Effect of dolutegravir on folate, vitamin B12 and mean corpuscular volume levels among children and adolescents with HIV: a sub-study of the ODYSSEY randomized controlled trial.

Autor: Barlow-Mosha LN; Makerere University-Johns Hopkins University (MU-JHU) Research Collaboration, Kampala, Uganda., Ahimbisibwe GM; Makerere University-Johns Hopkins University (MU-JHU) Research Collaboration, Kampala, Uganda., Chappell E; MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, UK., Amuge PM; Baylor College of Medicine Children's Foundation-Uganda, Kampala, Uganda., Nanduudu A; Joint Clinical Research Centre, Kampala, Uganda., Kaudha E; Joint Clinical Research Centre, Kampala, Uganda., Amukele T; Department of Pathology, ICON Central Laboratories Inc, Farmingdale, New York, USA., Balamusani D; Infectious Diseases Institute Core Laboratory, Kampala, Uganda., Kafufu B; Infectious Diseases Institute Core Laboratory, Kampala, Uganda., Nimwesiga A; Infectious Diseases Institute Core Laboratory, Kampala, Uganda., Kataike H; Makerere University-Johns Hopkins University (MU-JHU) Research Collaboration, Kampala, Uganda., Namwanje R; Makerere University-Johns Hopkins University (MU-JHU) Research Collaboration, Kampala, Uganda., Kasangaki G; Makerere University-Johns Hopkins University (MU-JHU) Research Collaboration, Kampala, Uganda., Mulindwa A; Joint Clinical Research Centre, Kampala, Uganda., Muzorah GA; Baylor College of Medicine Children's Foundation-Uganda, Kampala, Uganda., Bbuye D; Baylor College of Medicine Children's Foundation-Uganda, Kampala, Uganda., Musiime V; Joint Clinical Research Centre, Kampala, Uganda.; Department of Paediatrics and Child Health, Makerere University College of Health Sciences, Kampala, Uganda., Mujyambere E; Joint Clinical Research Centre, Kampala, Uganda., Ssenyonga M; Makerere University-Johns Hopkins University (MU-JHU) Research Collaboration, Kampala, Uganda., Mulima D; Joint Clinical Research Centre, Kampala, Uganda., Kyambadde RC; Makerere University-Johns Hopkins University (MU-JHU) Research Collaboration, Kampala, Uganda., Namusanje J; Joint Clinical Research Centre, Kampala, Uganda., Isabirye R; Makerere University-Johns Hopkins University (MU-JHU) Research Collaboration, Kampala, Uganda., Nabalamba M; Joint Clinical Research Centre, Kampala, Uganda., Nakirya BM; Makerere University-Johns Hopkins University (MU-JHU) Research Collaboration, Kampala, Uganda., Kityo C; Joint Clinical Research Centre, Kampala, Uganda., Kekitiinwa AR; Baylor College of Medicine Children's Foundation-Uganda, Kampala, Uganda., Giaquinto C; Department of Women and Child Health, University of Padova, Padova, Italy., Copp A; UCL Great Ormond Street Institute of Child Health, London, UK., Gibb DM; MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, UK., Ford D; MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, UK., Musoke P; Makerere University-Johns Hopkins University (MU-JHU) Research Collaboration, Kampala, Uganda.; Department of Paediatrics and Child Health, Makerere University College of Health Sciences, Kampala, Uganda., Turkova A; MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, UK.
Jazyk: angličtina
Zdroj: Journal of the International AIDS Society [J Int AIDS Soc] 2023 Sep; Vol. 26 (9), pp. e26174.
DOI: 10.1002/jia2.26174
Abstrakt: Introduction: Dolutegravir-based 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-conception dolutegravir and neural tube defects. Before these concerns were subsequently resolved, we set up a sub-study 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.
Methods: We conducted the sub-study among Ugandan ODYSSEY participants and compared folate and vitamin B12 between children randomized to dolutegravir-based ART (DTG) and non-dolutegravir-based standard-of-care 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 ≥96 in prospectively collected samples. RBC mean corpuscular volume (MCV) was measured 24-weekly in all ODYSSEY participants. Samples analysed in the sub-study were collected between September 2016 and October 2020.
Results: A total of 229 children aged ≥6 years were included in the sub-study 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 ≥96. MCV results were analysed on 679 children aged ≥6 years enrolled in ODYSSEY. At week 4, mean plasma folate was significantly higher in the dolutegravir arm than in SOC (difference [DTG-SOC] 1.6 ng/ml, 95% CI 0.8, 2.3; p<0.001), and this difference persisted to week ≥96 (2.7 ng/ml, 95% CI 1.7, 3.7; p<0.001). Mean RBC folate at ≥96 weeks was also higher in the DTG arm (difference 73 ng/ml, 95% CI 3, 143; p = 0.041). There was no difference in the treatment arms for vitamin B12 levels at ≥96 weeks or change in MCV through trial follow-up.
Conclusions: Plasma and RBC folate levels were higher in children and adolescents receiving dolutegravir-based 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.
(© 2023 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje