Abstract:
OBJECTIVE: This study investigated the association of plasma microRNAs before and during
antiretroviral therapy (ART) with poor CD4þ T-cell recovery during the first year of ART.
DESIGN: MicroRNAs were retrospectively measured in stored plasma samples from people
with HIV (PWH) in sub-Saharan Africa who were enrolled in a longitudinal multicountry
cohort and who had plasma viral-load less than 50 copies/ml after 12 months of ART.
METHODS: First, the levels of 179 microRNAs were screened in a subset of participants
from the lowest and highest tertiles of CD4þ T-cell recovery (DCD4) (N ¼ 12 each).
Next, 11 discordant microRNAs, were validated in 113 participants (lowest tertile
DCD4: n ¼ 61, highest tertile DCD4: n ¼ 52). For discordant microRNAs in the validation, a pathway analysis was conducted. Lastly, we compared microRNA levels of PWH
to HIV-negative controls.
RESULTS: Poor CD4þ T-cell recovery was associated with higher levels of hsa-miR-199a3p and hsa-miR-200c-3p before ART, and of hsa-miR-17-5p and hsa-miR-501-3p
during ART. Signaling by VEGF and MET, and RNA polymerase II transcription pathways were identified as possible targets of hsa-miR-199a-3p, hsa-200c-3p, and hsamiR-17-5p. Compared with HIV-negative controls, we observed lower hsa-miR-326,
hsa-miR-497-5p, and hsa-miR-501-3p levels before and during ART in all PWH, and
higher hsa-miR-199a-3p and hsa-miR-200c-3p levels before ART in all PWH, and
during ART in PWH with poor CD4þ T-cell recovery only.
CONCLUSION: These findings add to the understanding of pathways involved in persistent
HIV-induced immune dysregulation during suppressive ART.
