Immune correlates of HIV-1 reservoir cell decline in early-treated infants

Initiation of antiretroviral therapy (ART) in infected neonates within hours after birth limits viral reservoir seed-ing but does not prevent long-term HIV-1 persistence. Here, we report parallel assessments of HIV-1 reservoir cells and innate antiviral immune responses in a unique cohort of 37 infected neonates from Botswana who started ART extremely early, frequently within hours after birth. Decline of genome-intact HIV-1 proviruses occurs rapidly after initiation of ART and is associated with an increase in natural killer (NK) cell populations expressing the cytotoxicity marker CD57 and with a decrease in NK cell subsets expressing the inhibitory marker NKG2A. Immune perturbations in innate lymphoid cells, myeloid dendritic cells, and monocytes de-tected at birth normalize after rapid institution of antiretroviral therapy but do not notably influence HIV-1 reservoir cell dynamics. These results suggest that HIV-1 reservoir cell seeding and evolution in early-treated neonates is markedly influenced by antiviral NK cell immune responses.

Automated summary

Initiation of early antiretroviral therapy in infected neonates can limit viral reservoir seeding, but it does not prevent long-term HIV-1 persistence. The study found that rapid decline of HIV-1 proviruses occurred after initiation of ART in neonates, accompanied by an increase in cytotoxic natural killer (NK) cell populations and a decrease in inhibitory NK cell subsets. Immune perturbations observed in certain immune cell types at birth were normalized after early institution of antiretroviral therapy, but they did not significantly influence HIV-1 reservoir cell dynamics.