Detection of hepatitis B virus in cerebrospinal fluid of people with HIV-associated cryptococcal meningitis in Botswana.

OBJECTIVES

To investigate hepatitis B virus presence in plasma and cerebrospinal fluid (CSF) of people living with HIV (PLWH) associated cryptococcal meningitis (CM) in Botswana.

METHODS

Baseline plasma and CSF samples from the AMBIsome Therapy Induction Optimization for CM study, which enrolled adult PLWH with CM in Botswana (2018-2021), were screened for HBV surface antigen (HBsAg), viral load, occult hepatitis B infection (HBsAg- and HBV DNA+), and sequenced the surface/polymerase region to assess mutations and genetic diversity.

RESULTS

Among 81 participants, 67.9% (55/81) were male, median age was 40 years (IQR: 34-44), median CD4+ T cell count was 29 cells/µl (IQR: 11-65). Available plasma (n = 77) and CSF (n = 74) samples were screened for HBV. Plasma HBsAg prevalence was 29.7% (95% CI: 20-42 (19/64) and 18.8% (95% CI: 10-30 (13/69) in CSF. Occult HBV infection (HBsAg- and HBV DNA+) was detected in 35.5% (95% CI: 21-53, 11/31) in plasma and 2.4% (95% CI: 0.06-13, 1/42) in CSF. ART exposure was associated with reduced plasma HBV DNA (P = 0.04), with no significant effect observed in CSF (P = 0.7). In plasma-CSF pairs, plasma showed higher detection rates for HBsAg, HBV DNA, and OBI (P ≤ 0.01). HBV was sequenced in 5 CSF and 4 plasma samples, including 3 pairs. Genotypes A and D detected were concordant between pairs, but 2 pairs showed mutational frequency discordance.

CONCLUSION

HBsAg and HBV DNA were detected in CSF of PLWH with CM, suggesting the CSF may be a reservoir.