Hepatitis B viral replication markers and hepatic fibrosis in untreated chronic hepatitis B virus infection with and without HIV coinfection in Zambia

Abstract

Background: To inform novel therapies, a more nuanced understanding of HIV's impact on hepatitis B virus (HBV) natural history is needed, particularly in high burden countries. Methods: In Lusaka, Zambia, we compared prospectively-recruited adults (18+ years) with chronic HBV infection, with and without HIV, pre-therapy. We excluded those with treatment-experience or HBV diagnosis due to clinical suspicion. We assessed HBV DNA levels, hepatitis B e antigen, CD4 (if coinfection), and liver disease (transient elastography [TE], serum alanine aminotransferase). In multivariable analyses, we evaluated the association of HIV overall and by level of CD4 count on these markers. Results: Among 713 adults analyzed, median age was 33 years, 63.0% were male, and 433 had HBV/HIV coinfection. Median CD4 count was 200 cells/mm3. HBV DNA was >2,000 IU/ml for 311 (51.0%) and 227 (32.5%) were HBeAg-positive. 15.5% had advanced fibrosis or cirrhosis. HIV coinfection was associated with 5-fold increased HBV DNA levels (adjusted geometric mean ratio, 5.78; 95% confidence interval, 2.29–14.62) and 2 times the odds of HBeAg-positivity (adjusted odds ratio, 2.54; 95% CI, 1.59–4.08). These associations were significant only at CD4 counts 100–350 and <100 cells/mm3. HIV was not associated with markers of fibrosis or ALT. Discussion: HIV's impact on HBV natural history likely depends on the degree and duration of immune suppression. There is strong rationale to monitor HBV DNA in people with HBV/HIV coinfection and immune suppression. A better understanding is needed of mechanisms of increased liver-related mortality in people with HBV/HIV coinfection.