Persistent HBV replication and serological response during up to fifteen years of tenofovir-based antiretroviral therapy in HIV-hepatitis B coinfected patients: a multicenter prospective cohort study

Objectives To determine the extent of hepatitis B virus (HBV) suppression and its association with hepatitis “e” antigen (HBeAg) and hepatitis B surface antigen (HBsAg)-seroclearance in HIV-HBV-coinfected patients undergoing long-term tenofovir (TDF)-based antiretroviral therapy (ART). Methods We prospectively followed 165 HIV-HBV-coinfected patients undergoing TDF-based ART. Serum HBV-DNA viral loads, HBeAg and HBsAg were obtained at TDF-initiation and every 6-12 months. We calculated the proportion achieving virological response (VR, <60 IU/mL) during follow-up. We also calculated rates of HBeAg- and HBsAg-seroclearance, which were compared between those who achieved versus never achieved VR during follow-up using an exact binomial test. Results During a median 8.1 years (IQR=4.0-13.2) of TDF-treatment, 152 (92.1%) patients were able to achieve VR and 13 (7.9%) never achieved VR (median HBV-DNA at the end of follow-up=608 IU/mL, range=67-52,400,000). The prevalence of individuals with detectable HBV-DNA (≥60 IU/mL) decreased during TDF-treatment: 15.1% ( n =14/93) at 5-years, 3.2% ( n =2/62) at 10-years and, 3.2% ( n =1/31) at 15-years. 44/96 HBeAg-positive patients (6.15/100 person-years) had HBeAg-seroclearance and 13/165 patients overall (0.87/100 person-years) had HBsAg-seroclearance. No difference in HBeAg-seroclearance was observed between those who achieved versus never achieved VR (7.4 versus 3.7/100 person-years, p =0.33), while HBsAg-seroclearance was only observed in those with VR (1.0 versus 0/100 person-years, p =0.49; respectively). Individuals with VR also had a higher frequency of undetectable HIV-RNA during treatment (p<0.001). Conclusions During long-term TDF-based ART for HIV-HBV coinfection, persistent HBV viremia is apparent, but becomes less frequent over time. HBsAg-seroclearance only occurred in those with full HBV and relatively high HIV suppression. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by SIDACTION (AO 19) and the ANRS. Gilead Sciences, Inc. provided an unrestricted grant for the French HIV-HBV cohort and was not involved in any part of the design, data collection, analysis and manuscript writing. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All patients provided written informed consent to participate in the study and the protocol was approved by an appropriate Hospital Ethics Committee (Commite de protection des personnes (CPP) Pitie-Salpetriere, CPP Saint-Antoine et CPP Hotel Dieu; Paris, France) in accordance with the Helsinki Declaration. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes A full list of data citations are available by contacting the corresponding author.