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

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

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

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Study flowchart.

Of 59829 HIV-infected individuals enrolled in the Dat’AIDS cohort between 2006 and 2016, 1419 harbored HBsAg for at least 6 months and subsequently initiated cART-anti-HBV treatment. Individuals received one of the following HBV therapy 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 with or without 3TC or FTC (n = 780). TDF, Tenofovir disoproxil fumarate; 3TC, lamivudine; FTC, emtricitabine.

Fig 2. Kaplan-Meier analysis of HBsAg clearance and anti-HBs seroconversion.

Kaplan-Meier analysis of HBsAg clearance on 1st line regimen (A): 3TC or FTC-based regimen (n = 930, corresponding to the addition of the follow-up of individuals who only received FTC or 3TC [n = 150], plus the first part of the follow-up of those who then switched to TDF containing regimen [780]), or TDF with or without 3TC or FTC-based regimen (n = 489); and 2nd line regimen (B): TDF with or without 3TC or FTC-based regimen (n = 780, corresponding to the second part of the follow-up of those who first received 3TC or FTC and then TDF). The corresponding Kaplan-Meier analyses of Anti-HBs seroconversion are depicted in (C) for 1st line regimen and (D) for 2nd line regimen. TDF, Tenofovir disoproxil fumarate; 3TC, lamivudine; FTC, emtricitabine.

Fig 3. Anti-HBs titers dynamic after seroconversion.

Evolution of Anti-HBs titers was depicted in the subset of 67 individuals who seroconverted for Anti-HBs on HBV therapy.