Tenofovir (TDF) is effective in suppressing HIV and HBV replication in HIV/HBV co-infection. HBV DNA can persist in some individuals on TDF-containing combination antiretroviral therapy (ART) but HBV resistance to TDF has not been reported to date. We initiated this study to identify novel HBV mutations in HIV-HBV co-infected individuals receiving TDF, and determine risk factors associated with detectable HBV DNA on TDF.
We enrolled 93 HIV-HBV co-infected participants on, or about to commence, TDF containing ART in a prospective longitudinal study. Subjects were followed every 6 months with clinical and laboratory assessments. HBV polymerase sequencing was performed on plasma samples with an HBV DNA >400 IU/ml.
Study entry median age was 43 (IQR 38-50) years, the cohort was predominantly male (80%) and HBeAg positive (75.5%). At enrolment most patients were on TDF (92.4%) with median duration on TDF of 2.03 (IQR 1.0-4.4) years. Over 24 months of f/up, HBV DNA was persistently <15 IU/ml in 79.3% (n=73); >15 IU/ml once in 10.9% (n=10); and on >1 occasion in 7.6% (n=7; median number of occasions = 3 (IQR 2-5). Eight patients with detectable HBV DNA once during f/up had HBV DNA <15 IU/ml at enrolment. Three patients (3.3%) were adherent to ART but had persistently detectable HBV DNA during f/up. Univariate analysis demonstrated that positive HBeAg (p<0.01), detectable HBV DNA at enrolment (p<0.01) and country of recruitment (Australia, p=0.01) were associated with detectable HBV DNA on-TDF. In all plasma samples that underwent HBV sequencing (n=19), no novel HBV pol mutations were identified.
Detection of HBV DNA on more than one occasion in HIV-HBV co-infected patients on TDF containing cART is not uncommon, however, drug resistance did not occur in this setting. Prolonged follow up will be needed to determine the clinical significance of detectable HBV DNA on HBV-active ART.