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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.

Original publication

DOI

10.1097/qad.0000000000003853

Type

Journal

AIDS (London, England)

Publication Date

02/2024

Addresses

Amsterdam Institute for Global Health and Development.