The size of HIV reservoir is associated with telomere shortening and immunosenescence in early ART-treated HIV-infected children

Authors: De Rossi A, Dalzini A, Ballin G, Dominguez-Rodriuguez S, Rojo P, Foster C, Palma P, Sessa L, Nastouli E, Pahwa S, Rossi P, Giaquinto C, AEPIICAL Consortium

2020/07/13

Oral presentation at 23rd Virtual International AIDS Conference, July 2020

Background: HIV infection is linked to premature senescence, with increased risk of aging-associated illnesses. Early ART has been associated with a reduced HIV reservoir in HIV-perinatally infected children (PHIV), but its impact on the senescence process is an open question. Telomeres are critical for cellular replicative potential and their shortening is a marker of cellular senescence and aging process. We investigated the relationship between immunosenescence and HIV reservoir in PHIV enrolled in a multicenter cross-sectional study (CARMA, EPIICAL consortium).

Methods: 37 PHIV, who started ART <2 years of age and had undetectable viremia for at least 5 years, were enrolled in this study. HIV-DNA copies on CD4 cells and relative telomere length and levels of T-cell receptor rearrangement excision circle (TREC, marker of thymic output) on CD4 and CD8 cells were quantified by qPCR. Senescent and activated CD4 and CD8 cells were estimated by flow cytometry. To explore the associations between cellular parameters, HIV reservoir and age at ART initiation, data were analyzed using a multivariable Poisson regression (adjusted for baseline % CD4, plasmaviremia, age at reservoir measurement, and age at ART initiation as interaction term).

Results: HIV reservoir was significantly (p<0.001) associated with immunosenescence (1.23[1.21-1.26]) and telomere shortening (0.15[0.13-0.17]) in CD4 cells, and immune activation (3.67[3.49-3.85]) and TREC levels (1.08[1.06-1.11]) in CD8 cells. These associations decreased by 1%, 10%, 6% and 6%, respectively, for each month ART was delayed. Early treated PHIV (ART initiation ≤6 months of age) displayed significantly lower HIV-DNA level (89[56-365] vs 552[303-1001] copies/106 cells)  and % CD4 senescent cells (1.0[0.5-2.7] vs 2.9[2.0-6.3]) than late treated ones.