Kinetics and predictors of Hepatitis B surface antigen (HBsAg) loss after commencing HBV-active antiretroviral therapy (ART) in the setting of HIV-and chronic HBV co-infection

Jennifer Audsley; Anchalee Avihingsanon; Xin Li; Rosalind Edwards; Kathy Jackson; Nadia Warner; Olivia Maslac; Peter Revill; Hay Mar Su Lwin; Sivaporn Gatechompol; Nagalingeswaran Kumarasamy; Tim Spelman; Iskandar Azwa; Adeeba Kamarulzaman; Sharon R Lewin; Joe Sasadeusz

doi:10.1093/cid/ciaf281

Kinetics and predictors of Hepatitis B surface antigen (HBsAg) loss after commencing HBV-active antiretroviral therapy (ART) in the setting of HIV-and chronic HBV co-infection

Clin Infect Dis. 2025 May 31:ciaf281. doi: 10.1093/cid/ciaf281. Online ahead of print.

Authors

Jennifer Audsley¹, Anchalee Avihingsanon², Xin Li³, Rosalind Edwards³, Kathy Jackson³, Nadia Warner³, Olivia Maslac³, Peter Revill^{1

3}, Hay Mar Su Lwin², Sivaporn Gatechompol², Nagalingeswaran Kumarasamy⁴, Tim Spelman^{5

6

7}, Iskandar Azwa⁸, Adeeba Kamarulzaman⁸, Sharon R Lewin^{1

9

10}, Joe Sasadeusz^{1

9

10}

Affiliations

¹ Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne Australia.
² HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Thai Red Cross AIDS Research Centre, and Center of Excellence in Tuberculosis, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
³ Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
⁴ Infectious Diseases Medical Centre, Voluntary Health Services Hospital, Chennai, India.
⁵ Burnet Institute, Melbourne, Australia.
⁶ University of Adelaide, Adelaide, Australia.
⁷ Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
⁸ Infectious Diseases Unit, Department of Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia.
⁹ Victorian Infectious Diseases Service, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
¹⁰ Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia.

PMID: 40447285
DOI: 10.1093/cid/ciaf281

Abstract

Background: An effective therapeutic strategy for HBV cure remains an urgent unmet need. We aimed to define the incidence, kinetics and predictors of hepatitis B surface antigen (HBsAg) loss in people living with HIV and HBV (PLWH-HBV) following HBV-active antiretroviral therapy (ART) in PLWH-HBV in Asia.

Method: 97 PLWH-HBV commencing HBV-active ART were recruited prospectively in Thailand (n=94) and Malaysia (n=3) then followed for 24 months. Time to HBV serology change was calculated. Univariate associations between baseline characteristics and HBsAg loss were examined using the Mann-Whitney or Chi-square tests. Multivariable analysis was undertaken using Cox regression.

Results: 21 individuals (22%) lost HBsAg during follow-up (11.7 per 100 PY), 14 of whom gained anti-HBs. 22/61 (36.1%) individuals who were hepatitis B "e" antigen (HBeAg) positive at baseline lost HBeAg over the study, 15 of whom gained anti-HBe. Most individuals lost HBsAg and HBeAg by the month 12 study visit (81% and 63.6%, respectively), with median times of 5.8 and 12.0 months to HBsAg and HBeAg loss, respectively. Univariate analysis showed baseline characteristics associated with HBsAg loss were higher alanine aminotransferase (ALT, p=0.005), tenofovir alafenamide (TAF)-containing ART regimen (p=0.025), younger age (p=0.040), lower liver stiffness (p=0.010) and quantitative HBsAg< log102.0 IU/ml (p=0.001). All 5 factors remained significant in a Cox regression analysis that adjusted for baseline CD4 count.

Conclusions: High HBsAg loss rates occur in people living with HIV and HBV early after commencing ART. Our study suggests that TAF-containing ART regimens may be preferable as first line therapy in HIV-HBV co-infection.

Keywords: HBsAg loss; HIV-HBV co-infection; antiretroviral therapy.