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 AMBITION-CM study which enrolled adult PLWH with CM in Botswana (2018-2021) we screened for HBV surface antigen (HBsAg), viral load (VL), Occult Hepatitis B infection (HBsAg- & 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-&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.