Kroeze, StefanieKootstra, NeeltjeVan Nuenen, Ad C.Rossouw, Theresa M.Kityo, Cissy M.Siwale, MargaretAkanmu, SulaimonMandaliya, KishorDe Jager, MarleenOndoa, PascaleWit, Ferdinand W.Reiss, PeterRinke de Wit, Tobias F.Hamers, Raph L.2024-08-302024-08-302024-05Kroeze, S., Kootstra, N., Van Nuenen, A.C. et al. 2024, 'Specific plasma microRNAs are associated with CD4+ T-cell recovery during suppressive antiretroviral therapy for HIV-1', AIDS, vol. 38, pp. 791-801, doi : 10.1097/QAD.0000000000003853.0269-9370 (print)1473-5571 (online)10.1097/QAD.0000000000003853http://hdl.handle.net/2263/97965SUPPORTING INFORMATION: FILE S1: SUPPLEMENTAL DIGITAL CONTENTOBJECTIVE: 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.en© 2024 The Author(s).CD4þ T-cell recoveryHIV-1Immune dysregulationMicroRNAAntiretroviral therapy (ART)People with HIV (PWH)Human immunodeficiency virus (HIV)SDG-03: Good health and well-beingArticle