Specific plasma microRNAs are associated with CD4+ T-cell recovery during suppressive antiretroviral therapy for HIV-1.
Kroeze S., Kootstra NA., van Nuenen AC., Rossouw TM., Kityo CM., Siwale M., Akanmu S., Mandaliya K., de Jager M., Ondoa P., Wit FW., Reiss P., Rinke de Wit TF., Hamers RL.
ObjectiveThis study investigated the association of plasma microRNAs before and during antiretroviral therapy (ART) with poor CD4+ T-cell recovery during the first year of ART.DesignMicroRNAs 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.MethodsFirst, the levels of 179 microRNAs were screened in a subset of participants from the lowest and highest tertiles of CD4+ T-cell recovery (ΔCD4) (N = 12 each). Next, 11 discordant microRNAs, were validated in 113 participants (lowest tertile ΔCD4: n = 61, highest tertile ΔCD4: n = 52). For discordant microRNAs in the validation, a pathway analysis was conducted. Lastly, we compared microRNA levels of PWH to HIV-negative controls.ResultsPoor CD4+ T-cell recovery was associated with higher levels of hsa-miR-199a-3p 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 hsa-miR-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 CD4+ T-cell recovery only.ConclusionThese findings add to the understanding of pathways involved in persistent HIV-induced immune dysregulation during suppressive ART.