How Does ART Affect Children’s Immune Responses?

Antiretroviral therapy (ART) may have an impact on the way immune responses against HIV, cytomegalovirus (CMV), and tuberculosis (TB) are reconstituted in children with HIV in terms of alterations in T-cell phenotype, function, and programmed cell death 1 (PD-1) expression, according to a new study. 

To analyze ART’s impact on the HIV-, CMV-, and TB-specific T-cell responses in children, the researchers used intracellular cytokine (interleukin-2, interferon-γ, tumor necrosis factor-α) staining assays after in-vitro stimulation. The responses before ART and 1 year after ART initiation were compared.

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The researchers also measured the expression of activation, immune exhaustion, and memory phenotype markers and studied proliferative responses after antigen stimulation, as well. In all, the data on 25 children from a clinic in South Africa with HIV were evaluated.

The pathogens each had a distinct pattern of immune reconstitution after 1 year of ART. These differential, pathogen-specific changes were seen in cytokine profiles of CD4 T-cell responses that were associated with shifts in memory phenotype and decreased PD-1 expression.

After 1 year of ART, there were also increases in proliferative capacity of HIV- and purified peptide derivative-specific responses. The researchers also determined there to be a link between the recovery of CMV- and TB-specific responses and a decrease in PD-1 expression.

“Immune checkpoint inhibitors that target the PD-1 pathway may represent a potential intervention in patients with insufficient immune reconstitution on ART,” the researchers concluded.

—Colleen Murphy

Reference:

Muenchhoff M, Adland E, Roider J, et al. Differential pathogen-specific immune reconstitution in antiretroviral therapy-treated human immunodeficiency virus-infected children. J Infect Dis. 2019;219(9):1407-1417. https://doi.org/10.1093/infdis/jiy668.