Background: Early combined antiretroviral therapy (cART) initiation reduces progression to AIDS and death and decreases the cell-associated viral reservoir in children infected with HIV-1 during the perinatal period. Little data are available on the benefit of early cART initiation for children over five years of age and adolescents. The ANRS-EP59-CLEAC study aimed to assess the immunological and virological characteristics of HIV-1-infected children and adolescents who achieved initial virological suppression, according to age at cART initiation (< 6 months vs. ≥ 24 months of age).
Methods: Patient recruitment was conducted in the Paris area between 2016 and 2018. Total cell-associated HIV-1 DNA was quantified in the blood using ultrasensitive real-time PCR (adapted from Biocentric, Bandol, France). CD4 and CD8 CD45RA+CCR7+ naive T lymphocytes were quantified in fresh blood by flow cytometry. The Kruskal-Wallis test was used to compare the parameters of early/late treated children (5-12 years) and adolescents (13-17 years).
Results: We prospectively enrolled 27 children (E-Ch) and nine adolescents (E-Ado) in the early-cART group, and 19 children (L-Ch) and 21 adolescents (L-Ado) in the late-cART group. The patients were mainly girls (54%), born in mainland France (60%) to mothers originating from Sub-Saharan African countries (74%). At the time of the study, all patients were receiving ART, 76% had undetectable plasma HIV-1 RNA, and the median (interquartile range) CD4 T-cell count was 824 [660; 1167] cells/µl. HIV-1 DNA levels were lower in the early-cART than late-cART groups for both children and adolescents (medians were 2.2 (E-Ch), 2.9 (L-Ch), 2.3 (E-Ado), and 3.0 (L-Ado) log₁₀ copies/10⁶ PBMCs, P < 0.0001). Data on the percentage of naive CD4 and CD8 T lymphocytes were available for 58 subjects. We observed the highest percentages in E-Ch (medians in the E-Ch, L-Ch, E-Ado, and L-Ado groups were respectively 61, 54, 36, and 55% for CD4, P = 0.02; and 50, 33, 29, and 29%, for CD8, P = 0.004).
Conclusions: Early cART initiation during infancy is associated with lower short- and long-term PBMC-associated HIV-1 DNA levels, as targeted in HIV-1 remission strategies. An immunological benefit of early cART initiation on naive T lymphocytes was suggested in children from this study.