Subclinical and Clinical Outcomes in Patients Coinfected With HIV and Chronic Hepatitis B Virus From Clinical Outpatient Centers in France: Protocol for an Ambispective, Longitudinal Cohort Study

Abstract

Background Previous large-scale studies have examined the effect of chronic hepatitis B virus (HBV) infection on overall and cause-specific mortality in individuals with HIV. However, few studies have collected data on the subclinical indicators of HBV that lead to these severe outcomes in the coinfected population. Objective In this study, we aim to describe the procedures of a cohort study extension aimed at assessing HBV-DNA replication, serological markers of HBV (hepatitis B e antigen [HBeAg] and hepatitis B surface antigen), and liver fibrosis and how these subclinical outcomes relate to mortality in predominately tenofovir-treated, coinfected patients with HIV-HBV. We assessed the characteristics at cohort inclusion of those who participated in the cohort extension, as well as those who did not participate due to being lost to follow-up or death. Methods Patients with HIV and chronic HBV who completed follow-up in a prospective cohort study conducted in 4 outpatient centers (Paris and Lyon, France; 2002-2011) were invited to participate in a cross-sectional visit from November 2016 to March 2018, during which a comprehensive evaluation of HIV- and HBV-related disease was undertaken. Virological and clinical data since the previous study visit were retrospectively collected. Results Of the 308 individuals enrolled in the cohort, 147 (47.7%) participated in the cross-sectional study. At this visit, most participants were HBeAg negative (111/134, 82.8% with available data), had undetectable HBV DNA (124/132, 93.9% with available data), and were undergoing antiretroviral therapy containing tenofovir disoproxil fumarate or tenofovir alafenamide (114/147, 77.6%). There were no significant differences in characteristics at cohort inclusion between those who did and did not complete the cross-sectional visit, except for a lower proportion with an AIDS-defining illness (30/147, 20.5% vs 49/161, 30.4%, respectively; P=.04). Of the 161 nonparticipating individuals, 42 (26.1%) died, 41 (25.4%) were lost to follow-up and known to be alive, and 78 (48.4%) were lost to follow-up with unknown vital status. Most differences in characteristics at cohort inclusion were observed between deceased individuals and those participating in the cross-sectional visit or those lost to follow-up. With this extension, the median follow-up time of the overall cohort is presently 9.2 years (IQR 3.4-14.6). Conclusions Extended follow-up of the French HIV-HBV cohort will provide important long-term data on the subclinical trajectory of HBV disease in the coinfected population. The biases due to the relatively high rate of those lost to follow-up need to be assessed in future studies of this cohort. International Registered Report Identifier (IRRID) DERR1-10.2196/24731