High prevalence of HBV drug resistance mutations and genotypic diversity in HIV-positive South Africans.

ABSTRACT

¹Magada EF,
²Selabe SG ,
³Simani OE ,
⁴Modise LM

¹HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University, Pretoria 0208, South Africa
²HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University, Pretoria 0208, SA
³HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University, Pretoria 0208, SA
⁴HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University, Pretoria 0208, SA

Background

Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) are both endemic in South Africa, with co-infection posing serious health challenges. Although nucleoside analogs have improved HBV treatment, the emergence of drug-resistance strains remains a concern. This study aimed to determine the prevalence and characterize HBV drug resistance mutations in HIV-positive individuals

Method

This study analysed 144 archived serum samples from HIV-positive individuals collected between 2021 and 2023. Samples were categorized based on their hepatitis B surface antigen (HBsAg) status, with 50.7% testing positive and 49.3% testing negative for HBsAg. HBV DNA was extracted and analysed using a series of molecular techniques targeting the polymerase gene, including real-time PCR, nested PCR and Sanger sequencing, to identify resistance mutations.

Result

Genotyping showed a diverse distribution of HBV genotypes, including A, D, E G and A/G with genotype A being the most prevalent. Mutational analysis revealed a high prevalence of genetic variability, with drug resistance mutations detected in 92% of the sequences. Eighteen distinct drug resistance mutations were identified, with mutations rtI253V, rtM129L and rtV163I being the most prevalent. The identified mutations conferred resistance to multiple antiviral agents, including lamivudine (3TC), tenofovir (TDF), adefovir (ADV), entecavir (ETV), and telbivudine (LdT), with respective resistance prevalence of 66.7% (12/18), 61.1% (11/18), 27.8% (5/18), 22.2% (4/18), and 16.7% (3/18). The ‘YMDD’ motif was highly conserved in most study sequences, with the point mutation rtM204V being detected in 1.4% (1/69). Compensatory mutations rtL180M and rtV173A/G were reported in 1.4% (1/69) and 14.5% (10/69) of the study sequences, respectively.

Conclusion

This study shows a concerning prevalence of HBV drug-resistant mutations in HIV co-infected individuals, along with the identification of diverse HBV genotypes which complicates treatment management. With 92.0% of sequences showing antiviral resistance mutations, ongoing surveillance is crucial to inform therapeutic strategies.

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PRESENTING AUTHOR

Ms. Ester Magada, Bachelor of Science (Hons) (Medical sciences) - University of Limpopo

MSc student, Sefako Makgatho Health Sciences University

Ester Magada is a Medical Scientist graduate and is about to complete her Master of Science in Medical Virology at Sefako Makgatho Health Sciences University. She currently serves as an intern medical scientist at the National Health Laboratory Service (NHLS). Her research investigates hepatitis B virus mutations associated with drug resistance in HIV-infected patients, employing molecular techniques such as PCR, sequencing and bioinformatics analysis. With a strong foundation in virology, diagnostics and research, she aims to contribute to population-specific approaches in infectious disease management and public health advancement in South Africa and beyond.

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