Specific plasma microRNAs are associated with CD4+ T-cell recovery during suppressive antiretroviral therapy for HIV-1

dc.contributor.authorKroeze, Stefanie
dc.contributor.authorKootstra, Neeltje
dc.contributor.authorVan Nuenen, Ad C.
dc.contributor.authorRossouw, Theresa M.
dc.contributor.authorKityo, Cissy M.
dc.contributor.authorSiwale, Margaret
dc.contributor.authorAkanmu, Sulaimon
dc.contributor.authorMandaliya, Kishor
dc.contributor.authorDe Jager, Marleen
dc.contributor.authorOndoa, Pascale
dc.contributor.authorWit, Ferdinand W.
dc.contributor.authorReiss, Peter
dc.contributor.authorRinke de Wit, Tobias F.
dc.contributor.authorHamers, Raph L.
dc.date.accessioned2024-08-30T13:14:08Z
dc.date.available2024-08-30T13:14:08Z
dc.date.issued2024-05
dc.descriptionSUPPORTING INFORMATION: FILE S1: SUPPLEMENTAL DIGITAL CONTENTen_US
dc.description.abstractOBJECTIVE: 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_US
dc.description.departmentImmunologyen_US
dc.description.sdgSDG-03:Good heatlh and well-beingen_US
dc.description.sponsorshipA Veni postdoc fellowship to R.L.H. through the Dutch Research Council (NWO) Talent Programme (91615036), and Gilead Sciences Netherlands through an unrestricted scientific grant.en_US
dc.description.urihttps://journals.lww.com/aidsonline/pages/default.aspxen_US
dc.identifier.citationKroeze, 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.en_US
dc.identifier.issn0269-9370 (print)
dc.identifier.issn1473-5571 (online)
dc.identifier.other10.1097/QAD.0000000000003853
dc.identifier.urihttp://hdl.handle.net/2263/97965
dc.language.isoenen_US
dc.publisherLippincott, Williams & Wilkinsen_US
dc.rights© 2024 The Author(s).en_US
dc.subjectCD4þ T-cell recoveryen_US
dc.subjectHIV-1en_US
dc.subjectImmune dysregulationen_US
dc.subjectMicroRNAen_US
dc.subjectAntiretroviral therapy (ART)en_US
dc.subjectPeople with HIV (PWH)en_US
dc.subjectHuman immunodeficiency virus (HIV)en_US
dc.subjectSDG-03: Good health and well-beingen_US
dc.titleSpecific plasma microRNAs are associated with CD4+ T-cell recovery during suppressive antiretroviral therapy for HIV-1en_US
dc.typeArticleen_US

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