{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T17:30:49Z","timestamp":1779903049936,"version":"3.53.1"},"reference-count":25,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T00:00:00Z","timestamp":1695772800000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Int AIDS Soc."],"published-print":{"date-parts":[[2023,9]]},"abstract":"Abstract<\/jats:title>Introduction<\/jats:title>Dolutegravir\u2010based antiretroviral therapy (ART) is the preferred antiretroviral treatment for children and adolescents living with HIV. A large surveillance study in Botswana previously raised concerns about an association between pre\u2010conception dolutegravir and neural tube defects. Before these concerns were subsequently resolved, we set up a sub\u2010study to look at the effect of dolutegravir on levels of folate and vitamin B12 in children and adolescents within the randomized ODYSSEY trial, as folate and vitamin B12 are known to play a crucial role in neural tube development.<\/jats:p><\/jats:sec>Methods<\/jats:title>We conducted the sub\u2010study among Ugandan ODYSSEY participants and compared folate and vitamin B12 between children randomized to dolutegravir\u2010based ART (DTG) and non\u2010dolutegravir\u2010based standard\u2010of\u2010care treatment (SOC). Plasma folate was measured at enrolment and week 4 on stored samples; in addition, plasma and red blood cell (RBC) folate and vitamin B12 were assayed at week \u226596 in prospectively collected samples. RBC mean corpuscular volume (MCV) was measured 24\u2010weekly in all ODYSSEY participants. Samples analysed in the sub\u2010study were collected between September 2016 and October 2020.<\/jats:p><\/jats:sec>Results<\/jats:title>A total of 229 children aged \u22656 years were included in the sub\u2010study with median age at trial enrolment of 12.3 (interquartile range [IQR] 9.0, 14.7) years, and CD4 count of 501 (IQR 228, 695); 112 (49%) children were male. Most participants (225\/229, 98%) had plasma folate results at enrolment and 214 (93%) children had results available for RBC folate, vitamin B12 and plasma folate at week \u226596. MCV results were analysed on 679 children aged \u22656 years enrolled in ODYSSEY. At week 4, mean plasma folate was significantly higher in the dolutegravir arm than in SOC (difference [DTG\u2010SOC] 1.6 ng\/ml, 95% CI 0.8, 2.3; p<\/jats:italic><0.001), and this difference persisted to week \u226596 (2.7 ng\/ml, 95% CI 1.7, 3.7; p<\/jats:italic><0.001). Mean RBC folate at \u226596 weeks was also higher in the DTG arm (difference 73 ng\/ml, 95% CI 3, 143; p<\/jats:italic> = 0.041). There was no difference in the treatment arms for vitamin B12 levels at \u226596 weeks or change in MCV through trial follow\u2010up.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Plasma and RBC folate levels were higher in children and adolescents receiving dolutegravir\u2010based ART than on other ART regimens. Further studies are needed to clarify the mechanisms of these interactions and the clinical implications of increased blood folate levels.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jia2.26174","type":"journal-article","created":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T06:09:04Z","timestamp":1695881344000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effect of dolutegravir on folate, vitamin B12 and mean corpuscular volume levels among children and adolescents with HIV: a sub\u2010study of the ODYSSEY randomized controlled trial"],"prefix":"10.1002","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3241-2141","authenticated-orcid":false,"given":"Linda Namutebi","family":"Barlow\u2010Mosha","sequence":"first","affiliation":[{"name":"Makerere University\u2010Johns Hopkins University (MU\u2010JHU) Research Collaboration Kampala 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