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Title: Investigating drug and vaccine resistance as a challenge for hepatitis B virus elimination in Africa
Author: Mokaya, Jolynne
ISNI:       0000 0004 9356 7486
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2020
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Background: The United Nations Sustainable Development Goals set out to eliminate viral hepatitis by the year 2030. However, hepatitis B virus (HBV) drug resistance-associated mutations (RAMs) and/or vaccine escape mutations (VEMs) are potential barriers to the achievement of this target. I have set out to describe the prevalence, distribution and impact of RAMs and VEMs in African populations infected with HBV, with a focus on cohorts in South Africa. Methods: Through systematic literature reviews, analysis of published sequence data downloaded from GenBank, as well as sequence data generated from individuals infected with chronic HBV infection (CHB) recruited from South Africa, I have assessed the frequency, co-occurrence, distribution, evolution and transmission of HBV RAMs and VEMs. In addition, I have assessed the impact of HBV RAMs on HBV prevention of mother-to-child transmission (PMTCT) interventions through a cost-effectiveness analysis. Results: In Africa, the most common RAM was M204I/V, occurring either alone or in combination with compensatory mutations, present among HIV/HBV coinfected and HBV monoinfected patients, and identified in both reportedly treatment-naïve and treatment-experienced adults. I also report the first case from Africa with strong evidence for HBV resistance to tenofovir (TFV), on the basis of high HBV DNA viral load (VL) despite 60 months of therapy, with a suppressed HIV VL, and a combination of sequence polymorphisms that have been reported in association with TFV resistance. Although screening and treatment of all women with CHB with TFV during pregnancy may be a cost-effective strategy for HBV PMTCT in Africa, increased selection of TFV RAMs could increase health-care costs. Discussion: There is emerging evidence for polymorphisms that may reduce susceptibility to TFV. In order to drive progress towards 2030 elimination targets, there is a need for enhanced surveillance, scale-up of HBV prevention and treatment, and new therapeutic strategies that can bring about cure.
Supervisor: Matthews, Philippa ; Barnes, Eleanor Sponsor: Leverhulme Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available