RT Journal Article
T1 Relationship between CCR5(WT/Δ32) heterozygosity and HIV-1 reservoir size in adolescents and young adults with perinatally acquired HIV-1 infection.
A1 Martínez-Bonet, M
A1 González-Serna, A
A1 Clemente, M I
A1 Morón-López, S
A1 Díaz, L
A1 Navarro, M
A1 Puertas, M C
A1 Leal, M
A1 Ruiz-Mateos, E
A1 Martinez-Picado, J
A1 Muñoz-Fernández, M A
K1 Adolescents
K1 CCR5((WT/Δ32))
K1 Human immunodeficiency virus-1
K1 Reservoir size
K1 Young adults
AB 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.
YR 2016
FD 2016-12-29
LK http://hdl.handle.net/10668/10730
UL http://hdl.handle.net/10668/10730
LA en
DS RISalud
RD Apr 6, 2025