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Hepatitis B virus drug resistance mutations in HIV/HBV co-infected children in Windhoek, Namibia

Abstract:
In patients who are HIV infected, hepatitis B virus (HBV) infection is an important co-morbidity. However, antiretroviral options for HIV/HBV co-infected children are limited and, at the time of this study, only included lamivudine. These children may remain on this regimen for many years until late adolescence. They are at high risk of developing HBV drug resistance and uncontrolled HBV disease. The aim of this study was to characterize HBV infection in HIV/HBV co-infected children. Known HIV-infected/HBsAg-positive children, previously exposed to lamivudine monotherapy against HBV, and their mothers were recruited at the Katutura Hospital paediatric HIV clinic in Windhoek, Namibia. Dried blood spot and serum samples were collected for HBV characterization and serological testing, respectively. Fifteen children and six mothers participated in the study. Eight of the 15 children (53.3%) tested HBV DNA positive; all eight children were on lamivudine-based ART. Lamivudine-associated resistance variants, together with immune escape mutants in the surface gene, were identified in all eight children. Resistance mutations included rtL80I, rtV173L, rtL180M, rtM204I/V and the overlapping sE164D, sW182*, sI195M and sW196LS variants. HBV strains belonged to genotypes E (6/8, 75%) and D3 (2/8, 25%). Further analysis of the HBV core promoter region revealed mutations associated with reduced expression of HBeAg protein and hepatocarcinogenesis. All six mothers, on HBV-active ART containing tenofovir and lamivudine, tested HBV DNA negative. This study confirms the importance of screening HIV-infected children for HBV and ensuring equity of drug access to effective HBV treatment if co-infected.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1371/journal.pone.0238839

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Role:
Author
ORCID:
0000-0002-1609-7287
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Role:
Author
ORCID:
0000-0003-2559-6034



Publisher:
Public Library of Science
Journal:
PloS One More from this journal
Volume:
15
Issue:
9
Article number:
e0238839
Publication date:
2020-09-11
Acceptance date:
2020-08-25
DOI:
EISSN:
1932-6203
Pmid:
32915862


Language:
English
Keywords:
Pubs id:
1132561
Local pid:
pubs:1132561
Deposit date:
2020-11-14
ARK identifier:

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