TY - JOUR
T1 - Effect of Viral Replication and Liver Fibrosis on All-Cause Mortality in Human Immunodeficiency Virus-Hepatitis B Virus-Coinfected Individuals
T2 - A Retrospective Analysis of a 15-Year Longitudinal Cohort
AU - Dezanet, Lorenza N.C.
AU - Kassime, Raisha
AU - Miailhes, Patrick
AU - Lascoux-Combe, Caroline
AU - Chas, Julie
AU - Maylin, Sarah
AU - Gabassi, Audrey
AU - Rougier, Hayette
AU - Delaugerre, Constance
AU - Lacombe, Karine
AU - Boyd, Anders
N1 - Publisher Copyright: © 2021 The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
PY - 2022/3/15
Y1 - 2022/3/15
N2 - Background: In individuals living with human immunodeficiency virus (HIV) and hepatitis B virus (HBV), widespread tenofovir (TDF)-containing antiretroviral therapy (ART) has led to substantial decreases in HBV-DNA and HIV-RNA detection. However, the links between viral replication, liver fibrosis, and mortality remain unclear. Methods: A total of 300 individuals living with HIV-HBV and undergoing ART were prospectively followed. Virological and clinical data were obtained at baseline and every 6-12 months. We quantified the associations between HBV-DNA, HIV-RNA, and liver fibrosis with risk of all-cause mortality using a joint longitudinal survival model. Viral detection, viral loads, and time-averaged cumulative viral loads of HIV and HBV were modeled as 3 separate exposures. Results: During a median of 10.5 years (interquartile range, 4.0-14.6), the proportion undergoing TDF-containing ART (baseline = 18.7%, end of follow-up = 79.1%) and with undetectable HBV-DNA (baseline = 36.7%, end of follow-up = 94.8%) substantially increased. 42 participants died (incidence rate = 1.30/100 person-years, 95% confidence interval [CI] =. 96-1.76). The leading causes of death were non-AIDS/non-liver-related malignancies (28.6%), followed by liver-related (16.7%), AIDS-related (16.7%), and other (16.7%). All-cause mortality was associated with HBV-DNA viral load (adjusted hazards ratio [aHR] per log10 IU/mL=1.41, 95% CI=1.04-1.93, P=.03) or time-averaged cumulative HBV-DNA (aHR per log10 copy-years=1.37, 95% CI=1.03-1.83, P=.03), but not undetectable HBV-DNA. Advanced liver fibrosis at baseline was also associated with increased mortality rates (aHR=2.35, 95% CI=1.16-4.76, P=.02). No significant association between HIV-RNA replication and mortality was observed. Conclusions: Concurrent and historical HBV replication and liver fibrosis are important drivers of all-cause mortality in largely TDF-treated individuals living with HIV-HBV, despite one-fifth of deaths being liver-related. HBV-DNA and liver fibrosis remain important prognostic indicators for this patient population.
AB - Background: In individuals living with human immunodeficiency virus (HIV) and hepatitis B virus (HBV), widespread tenofovir (TDF)-containing antiretroviral therapy (ART) has led to substantial decreases in HBV-DNA and HIV-RNA detection. However, the links between viral replication, liver fibrosis, and mortality remain unclear. Methods: A total of 300 individuals living with HIV-HBV and undergoing ART were prospectively followed. Virological and clinical data were obtained at baseline and every 6-12 months. We quantified the associations between HBV-DNA, HIV-RNA, and liver fibrosis with risk of all-cause mortality using a joint longitudinal survival model. Viral detection, viral loads, and time-averaged cumulative viral loads of HIV and HBV were modeled as 3 separate exposures. Results: During a median of 10.5 years (interquartile range, 4.0-14.6), the proportion undergoing TDF-containing ART (baseline = 18.7%, end of follow-up = 79.1%) and with undetectable HBV-DNA (baseline = 36.7%, end of follow-up = 94.8%) substantially increased. 42 participants died (incidence rate = 1.30/100 person-years, 95% confidence interval [CI] =. 96-1.76). The leading causes of death were non-AIDS/non-liver-related malignancies (28.6%), followed by liver-related (16.7%), AIDS-related (16.7%), and other (16.7%). All-cause mortality was associated with HBV-DNA viral load (adjusted hazards ratio [aHR] per log10 IU/mL=1.41, 95% CI=1.04-1.93, P=.03) or time-averaged cumulative HBV-DNA (aHR per log10 copy-years=1.37, 95% CI=1.03-1.83, P=.03), but not undetectable HBV-DNA. Advanced liver fibrosis at baseline was also associated with increased mortality rates (aHR=2.35, 95% CI=1.16-4.76, P=.02). No significant association between HIV-RNA replication and mortality was observed. Conclusions: Concurrent and historical HBV replication and liver fibrosis are important drivers of all-cause mortality in largely TDF-treated individuals living with HIV-HBV, despite one-fifth of deaths being liver-related. HBV-DNA and liver fibrosis remain important prognostic indicators for this patient population.
KW - HIV
KW - hepatitis B virus
KW - joint models
KW - mortality
KW - tenofovir
UR - http://www.scopus.com/inward/record.url?scp=85111573886&partnerID=8YFLogxK
U2 - https://doi.org/10.1093/cid/ciab594
DO - https://doi.org/10.1093/cid/ciab594
M3 - Article
C2 - 34197574
SN - 1058-4838
VL - 74
SP - 1012
EP - 1021
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 6
ER -