Abstract
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.
Original language | English (US) |
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Pages (from-to) | 727-733 |
Number of pages | 7 |
Journal | Clinical Infectious Diseases |
Volume | 79 |
Issue number | 3 |
DOIs | |
State | Published - Sep 15 2024 |
Funding
This study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH) through grant number R01DK109881. M, G. was also funded by the National Institute of General Medicine Sciences, NIH grant number P20GM113134. I. J. K. reports support for this work from NIDDK for ES-DRC. M. E. G. receives consultant fees from Gilead Sciences, Inc. I. J. K. was supported by the Stable Isotope and Metabolomics Core Facility of the Diabetes Research and Training Center (DRTC) of the Albert Einstein College of Medicine (NIH grant number P60DK020541). 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. Financial support. This study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH) through grant number R01DK109881. M, G. was also funded by the National Institute of General Medicine Sciences, NIH grant number P20GM113134. I. J. K. reports support for this work from NIDDK for ES-DRC. M. E. G. receives consultant fees from Gilead Sciences, Inc. I. J. K. was supported by the Stable Isotope and Metabolomics Core Facility of the Diabetes Research and Training Center (DRTC) of the Albert Einstein College of Medicine (NIH grant number P60DK020541). 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\u2019s 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.
Keywords
- homeostatic model assessment
- in utero HIV exposure
- insulin sensitivity
- metabolic
- perinatal HIV exposure
ASJC Scopus subject areas
- Microbiology (medical)
- Infectious Diseases