Development of chronic hepatitis B virus infection in hepatitis B surface antigen negative HIV/HBV co-infected adults: A rare opportunistic illness

Changes in serologic status in human immunodeficiency virus (HIV)/hepatitis B virus (HBV) co-infected individuals with either isolated anti-HBc or resolved HBV infection have been reported, but the frequency of clinically meaningful long-term serologic changes is not well-defined. This study therefore, examined longitudinal serologic status for hepatitis B surface antigen (HBsAg)-negative HIV/HBV co-infected participants in a large cohort. Among 5,222 cohort participants, 347 (7%) were initially isolated anti-HBc positive, and 1,073 (21%) had resolved HBV infection (concurrently reactive for anti-HBc and anti-HBs). Thirty-three (10%) of the 347 participants with isolated anti-HBc were later positive for HBsAg at least once, compared with 3 (0.3%) of those with resolved HBV (P<0.001). A total of 14 participants became persistently positive for HBsAg and were thus classified as having late-onset chronic HBV infection at a median of 3.7 years after initial HBV diagnosis. For those initially with HBsAg-negative HIV/HBV co-infection, the rate of late-onset chronic HBV infection was 1.39/1,000 person-years. Those with late-onset chronic HBV infection experienced significant decreases in CD4 cell counts (P=0.002) with a mean of 132cells/μl at the time of late-onset chronic HBV infection, but no factor distinguished those who were positive for HBsAg only once from those that developed late-onset chronic HBV infection. Over a median of 2.9 years following late-onset chronic HBV infection, 3 of 14 subsequently lost HBsAg. The occurrence of late-onset chronic HBV infection in HBsAg negative HIV/HBV co-infected adults appears to be one important, albeit rare, clinical event seen almost exclusively in those with isolated anti-HBc and low CD4 cell count.