Lower Insulin Sensitivity Through 36 Months of Life With in Utero HIV and Antiretroviral Exposure in Botswana: Results From the Tshilo Dikotla Study.

Autor:	Jao J; Department of Pediatrics, Division of Pediatric Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Department of Pediatrics, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.; Botswana-Harvard Health Partnership, Gaborone, Botswana., Bonner LB; Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA., Dobinda K; Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA., Powis KM; Botswana-Harvard Health Partnership, Gaborone, Botswana.; Departments of Internal Medicine and Pediatrics, Massachusetts General Hospital, Boston, Massachusetts, USA.; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA., Sun S; Department of Pediatrics, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA., Legbedze J; Department of Pediatrics, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA., Mmasa KN; County Durham and Darlington NHS Foundation Trust, Darlington Co Durham, United Kingdom., Makhema J; Botswana-Harvard Health Partnership, Gaborone, Botswana., Mmalane M; Botswana-Harvard Health Partnership, Gaborone, Botswana., Kgole S; Botswana-Harvard Health Partnership, Gaborone, Botswana., Masasa G; Botswana-Harvard Health Partnership, Gaborone, Botswana., Moyo S; Botswana-Harvard Health Partnership, Gaborone, Botswana., Gerschenson M; Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii, USA., Mohammed T; Botswana-Harvard Health Partnership, Gaborone, Botswana., Abrams EJ; Mailman School of Public Health and Vagelos College of Physicians and Surgeons, ICAP at Columbia University, Columbia University, New York, New York, USA., Kurland IJ; Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA., Geffner ME; Keck School of Medicine of USC, The Saban Research Institute of Children's Hospital Los Angeles, Los Angeles, California, USA.
Jazyk:	angličtina
Zdroj:	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America [Clin Infect Dis] 2024 Sep 26; Vol. 79 (3), pp. 727-733.
DOI:	10.1093/cid/ciae088
Abstrakt:	Background: There are little data on changes in insulin sensitivity during the first few years of life following in utero human immunodeficiency virus (HIV) and antiretroviral (ARV) exposure. Methods: The Tshilo Dikotla study enrolled pregnant persons with HIV (PWH) (receiving tenofovir/emtricitabine or lamivudine plus dolutegravir or efavirenz) and pregnant individuals without HIV, as well as their liveborn children. Newborns were randomized to receive either zidovudine (AZT) or nevirapine (NVP) postnatal prophylaxis. Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) was assessed at birth and 1, 18, 24, and 36 months of life. We fit linear mixed-effects models to evaluate the association between in utero HIV/ARV exposure and average HOMA-IR from birth through 36 months of life, adjusting for confounders. Results: A total of 419 children were included (287 with in utero HIV/ARV exposure and uninfected [CHEU] and 132 without in utero HIV/ARV exposure [CHUU]). CHEU were born to older women (29.6 vs 25.3 years of age) with higher gravidity (3 vs 1). HOMA-IR was persistently higher in CHEU versus CHUU in adjusted analyses (mean difference of 0.07 in log10 HOMA-IR, P = .02) from birth through 36 months of life. Among CHEU, no differences in HOMA-IR were observed from birth through 36 months by in utero ARV exposure status or between AZT and NVP infant prophylaxis arms. Conclusions: In utero HIV/ARV exposure was associated with lower insulin sensitivity throughout the first 36 months of life, indicating persistent early life metabolic disturbances which may raise concern for poorer metabolic health later in life. Competing Interests: Potential conflicts of interest. M. E. G. has clinical trial contracts with Adrenas, Ascendis, Diurnal, Neurocrine Biosciences, Novo Nordisk, Pfizer, and Spruce Biosciences; is a consultant for Adrenas, Aeterna Zentaris, Ascendis, Eton Pharmaceuticals, Neurocrine Biosciences, Novo Nordisk, Pfizer, and Spruce Biosciences; and receives royalties from McGraw-Hill and UpToDate; payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing or educational events from Eton Pharmaceuticals. I. J. K. reports the following grants or contracts: NIH grant number P60DK020541. K. M. P. reports grants or contracts from NICHD and NIAID. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
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