Molecular Characterization of Hepatitis B Virus in People Living with HIV in Rural and Peri-Urban Communities in Botswana

Author:

Phinius Bonolo B.12ORCID,Choga Wonderful T.12ORCID,Anderson Motswedi134,Mokomane Margaret2,Gobe Irene2ORCID,Ratsoma Tsholofelo1,Phakedi Basetsana1,Mpebe Gorata1,Bhebhe Lynnette1ORCID,Gaolathe Tendani15,Mosepele Mosepele15,Makhema Joseph16,Shapiro Roger16,Lockman Shahin16,Musonda Rosemary16,Moyo Sikhulile12678ORCID,Gaseitsiwe Simani16

Affiliation:

1. Botswana Harvard Health Partnership, Gaborone Private Bag BO320, Botswana

2. School of Allied Health Professions, Faculty of Health Sciences, University of Botswana, Gaborone Private Bag UB0022, Botswana

3. Africa Health Research Institute (AHRI), Private Bag X7, Congella, Durban 4013, South Africa

4. The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK

5. Faculty of Medicine, University of Botswana, Gaborone Private Bag UB0022, Botswana

6. Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA

7. Division of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University, Private Bag X1, Matieland, Cape Town 7602, South Africa

8. School of Health Systems and Public Health, University of Pretoria, Private Bag X20, Pretoria 0028, South Africa

Abstract

(1) Background: Hepatitis B virus (HBV) sequencing data are important for monitoring HBV evolution. We aimed to molecularly characterize HBV sequences from participants with HBV surface antigen-positive (HBsAg+) serology and occult hepatitis B infection (OBI+). (2) Methods: We utilized archived plasma samples from people living with human immunodeficiency virus (PLWH) in Botswana. HBV DNA was sequenced, genotyped and analyzed for mutations. We compared mutations from study sequences to those from previously generated HBV sequences in Botswana. The impact of OBI-associated mutations on protein function was assessed using the Protein Variation Effect Analyzer. (3) Results: Sequencing success was higher in HBsAg+ than in OBI+ samples [86/128 (67.2%) vs. 21/71 (29.2%)]. Overall, 93.5% (100/107) of sequences were genotype A1, 2.8% (3/107) were D3 and 3.7% (4/107) were E. We identified 13 escape mutations in 18/90 (20%) sequences with HBsAg coverage, with K122R having the highest frequency. The mutational profile of current sequences differed from previous Botswana HBV sequences, suggesting possible mutational changes over time. Mutations deemed to have an impact on protein function were tpQ6H, surfaceV194A and preCW28L. (4) Conclusions: We characterized HBV sequences from PLWH in Botswana. Escape mutations were prevalent and were not associated with OBI. Longitudinal HBV studies are needed to investigate HBV natural evolution.

Funder

Wellcome Trust

Bill & Melinda Gates Foundation

National Institutes of Health

European & Developing Countries Clinical Trials Partnership

Centers for Disease Control and Prevention

Publisher

MDPI AG

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