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Abstract Details
HCV DAA Therapy in Persons With HIV-HCV Genotype 1 Coinfection Results in High Rate of Sustained Virologic Response and Heterogeneity in Normalization of Soluble Markers of Immune Activation
J Infect Dis. 2020 May 15;jiaa254.doi: 10.1093/infdis/jiaa254. Online ahead of print.
Donald D Anthony1, Mark S Sulkowski2, Laura M Smeaton3, Sofi Damjanovska1, Carey L Shive1, Corinne M Kowal1, Daniel E Cohen4, Debika Bhattacharya5, Beverly L Alston-Smith6, Ashwin Balagopal2, David L Wyles7
Author information
1Departments of Medicine and Pathology, VA Medical Center and MetroHealth Medical Center, Case Western Reserve University, ACTG Immunology Support Laboratory, Cleveland OH.
2Johns Hopkins University School of Medicine, Baltimore, MD.
3Harvard TH Chan School of Public Health.
4AbbVie Inc., North Chicago, IL.
5Division of Infectious Diseases, Department of Medicine David Geffen School of Medicine at UCLA.
6DAIDS, National Institutes of Health, Bethesda, MD.
7University of Colorado School of Medicine, Denver, CO
Abstract
Background: Hepatitis-C virus (HCV) direct-acting antivirals (DAAs) are highly effective. Less is known about changes in markers of immune activation in persons with HIV who achieve sustained virologic response (SVR).
Methods: We conducted a non-randomized clinical trial of 12 or 24 weeks of paritaprevir/ritonavir-ombitasvir-dasabuvir (PrOD)+/-ribavirin in persons with HCV-1/HIV co-infection suppressed with antiretroviral therapy (ART) [NCT02194998]. Plasma HCV, sCD14, IP10, sCD163, IL-6, IL-18, MCP1, Autotaxin (ATX), and Mac2-Binding-Protein (Mac2BP) were measured over 48-weeks.
Results: Participants were treated with PrOD 12 (n=9) or 24 (n=36) weeks; SVR12 rate was 93%. At baseline, cirrhosis associated with higher ATX and MCP1, women had higher ATX and IL-6, older age associated with higher Mac2BP, higher BMI associated with higher ATX, and HIV-1 protease inhibitor use associated with higher sCD14. In those with SVR, IP-10, ATX, and Mac2BP declined by week 2, IL-18 declined by end-of-treatment, sCD14 did not change, and sCD163, MCP1 and IL-6 levels changed at a single time point.
Conclusions: During HIV/HCV co-infection plasma immune activation marker heterogeneity is in-part attributable to age, sex, cirrhosis, BMI and/or type of antiretroviral therapy. HCV treatment with PrOD is highly effective, and associated with variable rate and magnitude of decline in markers of immune activation.