Title: Antiretroviral therapy for HIV and intrahepatic hepatitis C virus replication

Abstract

HIV alters host responses to hepatitis C virus (HCV). However, the impact of antiretroviral therapy (ART) on HCV is rarely understood in relevant tissues and never before within individual hepatocytes. HIV and HCV kinetics were studied before and after ART initiation among 19 HIV/HCV co-infected persons. From five persons with the largest decline in plasma HCV RNA, liver tissues collected before and during ART, when plasma HIV RNA was undetectable, were studied. Here we used single-cell laser capture microdissection and quantitative PCR to assess intrahepatic HCV. Immunohistochemistry was performed to characterize intrahepatic immune cell populations. Plasma HCV RNA declined by 0.81 (0.52–1.60) log₁₀ IU/ml from a median (range) 7.26 (6.05–7.29) log₁₀ IU/ml and correlated with proportions of HCV-infected hepatocytes (r = 0.89, P = 2 × 10^-5), which declined from median (range) of 37% (6–49%) to 23% (0.5–52%) after plasma HIV clearance. Median (range) HCV RNA abundance within cells was unchanged in four of five participants. Liver T-cell abundance unexpectedly decreased, whereas natural killer (NK) and NK T-cell infiltration increased, correlating with changes in proportions of HCV-infected hepatocytes (r = -0.82 and r = -0.73, respectively). Hepatocyte expression of HLA-E, an NK cell restriction marker, correlated with proportions of HCV-infectedmore » hepatocytes (r = 0.79). These are the first data to show that ART control of HIV reduces the intrahepatic burden of HCV. Furthermore, our data suggest that HIV affects the pathogenesis of HCV infection by an NK/NK T-cell-mediated mechanism that may involve HLA-E and can be rescued, at least in part, by ART.« less

Authors:

Quinn, Jeffrey R. ^[1]; Goyal, Ashish ^[2]; Ribeiro, Ruy M.  ^[2];

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Massaccesi, Guido ^[1]; Bailey, Justin R. ^[1]; Thomas, David L. ^[1]; Balagopal, Ashwin ^[1]

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+ Show Author Affiliations

1. Johns Hopkins Medical Institutions, Baltimore, MD (United States)
2. Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

Publication Date:

Tue Mar 01 00:00:00 EST 2022

Research Org.:

Argonne National Lab. (ANL), Argonne, IL (United States)

Sponsoring Org.:

USDOE; National Institutes of Health (NIH)

OSTI Identifier:

1963639

Report Number(s):

LA-UR-21-31059
Journal ID: ISSN 0269-9370

Grant/Contract Number:  

89233218CNA000001; R37 DA013806; R01 AI116868

Resource Type:

Accepted Manuscript

Journal Name:

AIDS

Additional Journal Information:

Journal Volume: 36; Journal Issue: 3; Journal ID: ISSN 0269-9370

Publisher:

Wolters Kluwer Health, Inc.

Country of Publication:

United States

Language:

English

Subject:

60 APPLIED LIFE SCIENCES; HCV; HIV; liver; LCM; interferon; antiretroviral therapy