Sahera Dirajlal-Fargo1,2,3, Jiao Yu3, Zainab Albar3, Abdus Sattar3, Sana Mahtab4, Jennifer Jao5, Landon Myer6, Heather J Zar4, Grace A McComsey1,2,3. 1. University Hospitals Cleveland Medical Center. 2. Rainbow Babies and Children's Hospital. 3. Case Western Reserve University, Cleveland, Ohio, USA. 4. Red Cross War Memorial Children's Hospital and MRC Unit on Child & Adolescent Health, University of Cape Town, Cape Town, South Africa. 5. Northwestern Feinberg School of Medicine, Chicago, Illinois, USA. 6. Division of Epidemiology & Biostatistics, School of Public Health & Family Medicine, University of Cape Town, Cape Town, South Africa.
Abstract
BACKGROUND: There is evidence for endothelial dysfunction in youth living with perinatally acquired HIV (YLPHIV). However, little data exist on its mechanisms. METHODS: YLPHIV and age-matched HIV-uninfected (HIV-) youth enrolled in the Cape Town Adolescent Antiretroviral Cohort in South Africa between 9 and 14 years of age were included. YLPHIV were on antiretroviral therapy more than 6 months with viral load less than 400 copies/ml at baseline and 24 months. Serum biomarkers of systemic inflammation, monocyte activation, intestinal integrity, and oxidized LDL-cholesterol were measured at baseline and after 24 months. Endothelial function was measured at 24 months using reactive hyperemic index (RHI); endothelial dysfunction was defined as RHI less than 1.35. Spearman correlation coefficient and quantile regression were used to examine associations between RHI and different biomarkers. RESULTS: We included 266 YLPHIV and 69 HIV- participants. At baseline, median (Q1, Q3) age was 12 (11, 13) years and 53% were females. YLPHIV had poorer endothelial function compared with HIV- youth (RHI = 1.36 vs. 1.52, P < 0.01). At baseline and 24 months, YLPHIV had higher markers of monocyte activation (soluble CD14), gut barrier dysfunction (intestinal fatty acid binding protein) and oxidized LDL-cholesterol (P ≤ 0.04) compared with HIV- youth. Among YLPHIV, soluble CD14 remained associated with endothelial dysfunction after adjusting for age, sex, Tanner stage, and antiretroviral therapy duration (β: -0.05, P = 0.01). CONCLUSION: Despite viral suppression, South African YLPHIV have poor endothelial function and persistent evidence of monocyte activation and gut barrier dysfunction compared with HIV- youth. The long-term clinical significance of gut integrity and monocyte activation needs to be further assessed in YLPHIV.
BACKGROUND: There is evidence for endothelial dysfunction in youth living with perinatally acquired HIV (YLPHIV). However, little data exist on its mechanisms. METHODS: YLPHIV and age-matched HIV-uninfected (HIV-) youth enrolled in the Cape Town Adolescent Antiretroviral Cohort in South Africa between 9 and 14 years of age were included. YLPHIV were on antiretroviral therapy more than 6 months with viral load less than 400 copies/ml at baseline and 24 months. Serum biomarkers of systemic inflammation, monocyte activation, intestinal integrity, and oxidized LDL-cholesterol were measured at baseline and after 24 months. Endothelial function was measured at 24 months using reactive hyperemic index (RHI); endothelial dysfunction was defined as RHI less than 1.35. Spearman correlation coefficient and quantile regression were used to examine associations between RHI and different biomarkers. RESULTS: We included 266 YLPHIV and 69 HIV- participants. At baseline, median (Q1, Q3) age was 12 (11, 13) years and 53% were females. YLPHIV had poorer endothelial function compared with HIV- youth (RHI = 1.36 vs. 1.52, P < 0.01). At baseline and 24 months, YLPHIV had higher markers of monocyte activation (soluble CD14), gut barrier dysfunction (intestinal fatty acid binding protein) and oxidized LDL-cholesterol (P ≤ 0.04) compared with HIV- youth. Among YLPHIV, soluble CD14 remained associated with endothelial dysfunction after adjusting for age, sex, Tanner stage, and antiretroviral therapy duration (β: -0.05, P = 0.01). CONCLUSION: Despite viral suppression, South African YLPHIV have poor endothelial function and persistent evidence of monocyte activation and gut barrier dysfunction compared with HIV- youth. The long-term clinical significance of gut integrity and monocyte activation needs to be further assessed in YLPHIV.
Authors: Theodoros Kelesidis; Thuy Tien T Tran; James H Stein; Todd T Brown; Carlee Moser; Heather J Ribaudo; Michael P Dube; Robert Murphy; Otto O Yang; Judith S Currier; Grace A McComsey Journal: Clin Infect Dis Date: 2015-04-22 Impact factor: 9.079
Authors: Netanya G Sandler; Handan Wand; Annelys Roque; Matthew Law; Martha C Nason; Daniel E Nixon; Court Pedersen; Kiat Ruxrungtham; Sharon R Lewin; Sean Emery; James D Neaton; Jason M Brenchley; Steven G Deeks; Irini Sereti; Daniel C Douek Journal: J Infect Dis Date: 2011-01-20 Impact factor: 5.226
Authors: Corrilynn O Hileman; Randi Turner; Nicholas T Funderburg; Richard D Semba; Grace A McComsey Journal: AIDS Date: 2016-01-02 Impact factor: 4.177
Authors: Lewis H Kuller; Russell Tracy; Waldo Belloso; Stephane De Wit; Fraser Drummond; H Clifford Lane; Bruno Ledergerber; Jens Lundgren; Jacqueline Neuhaus; Daniel Nixon; Nicholas I Paton; James D Neaton Journal: PLoS Med Date: 2008-10-21 Impact factor: 11.069
Authors: Adelzon A Paula; Mauro Schechter; Suely H Tuboi; José Claudio Faulhaber; Paula M Luz; Valdiléa G Veloso; Ronaldo I Moreira; Beatriz Grinsztejn; Lee H Harrison; Antonio G Pacheco Journal: PLoS One Date: 2014-04-11 Impact factor: 3.240
Authors: Adriana Weinberg; Mark J Giganti; Patricia A Sirois; Grace Montepiedra; Jennifer Canniff; Allison Agwu; Michael J Boivin; Suad Kapetanovic; Mark J Abzug Journal: AIDS Date: 2022-04-19 Impact factor: 4.632