Persistence and risk factors of occult hepatitis B virus infections among antiretroviral therapy-naïve people living with HIV in Botswana

Motswedi Anderson; Bonolo B Phinius; Basetsana K Phakedi; Mbatshi Mudanga; Lynnette N Bhebhe; Girlie N Tlhabano; Patience Motshosi; Tsholofelo Ratsoma; Kabo Baruti; Gorata Mpebe; Wonderful T Choga; Richard Marlink; Dieter Glebe; Jason T Blackard; Sikhulile Moyo; Anna Kramvis; Simani Gaseitsiwe

doi:10.3389/fmicb.2024.1342862

Persistence and risk factors of occult hepatitis B virus infections among antiretroviral therapy-naïve people living with HIV in Botswana

Front Microbiol. 2024 May 9:15:1342862. doi: 10.3389/fmicb.2024.1342862. eCollection 2024.

Authors

Motswedi Anderson¹, Bonolo B Phinius^{1

2}, Basetsana K Phakedi¹, Mbatshi Mudanga³, Lynnette N Bhebhe¹, Girlie N Tlhabano¹, Patience Motshosi¹, Tsholofelo Ratsoma¹, Kabo Baruti^{1

4}, Gorata Mpebe¹, Wonderful T Choga^{1

2}, Richard Marlink^{1

5}, Dieter Glebe⁶, Jason T Blackard⁷, Sikhulile Moyo^{1

2

8

9

10}, Anna Kramvis¹¹, Simani Gaseitsiwe^{1

8}

Affiliations

¹ Research Laboratory, Botswana Harvard Health Partnership, Gaborone, Botswana.
² School of Allied Health Professions, Faculty of Health Sciences, University of Botswana, Gaborone, Botswana.
³ Botswana - University of Maryland School of Medicine Health Initiative, Gaborone, Botswana.
⁴ Department of Biological Sciences, Faculty of Science, University of Botswana, Gaborone, Botswana.
⁵ Rutgers Global Health Institute, Rutgers University, New Brunswick, NJ, United States.
⁶ Institute of Medical Virology, National Reference Centre for Hepatitis B Viruses and Hepatitis D Viruses, Justus Liebig University of Giessen, Giessen, Germany.
⁷ Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
⁸ Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
⁹ Division of Medical Virology, Faculty of Medicine and Health Sciences, University of Stellenbosch, Cape Town, South Africa.
¹⁰ School of Health Systems and Public Health, University of Pretoria, Pretoria, South Africa.
¹¹ Hepatitis Virus Diversity Research Unit, Department of Internal Medicine, School of Clinical Medicine, University of the Witwatersrand, Johannesburg, South Africa.

Abstract

Aim: This study aimed to determine the kinetics of occult hepatitis B virus infections (OBI) among people with HIV (PWH).

Methods: The study used archived plasma samples from longitudinal HIV natural history studies. We identified new OBI cases and assessed risk factors for OBI using Cox proportional hazards regression analysis.

Results: At baseline, 8 of 382 [(2.1%) (95% CI: 1.06-4.1)] samples tested positive for hepatitis B surface antigen (HBsAg⁺). Of the 374 HBsAg-negative samples, 76 had sufficient sample volume for HBV DNA screening. OBI positivity (OBI⁺) at baseline was reported in 11 of 76 [14.7 95% CI (8.3-24.1)] HBsAg-negative (HBsAg^-) participants. Baseline HBsAg-negative samples with sufficient follow-up samples (n = 90) were used for analysis of newly identified OBI cases. Participants contributed 129.74 person-years to the study and were followed for a median of 1.02 years (IQR: 1.00-2.00). Cumulatively, there were 34 newly identified OBI cases from the 90 participants, at the rate of 26.2/100 person-years (95% CI: 18.7-36.7). Newly identified OBI cases were more common among men than women (61.1% vs. 31.9%) and among participants with CD4⁺ T-cell counts ≤450 cells/mL (p-value = 0.02). Most of the newly identified OBI cases [55.9% (19/34)] were possible reactivations as they were previously HBV core antibody positive.

Conclusion: There was a high rate of newly identified OBI among young PWH in Botswana, especially in men and in participants with lower CD4⁺ T-cell counts. OBI screening in PWH should be considered because of the risk of transmission, possible reactivation, and risk factors for the development of chronic liver disease, including hepatocellular carcinoma.

Keywords: HBV; HIV/HBV, hepatitis B surface antigen (HBsAg) negative; OBI; hepatitis B virus; incidence; occult hepatitis B.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded in whole, or in part, by the Wellcome [grant number 218770/Z/19/Z] and SANTHE. For open access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission. MA and BBP were supported by Wellcome. SM was supported by NIH Fogarty International Centre (K43TW012350). SG, WC, and BBP were partially supported by Pan African Bioinformatics Network for the Human Heredity and Health in Africa (H3Africa) consortium (H3ABioNet) and grants from HHS/NIH/National Institute of Allergy and Infectious Diseases (NIAID) (5K24AI131928–04; 5K24AI131924–04) and National Institutes of Health Fogarty International Centre (D43TW009610-09S1). H3ABioNet is supported by the National Institutes of Health Common Fund [U41HG006941]. H3ABioNet is an initiative of the Human Health and Heredity in Africa Consortium (H3Africa) program of the African Academy of Science (AAS). SM and BBP were partially supported by the Trials of Excellence in Southern Africa (TESA III), which is part of the EDCTP2 program supported by the European Union (grant number CSA2020NoE-3104 TESAIII CSA2020NoE). SM was supported by Bill and Melinda Gates grant number INV-033558. We also thank the Ministry of Health and Wellness and the Botswana Harvard AIDS Institute Partnership for the resources they contributed toward the successful completion of this project. The funders had no role in the study design, data collection, and decision to publish, or in the preparation of the manuscript.