Early cART Initiation Benefits Children Infected With HIV-1 Perinatally

Initiating combination antiretroviral therapy (cART) early in infancy resulted in lower blood HIV reservoir, an effect that was observed until adolescence, according to study results published in Clinical Infectious Diseases. The low reservoir was independently associated with treatment precocity, protective human leukocyte antigen, and low cumulative viremia.

In this prospective study, researchers aimed to determine the influence of age at cART initiation by comparing HIV reservoirs in children infected by mother-to-child transmission in a younger group (aged 5 to 12 years) and adolescents (aged 13 to 17 years) who began cART before the age of 6 months (early group) vs after 2 years of age (late group).

The study enrolled 76 participants who attained HIV RNA lower than 400 copies/mL less than 24 months after cART initiation, irrespective of subsequent viral suppression. The early group included 27 children and 9 adolescents; the late group included 19 children and 21 adolescents. Blood samples were collected over a period of 2 years.

All participants were on antiretroviral therapy (ART); 83% were virologically suppressed and 92% had a CD4+ T cell count greater than 500 cells/µL. The median total HIV DNA levels were lower in the early-treated participants than in the late-treated participants (2.17 vs 2.95 log copies/million peripheral blood mononuclear cells [PBMCs], respectively; P <.0001).

Moreover, the median total HIV DNA level was lower in the early-treated group in both age groups: 2.14 vs 2.87 log copies/million PBMCs in children (P <.0001) and 2.25 vs 2.98 log copies/million PBMCs in adolescents (P =.019).

To determine the parameters independently associated with the total HIV DNA level, researchers performed 2 different multivariate analyses: a full model on the entire population, including the normalized cumulative viremia since cART, and a restricted analysis of 63 patients with current HIV RNA less than 50 copies/mL.

In the full model, early cART and cumulative viremia were independently associated with lower HIV DNA levels (P <.0001 and P =.0024, respectively). In the restricted analysis, early cART, cumulative viremia, and protective human leukocyte antigen alleles were independently associated with lower HIV DNA levels.

Researchers noted that in participants with sustained virological control, HIV DNA levels were significantly lower in naive CD4+ T cells (median, 2.65 copies/million cells) than in each of the 3 memory CD4+ T cells: 3.57 copies/million cells for central memory CD4+ T cells (P =.031); 3.87 copies/million cells for transitional memory CD4+ T cells (P =.028); and 3.66 copies/million cells for effector memory CD4+ T cells (P =.008). In addition, transitional memory and effector memory CD4+T cells were less infected in the early group than in the late group: 3.44 vs 4.03 copies/million cells (P =.03) and 3.22 vs 3.96 copies/million cells (P =.02), respectively.

In a substudy of 9 participants (4 in the early group, 5 in the late group; 1 child, 8 adolescents), despite early cART and low HIV reservoir, PBMCs were able to produce HIV RNA after ex vivo activation.

Future larger studies will need to confirm this finding because participants treated from the time of infection did not show reduced viral inducibility compared with those treated later.

Reference

Avettand-Fenoel V, Lechenadec J, Diallo MS, et al; for the ANRS-EP59-CLEAC Study Group. Initiating antiretroviral treatment early in infancy has long-term benefits on the HIV reservoir in late childhood and adolescence. Clin Infect Dis. Published online January 4, 2021. doi:10.1093/cid/ciaa1931