Sara E Looby1,2, Amy Kantor3, Tricia H Burdo4, Judith S Currier5, Carl J Fichtenbaum6, Edgar T Overton7, Judith A Aberg8, Carlos D Malvestutto9, Gerald S Bloomfield10, Kristine M Erlandson11, Michelle Cespedes8, Esper G Kallas12, Mar Masiá13, Alice C Thornton14, Mandy D Smith4, Jacqueline M Flynn4, Emma M Kileel1, Evelynne Fulda1, Kathleen V Fitch1, Michael T Lu15, Pamela S Douglas16, Steven K Grinspoon1, Heather J Ribaudo3, Markella V Zanni1. 1. Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. 2. Yvonne L. Munn Center for Nursing Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. 3. Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA. 4. Department of Microbiology, Immunology, and Inflammation and Center for NeuroVirology and Gene Editing, Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania, USA. 5. Division of Infectious Diseases, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California, USA. 6. Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. 7. Division of Infectious Diseases, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, USA. 8. Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA. 9. Division of Infectious Diseases, Ohio State University Medical Center, Columbus, Ohio, USA. 10. Department of Medicine, Duke Global Health Institute and Duke Clinical Research Institute, Duke University, Durham, North Carolina, USA. 11. Department of Medicine, Division of Infectious Disease, University of Colorado-nschutz Medical Campus, Aurora, Colorado, USA. 12. Departmento de Molestias Infecciosas e Parasitárias, University of Sao Paulo, Sao Paulo, Brazil. 13. Department of Infectious Diseases, Hospital General Universitario de Elche, Alicante, CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Spain. 14. Division of Infectious Diseases, University of Kentucky College of Medicine, Lexington, Kentucky, USA. 15. Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. 16. Duke University Research Institute, Duke University School of Medicine, Durham North Carolina, USA.
Abstract
BACKGROUND: Among antiretroviral therapy (ART)-treated people with human immunodeficiency virus (PWH), persistent systemic immune activation contributes to atherogenesis atherosclerotic, cardiovascular disease (CVD) events, and mortality. Factors associated with key immune activation indices have not previously been characterized among a global primary CVD prevention cohort of PWH. METHODS: Leveraging baseline Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) data, we evaluated factors associated with soluble CD14 (sCD14) and oxidized low-density lipoprotein (oxLDL). RESULTS: The primary analysis cohort included 4907 participants from 5 global-burden-of-disease regions (38% female, 48% Black, median age 50 years). In fully adjusted models for sCD14, female sex and White race (among those in high-income regions) were associated with higher sCD14 levels, while higher body mass index (BMI) and current use of nucleoside reverse transcriptase inhibitor + integrase strand transfer inhibitor ART were associated with lower sCD14 levels. In fully adjusted models for oxLDL, male sex, residence in high-income regions, White race (among those in high-income regions), and higher BMI were associated with higher oxLDL levels. In a subanalysis cohort of 1396 women with HIV, increased reproductive age was associated with higher sCD14 levels but not with higher oxLDL levels. CONCLUSIONS: Factors associated with sCD14 and oxLDL, 2 key indices of immune-mediated CVD risk, differ. Future studies will elucidate ways in which medications (eg, statins) and behavioral modifications influence sCD14 and oxLDL and the extent to which dampening of these markers mediates CVD-protective effects. CLINICAL TRIALS REGISTRATION: NCT0234429.
BACKGROUND: Among antiretroviral therapy (ART)-treated people with human immunodeficiency virus (PWH), persistent systemic immune activation contributes to atherogenesis atherosclerotic, cardiovascular disease (CVD) events, and mortality. Factors associated with key immune activation indices have not previously been characterized among a global primary CVD prevention cohort of PWH. METHODS: Leveraging baseline Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) data, we evaluated factors associated with soluble CD14 (sCD14) and oxidized low-density lipoprotein (oxLDL). RESULTS: The primary analysis cohort included 4907 participants from 5 global-burden-of-disease regions (38% female, 48% Black, median age 50 years). In fully adjusted models for sCD14, female sex and White race (among those in high-income regions) were associated with higher sCD14 levels, while higher body mass index (BMI) and current use of nucleoside reverse transcriptase inhibitor + integrase strand transfer inhibitor ART were associated with lower sCD14 levels. In fully adjusted models for oxLDL, male sex, residence in high-income regions, White race (among those in high-income regions), and higher BMI were associated with higher oxLDL levels. In a subanalysis cohort of 1396 women with HIV, increased reproductive age was associated with higher sCD14 levels but not with higher oxLDL levels. CONCLUSIONS: Factors associated with sCD14 and oxLDL, 2 key indices of immune-mediated CVD risk, differ. Future studies will elucidate ways in which medications (eg, statins) and behavioral modifications influence sCD14 and oxLDL and the extent to which dampening of these markers mediates CVD-protective effects. CLINICAL TRIALS REGISTRATION: NCT0234429.
Authors: J E Lake; G A McComsey; T Hulgan; C A Wanke; A Mangili; S L Walmsley; S A Stramotas; R Tracy; J S Currier Journal: HIV Med Date: 2014-02-10 Impact factor: 3.180
Authors: Sara E Looby; Kathleen V Fitch; Suman Srinivasa; Janet Lo; Danielle Rafferty; Amanda Martin; Judith C Currier; Steven Grinspoon; Markella V Zanni Journal: AIDS Date: 2016-01-28 Impact factor: 4.177
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: Mabel Toribio; Kathleen V Fitch; Laura Sanchez; Tricia H Burdo; Kenneth C Williams; Craig A Sponseller; Mary McCurdy Pate; Judith A Aberg; Markella V Zanni; Steven K Grinspoon Journal: AIDS Date: 2017-03-27 Impact factor: 4.177
Authors: Helen E Cejtin; Charlesnika T Evans; Ruth Greenblatt; Howard Minkoff; Kathleen M Weber; Rodney Wright; Christine Colie; Elizabeth Golub; L Stewart Massad Journal: J Womens Health (Larchmt) Date: 2018-09-14 Impact factor: 2.681
Authors: Eric Nou; Michael T Lu; Sara E Looby; Kathleen V Fitch; Elli A Kim; Hang Lee; Udo Hoffmann; Steven K Grinspoon; Janet Lo Journal: AIDS Date: 2016-02-20 Impact factor: 4.177
Authors: Chris T Longenecker; Milana Bogorodskaya; Seunghee Margevicius; Rashidah Nazzinda; Marcio Sommer Bittencourt; Geoffrey Erem; Sophie Nalukwago; Moises A Huaman; Brian B Ghoshhajra; Mark J Siedner; Steven M Juchnowski; David A Zidar; Grace A McComsey; Cissy Kityo Journal: J Int AIDS Soc Date: 2022-01 Impact factor: 5.396
Authors: Jordan E Lake; Ruibin Wang; Benjamin W Barrett; Emily Bowman; Ana N Hyatt; Paula Debroy; Jury Candelario; Linda Teplin; Kaitlin Bodnar; Heather McKay; Michael Plankey; Todd T Brown; Nicholas Funderburg; Judith S Currier Journal: AIDS Date: 2022-08-10 Impact factor: 4.632