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

• Published in: Clinical microbiology and infection Vol. 23; no. 5; pp. 318 - 324
• Main 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.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2017
• Subjects: Acquired Immunodeficiency Syndrome - diagnosis; Adolescent; Adolescents; CCR5(WT/Δ32); CD4-Positive T-Lymphocytes - virology; Child; Child, Preschool; DNA, Viral - isolation & purification; Female; Genotyping Techniques; HIV Infections - diagnosis; HIV-1; Human immunodeficiency virus-1; Humans; Male; Pregnancy; Receptors, CCR5 - genetics; Reservoir size; Retrospective Studies; Viral Load; Young Adult; Young adults; Young adults; Adolescents; CCR5(WT/Δ32); Reservoir size; Human immunodeficiency virus-1; CCR5((WT/Δ32))
• ISSN: 1198-743X; 1469-0691
• DOI: 10.1016/j.cmi.2016.12.020

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.