Brandilyn A Peters1, Xiaonan Xue1, Lila A Sheira2, Qibin Qi1, Anjali Sharma3, Nanette Santoro4, Maria L Alcaide5, Igho Ofotokun6, Adaora A Adimora7, Heather S McKay8, Phyllis C Tien9,10, Katherine G Michel11, Deborah Gustafson12, Bulent Turan13, Alan L Landay14, Robert C Kaplan1,15, Sheri D Weiser2,10. 1. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA. 2. Division of HIV, Infectious Diseases, and Global Medicine, University of California San Francisco, San Francisco, California, USA. 3. Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA. 4. Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, Colorado, USA. 5. Division of Infectious Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA. 6. Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, Georgia, USA. 7. School of Medicine and Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. 8. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. 9. Department of Veterans Affairs Medical Center, San Francisco, California, USA. 10. Department of Medicine, University of California San Francisco, San Francisco, California, USA. 11. Department of Medicine, Georgetown University Medical Center, Washington, District of Colombia, USA. 12. Department of Neurology, State University of New York Downstate Health Sciences University, Brooklyn, New York, USA. 13. Department of Psychology, University of Alabama at Birmingham, Birmingham, Alabama, USA. 14. Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA. 15. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Abstract
BACKGROUND: Persistent immune activation due to gut barrier dysfunction is a suspected cause of morbidity in HIV, but the impact of menopause on this pathway is unknown. METHODS: In 350 women with HIV from the Women's Interagency HIV Study, plasma biomarkers of gut barrier dysfunction (intestinal fatty acid binding protein; IFAB), innate immune activation (soluble CD14 and CD163; sCD14, sCD163), and systemic inflammation (interleukin-6 and tumor necrosis factor receptor 1; IL-6, TNFR1) were measured at 674 person-visits spanning ≤2 years. RESULTS: Menopause (post- vs premenopausal status) was associated with higher plasma sCD14 and sCD163 in linear mixed-effects regression adjusting for age and other covariates (β = 161.89 ng/mL; 95% confidence interval [CI], 18.37-305.41 and 65.48 ng/mL, 95% CI, 6.64-124.33, respectively); but not with plasma IFAB, IL-6, or TNFR1. In piece-wise linear mixed-effects regression of biomarkers on years before/after the final menstrual period, sCD14 increased during the menopausal transition by 250.71 ng/mL per year (95% CI, 16.63-484.79; P = .04), but not in premenopausal or postmenopausal periods. CONCLUSIONS: In women with HIV, menopause may increase innate immune activation, but data did not support an influence on the gut barrier or inflammation. Clinical implications of immune activation during menopausal transition warrant further investigation.
BACKGROUND: Persistent immune activation due to gut barrier dysfunction is a suspected cause of morbidity in HIV, but the impact of menopause on this pathway is unknown. METHODS: In 350 women with HIV from the Women's Interagency HIV Study, plasma biomarkers of gut barrier dysfunction (intestinal fatty acid binding protein; IFAB), innate immune activation (soluble CD14 and CD163; sCD14, sCD163), and systemic inflammation (interleukin-6 and tumor necrosis factor receptor 1; IL-6, TNFR1) were measured at 674 person-visits spanning ≤2 years. RESULTS: Menopause (post- vs premenopausal status) was associated with higher plasma sCD14 and sCD163 in linear mixed-effects regression adjusting for age and other covariates (β = 161.89 ng/mL; 95% confidence interval [CI], 18.37-305.41 and 65.48 ng/mL, 95% CI, 6.64-124.33, respectively); but not with plasma IFAB, IL-6, or TNFR1. In piece-wise linear mixed-effects regression of biomarkers on years before/after the final menstrual period, sCD14 increased during the menopausal transition by 250.71 ng/mL per year (95% CI, 16.63-484.79; P = .04), but not in premenopausal or postmenopausal periods. CONCLUSIONS: In women with HIV, menopause may increase innate immune activation, but data did not support an influence on the gut barrier or inflammation. Clinical implications of immune activation during menopausal transition warrant further investigation.
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