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. We excluded those with prior antiviral treatment experience or HBV diagnosis due to clinical suspicion (rather than routine testing). We assessed HBV DNA levels, hepatitis B e antigen (HBeAg), CD4+ (if HIV coinfection), and liver disease (transient elastography, 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% were male, and 433 had HBV/HIV coinfection. Median CD4+ count was 200 cells/μl. HBV DNA was greater than 2000 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 five-fold increased HBV DNA levels [adjusted geometric mean ratio, 5.78; 95% confidence interval (CI), 2.29–14.62] and two 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/μl. 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.