Gut permeability is associated with lower insulin sensitivity in youth with perinatally acquired HIV
Year: 2024
Type: article
Abstract: The relationships between alterations in the intestinal barrier, and bacterial translocation with the development of metabolic complications in youth with perinatally acquired HIV (YPHIV) have not been investigated. The PHACS Adolescent Master Protocol enrolled YPHIV across 15 U.S. sites, including Puerto Rico, from 2007 to 2009. For this analysis, we included YPHIV with HIV viral load 1000 c/ml or less, with at least one measurement of homeostatic assessment of insulin resistance (HOMA-IR) or nonhigh density lipoprotein (non-HDLc) between baseline and year 3 and plasma levels of intestinal fatty-acid binding protein (I-FABP), lipopolysaccharide-binding protein (LBP), and zonulin levels at baseline. We fit linear regression models using generalized estimating equations to assess the association of baseline log 10 gut markers with log 10 HOMA-IR and non-HDLc at all timepoints. HOMA-IR or non-HDLc was measured in 237, 189, and 170 PHIV at baseline, Yr2, and Yr3, respectively. At baseline, median age (Q1, Q3) was 12 years (10, 14), CD4 + cell count was 762 cells/μl (574, 984); 90% had HIV RNA less than 400 c/ml. For every 10-fold higher baseline I-FABP, HOMA-IR dropped 0.85-fold at baseline and Yr2. For a 10-fold higher baseline zonulin, there was a 1.35-fold increase in HOMA-IR at baseline, 1.23-fold increase in HOMA-IR at Yr2, and 1.20-fold increase in HOMA-IR at Yr3 in adjusted models. For a 10-fold higher baseline LBP, there was a 1.23-fold increase in HOMA-IR at baseline in the unadjusted model, but this was slightly attenuated in the adjusted model. Zonulin was associated with non-HDLc at baseline, but not for the other time points. Despite viral suppression, intestinal damage may influence downstream insulin sensitivity in YPHIV.
Source: AIDS
Authors: Sahera Dirajlal-Fargo, Wendy Yu, Denise L. Jacobson, Ayesha Mirza, Mitchell E. Geffner, Jennifer Jao, Grace A. McComsey, for the Pediatric HIV/AIDS Cohort Study (PHACS)
Language: English
Subfield: Emergency Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: U.S. Department of Health and Human Services, Pfizer, Gilead Sciences, University of Miami, Tulane University, Harvard T.H. Chan School of Public Health, Astellas Pharma, National Institutes of Health, Genentech, University of California, San Diego, University of Colorado Denver, National Institute on Alcohol Abuse and Alcoholism, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Cancer Institute, National Institute on Deafness and Other Communication Disorders, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Dental and Craniofacial Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1121950248, Pediatric HIV/AIDS Cohort Study (PHACS) 2020, G1526836824, G3215336396, G4605344243, Pediatric HIV/AIDS Cohort Study (PHACS) Coordinating Center (CC) (U01), Pediatric HIV/AIDS Cohort Study (PHACS): Data and Operations Center (DOC)., G8073633191, G8582443069, Clinical and Translational Science Collaborative of Northern Ohio, Catalyzing Linkages for Everyone's Health (CLE Health), The Cleveland Digestive Diseases Research Core Center (DDRCC)
OpenAlex ID: W4393563368
