Julie A E Nelson1, Kristina De Paris, Catalina Ramirez, Andrew Edmonds, Katie R Mollan, Camden P Bay, Kara Compliment, Betsy C Herold, Kathryn Anastos, Howard Minkoff, Seble Kassaye, Dominika L Seidman, Audrey L French, Elizabeth T Golub, Anandi N Sheth, Christina Ochsenbauer, Ronald Swanstrom, Joseph J Eron, Adaora A Adimora. 1. UNC Center for AIDS Research Department of Microbiology and Immunology Department of Medicine Department of Biochemistry and Biophysics, School of Medicine Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina Departments of Pediatrics and Microbiology-Immunology Department of Medicine, Albert Einstein College of Medicine, Bronx Department of Obstetrics and Gynecology, Maimonides Medical Center, Brooklyn, New York Division of Infectious Diseases and Travel Medicine, Georgetown University, Washington, DC Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Francisco, California The Core Center, Cook County Health and Hospital System, Rush University Medical College, Chicago, Illinois Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Abstract
OBJECTIVE: Determine the frequency of genital HIV-1 shedding in a large cohort of women on long-term suppressive antiretroviral therapy (ART) and its association with mucosal inflammation. DESIGN: We measured levels of HIV-1 RNA and inflammation biomarkers in cervicovaginal lavage (CVL) from HIV-seropositive women enrolled in the Women's Interagency HIV Study (WIHS). METHODS: HIV-1 was quantified (Abbott RealTime HIV-1 assay) from CVL samples of 332 WIHS participants with and without clinical evidence of genital inflammation at the time of CVL collection; participants had suppressed plasma viral load (PVL; limit of quantitation less than 20-4000 copies/ml depending on year of collection) for a median of 7.1 years [interquartile range (IQR) 3.4-9.8, Group 1] or for a median of 1.0 years (IQR = 0.5-1.0, Group 2). Twenty-two biomarkers of inflammation were measured in CVL to compare with clinical markers. RESULTS: HIV-1 was detected in 47% of 38 pre-ART CVL samples (median 668 copies/ml) and detection in CVL was associated with higher pre-ART PVL. HIV-1 was detected in only 1 of 38 CVL samples from these women on suppressive antiretroviral therapy for 1 year. No HIV-1 RNA was detected in 294 CVL samples from a cross-sectional set of women with suppressed PVL for a median of 7 years. Clinical inflammation markers were correlated with inflammatory biomarkers in CVL specimens, although genital inflammation was not associated with measurable genital HIV-1 shedding in these WIHS participants on ART. CONCLUSION: ART that suppresses HIV-1 in the plasma of women also prevents genital tract HIV-1 shedding, even in the presence of genital tract inflammation.
OBJECTIVE: Determine the frequency of genital HIV-1 shedding in a large cohort of women on long-term suppressive antiretroviral therapy (ART) and its association with mucosal inflammation. DESIGN: We measured levels of HIV-1 RNA and inflammation biomarkers in cervicovaginal lavage (CVL) from HIV-seropositive women enrolled in the Women's Interagency HIV Study (WIHS). METHODS: HIV-1 was quantified (Abbott RealTime HIV-1 assay) from CVL samples of 332 WIHS participants with and without clinical evidence of genital inflammation at the time of CVL collection; participants had suppressed plasma viral load (PVL; limit of quantitation less than 20-4000 copies/ml depending on year of collection) for a median of 7.1 years [interquartile range (IQR) 3.4-9.8, Group 1] or for a median of 1.0 years (IQR = 0.5-1.0, Group 2). Twenty-two biomarkers of inflammation were measured in CVL to compare with clinical markers. RESULTS: HIV-1 was detected in 47% of 38 pre-ART CVL samples (median 668 copies/ml) and detection in CVL was associated with higher pre-ART PVL. HIV-1 was detected in only 1 of 38 CVL samples from these women on suppressive antiretroviral therapy for 1 year. No HIV-1 RNA was detected in 294 CVL samples from a cross-sectional set of women with suppressed PVL for a median of 7 years. Clinical inflammation markers were correlated with inflammatory biomarkers in CVL specimens, although genital inflammation was not associated with measurable genital HIV-1 shedding in these WIHS participants on ART. CONCLUSION: ART that suppresses HIV-1 in the plasma of women also prevents genital tract HIV-1 shedding, even in the presence of genital tract inflammation.
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