Abstract
International sustainable development goals for the elimination of viral hepatitis as a public health problem by 2030 highlight the pressing need to optimize strategies for prevention, diagnosis and treatment. Selected or transmitted resistance associated mutations (RAMs) and vaccine escape mutations (VEMs) in hepatitis B virus (HBV) may reduce the success of existing treatment and prevention strategies. These issues are particularly pertinent for many settings in Africa where there is high HBV prevalence and co-endemic HIV infection, but lack of robust epidemiological data and limited education, diagnostics and clinical care. The prevalence, distribution and impact of RAMs and VEMs in these populations are neglected in the current literature. We therefore set out to assimilate data for sub-Saharan Africa through a systematic literature review and analysis of published sequence data, and present these in an on-line database (https://livedataoxford.shinyapps.io/1510659619-3Xkoe2NKkKJ7Drg/). The majority of the data were from HIV/HBV coinfected cohorts. The commonest RAM was rtM204I/V, either alone or in combination with associated mutations, and identified in both reportedly treatment-naïve and treatment-experienced adults. We also identified the suite of mutations rtM204V/I + rtL180M + rtV173L, that has been associated with vaccine escape, in over 1/3 of cohorts. Although tenofovir has a high genetic barrier to resistance, it is of concern that emerging data suggest polymorphisms that may be associated with resistance, although the precise clinical impact of these is unknown. Overall, there is an urgent need for improved diagnostic screening, enhanced laboratory assessment of HBV before and during therapy, and sustained roll out of tenofovir in preference to lamivudine alone. Further data are needed in order to inform population and individual approaches to HBV diagnosis, monitoring and therapy in these highly vulnerable settings.
Highlights
In 2015, the World Health Organisation (WHO) estimated that 3.5% of the world’s population (257 million people) were living with Hepatitis B virus (HBV) infection, resulting in 887,000 deaths each year, mostly from complications including cirrhosis and hepatocellular carcinoma (HCC) [1]
After de-duplication, 37 articles were included. 27 articles identified from MEDLINE, SCOPUS and EMBASE were identical; five unique articles were included from EMBASE, four from SCOPUS and one from MEDLINE
WHO guidelines recommend a first-line regimen including TDF in human immunodeficiency virus (HIV)/hepatitis B virus (HBV) coinfected patients [6], and the South African Department of Health HIV/AIDS treatment guideline included TDF as first-line regimen from 2010 [71], we found a minority of studies (9/ 37, 24%) reporting TDF-containing regimens for HIV/HBV coinfected individuals
Summary
In 2015, the World Health Organisation (WHO) estimated that 3.5% of the world’s population (257 million people) were living with Hepatitis B virus (HBV) infection, resulting in 887,000 deaths each year, mostly from complications including cirrhosis and hepatocellular carcinoma (HCC) [1]. Less than 10% of the population with CHB are diagnosed, with an even smaller proportion on treatment [1,4]. This proportion is likely to be even lower in Africa. The situation in Africa is further complicated by the substantial public health challenge of coendemic human immunodeficiency virus (HIV) and HBV; coinfection worsens the prognosis in dually infected individuals [5]. There is a lack of robust epidemiological data on HBV from Africa [3,4]
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