Research Article: Higher rates of HBsAg clearance with tenofovir-containing therapy in HBV/HIV co-infection

Date Published: April 18, 2019

Publisher: Public Library of Science

Author(s): Pierre Gantner, Laurent Cotte, Clotilde Allavena, Firouzé Bani-Sadr, Thomas Huleux, Claudine Duvivier, Marc-Antoine Valantin, Christine Jacomet, Véronique Joly, Antoine Chéret, Pascal Pugliese, Pierre Delobel, André Cabié, David Rey, Jee-Fu Huang.

http://doi.org/10.1371/journal.pone.0215464

Abstract

Achieving functional cure of chronic HBV infection (Hepatitis B surface antigen [HBsAg] clearance, eventually followed by acquisition of anti-hepatitis B surface antigen [Anti-HBs]) in individuals with HIV and HBV infections is a rare event. In this setting, factors related to HBV cure have not yet been fully characterized.

HIV-infected individuals with chronic HBV infection enrolled in the French Dat’AIDS cohort (NCT02898987), who started combined antiretroviral (cART)-anti-HBV treatment were retrospectively analyzed for HBsAg loss and Anti-HBs seroconversion.

Overall, 1419 naïve-subjects received three different cART-anti-HBV treatment schedule: (1) 3TC or FTC only (n = 150), (2) TDF with or without 3TC or FTC (n = 489) and (3) 3TC or FTC as first line followed by adding/switching to TDF as second line (n = 780). Individuals were followed-up for a median of 89 months (IQR, 56–118). HBV-DNA was < 15 IU/mL in 91% of individuals at the end of the follow-up. Overall, 97 individuals cleared HBsAg (0.7/100 patient-years), of whom, 67 seroconverted for Anti-HBs (0.5/100 patient-years). A high CD4 nadir, a short delay between HBV diagnosis and treatment, a longer time on HBV therapy, an African origin and TDF-based therapy were independent predictors of HBsAg clearance (Probability of odds ratio [OR]>1, >95%) suggested by Bayesian analysis. Also, TDF-based regimen as first line (OR, 3.03) or second line (OR, 2.95) increased rates of HBsAg clearance compared to 3TC or FTC alone, with a 99% probability.

HBsAg clearance rate was low in HIV-HBV co-infected cART-anti-HBV treated individuals, but was slightly improved on TDF-based regimen.

Partial Text

HIV-associated comorbidities remain one major public health challenge worldwide, despite the success of combined antiretroviral therapy (ART) in controlling HIV viral load and in increasing life expectancy of people living with HIV. For instance, individuals with both chronic HBV and HIV infections have an increased risk of developing both cirrhosis and hepatocellular carcinoma, leading to heightened risk of mortality [1–2]. HIV-infected individuals are at higher risk of both acquiring HBV infection (due to the shared risk of transmission factors between the two viruses) and developing chronic hepatitis B (HBV) after acute infection [3]. In European countries, chronic hepatitis B marked by a positive Hepatitis B surface antigen (HBsAg) for at least 6 months is more prevalent in HIV-infected individuals (1 to 15%) [4–7] compared to uninfected individuals (< 1%) [8]. Based on HBV infection repartition worldwide, HBV prevalence ranges from 8.5 to 28% in HIV-infected individuals in Asia or Africa [4,9–10]. Of 59829 HIV-infected individuals enrolled in the Dat’AIDS cohort between 2006 and 2016, 1419 (2.4%) harbored HBsAg for at least 6 months, were cART-naive and subsequently initiated cART-anti-HBV treatment. Individuals received HBV therapy according to one of the following schemes: (1) 3TC or FTC only (n = 150), (2) TDF with or without 3TC or FTC (n = 489); and (3) 3TC or FTC as first line followed by adding/switching to TDF as second line with or without 3TC or FTC (n = 780). When analyzed by treatment regimen line: 930 individuals received 3TC or FTC as first line (individuals who only received 3TC or FTC only plus those who were on 3TC or FTC as first line before switching to TDF as second line), 489 individuals received TDF as first line and 780 received TDF as second line. Subjects were primarily male (76%), had a median age of 36 years at baseline, 90% acquired both HIV and HBV by sexual transmission, and 6% of them were co-infected with hepatitis D virus (Table 1). Median follow-up was of 89 months (IQR, 56–118) but varied among groups of individuals (Fig 1). HIV virological control was achieved in 96% of individuals at the end of follow-up. Chronic HBV co-infection burden among HIV-infected individuals results in higher rates of mortality compared to mono-infected subjects [1–2] This study in a real-life large cohort of HBV/HIV co-infected individuals showing that HBV functional cure rate remains very low, i.e., <1/100 patient-years under long term cART, including anti-HBV treatment.   Source: http://doi.org/10.1371/journal.pone.0215464

 

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