.cmi.2016.12.020
Appears in Collections:Producción 2020

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