Evolution of the serologic and virologic course of occult HBV infection in therapy experienced HIV co-infected patients

Abstract

We investigated how the natural course of occult hepatitis B virus (HBV) infection (OBI) may evolve during HIV co-infection and long term HBV-active HAART. From a cohort of 181 HIV infected patients who were consecutively recruited over a 5 year period, 28 HBV co-infected patients with sequential sera (n = 98) were identified. Iterative HBV serology and viral loads were determined before and during treatment. The viral HBsAg gene was then serially amplified, directly sequenced, and molecularly characterized. Persistent detection of anti-HBs did not result in a modification to the clinical course of OBI. In contrast, reactivation of chronic HBV infection, hepatic enzymatic flares and cases of HBV reinfection were evident among anti-HBs negative OBI patients, and this was a notable finding. Of the 14 chronic HBV infected patients, eight progressed to persistent OBI after initiation of HBV-active HAART, increasing the number of patients with OBI in the study. Long term HBV-active HAART was not found to have a notable impact on low level viremia during OBI. While the HBsAg gene sequences isolated from chronic HBV infection were genetically stable over time, OBI-associated variants (sP111R, sT127P, sY161F) were neither stable nor predominant during the course of infection. This study is the first of its kind from South Africa to show the occurrence of hepatic enzymatic flares, HBV reactivation, and reinfection in HAART-exposed HIV co-infected patients with OBI. Among the cases studied, there was further evidence that OBI-associated variants may not play a significant role in the pathogenesis of OBI.

Keywords: antiviral agents; genetic variability; hepatitis B virus; human immunodeficiency virus; reactivation; superinfection.