Virology and clinical sequelae of long-term antiviral therapy in a North American cohort of hepatitis B virus (HBV)/human immunodeficiency virus type 1 (HIV-1) co-infected patients

Abstract

There are limited recent data worldwide on clinical and virological outcomes in hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfected patients on dual active antiretroviral therapy (ART).

Methods: We completed a retrospective review of 53 coinfected patients. HBV DNA in plasma was tested by PCR (sensitivity <20-<55 IU/ml or ∼100-300 copies/ml, Roche Diagnostics). Quantitative hepatitis B surface antigen (qHBsAg) was measured by an in-house assay (calibration range 0.24-62.5 IU/ml). HBV genotyping was done by line probe assay, and HBV variants determined by sequencing the HBV polymerase (P)/overlapping surface (S) gene.

Results: There were 7% (4/53) non-liver related deaths, ∼11% (6/53) had >F2 fibrosis, including 3 with cirrhosis. The median CD4+ T cell count was 415 cells/mm(3) (range 60-1310). 54% (28/51) were HBeAg-positive, and 81% (43/53) on ART had undetectable HBV DNA but only 5% (3/51) lost HBeAg. In 11/53 with HBV sequencing, 90% (10/11) were found to have HBV genotype A (HBV-A) and/or 27% (3/11) had a mixed A/G infection. Anti-HBV drug resistant mutations were detected in 54% (6/11) (i.e., any combination of rtV173L, rtL180M, M204V) and 45% (5/11) had an immune escape mutation (sP120S). In 12 with qHBsAg testing, the majority (9/12) had low-level qHBsAg ∼1-3 log(10) IU/ml.

Summary: Liver disease occurs in ∼10% of coinfected patients on ART and many have low-level HBV DNA and qHBsAg. In those sequenced most were HBV-A or mixed A/G genotype, and several carry P and S mutants highlighting the complex molecular virology of HBV during HIV coinfection.