HBV drug resistant mutations (RAMs) identified from HBV genome sequences from Africa downloaded from the Hepatitis B Virus database (https://hbvdb.ibcp.fr/) [36] and GenBank database (http://hvdr.bioinf.wits.ac.za/alignments/) [37].

<p>HBV drug resistant mutations (RAMs) identified from HBV genome sequences from Africa downloaded from the Hepatitis B Virus database (<a href="https://hbvdb.ibcp.fr/" target="_blank">https://hbvdb.ibcp.fr/</a>) [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006629#pntd.0006629.ref036" target="_blank">36</a>] and GenBank database (<a href="http://hvdr.bioinf.wits.ac.za/alignments/" target="_blank">http://hvdr.bioinf.wits.ac.za/alignments/</a>) [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006629#pntd.0006629.ref037" target="_blank">37</a>].</p

Prevalence of HBsAg and HBeAg from 37 studies of HBV drug resistance in Africa.

<p>Prevalence of HBsAg and HBeAg from 37 studies of HBV drug resistance in Africa.</p

A systematic review of hepatitis B virus (HBV) drug and vaccine escape mutations in Africa: A call for urgent action

<div><p>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 (<a href="https://livedataoxford.shinyapps.io/1510659619-3Xkoe2NKkKJ7Drg/" target="_blank">https://livedataoxford.shinyapps.io/1510659619-3Xkoe2NKkKJ7Drg/</a>). 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.</p></div

Annotated map to summarise HBV drug resistance associated mutations (RAMs) and vaccine escape mutations (VEMs).

<p>Mutations identified from 33 studies of African cohorts published between 2007 and 2017 (inclusive). Four studies identified by our systematic literature review were not represented here as they did not report any RAMs. Full details of each citation can be found in <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006629#pntd.0006629.t001" target="_blank">Table 1</a>.</p

Prevalence of HBV resistance associated mutations (RAMs) in Pol/RT proteins among HBV infected patients in Africa.

<p>These data are derived from 27 studies of HBV drug resistance in Africa published between 2007 and 2017 (inclusive). The countries represented are listed in alphabetical order. A detailed summary of RAMs identified from each study is presented (<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006629#pntd.0006629.g002" target="_blank">Fig 2</a>, <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006629#pntd.0006629.s006" target="_blank">S4 Table</a>, <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006629#pntd.0006629.s007" target="_blank">S5 Table</a>). Prevalence of RAMs for a specific country was determined by grouping all studies from that country that reported a specific mutation. We used all individuals who tested HBsAg positive to generate a denominator in order to provide a conservative estimate of RAM prevalence, and the numerator was the total number of individuals with that specific mutation from these studies. A: treatment naïve; B: treatment experienced.</p

HBV drug resistance associated mutations (RAMs), vaccine escape mutations (VEMs) and mutations associated with Hepatitis B immunoglobulin (HBIg) resistance.

<p>HBV genes are shown in the coloured ovals. TDF = tenofovir, ETV = entecavir, 3TC = lamivudine. This figure incorporates data from eight studies; three were identified by the systematic review presented in this manuscript [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006629#pntd.0006629.ref012" target="_blank">12</a>–<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006629#pntd.0006629.ref014" target="_blank">14</a>] and five from the wider literature [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006629#pntd.0006629.ref007" target="_blank">7</a>,<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006629#pntd.0006629.ref015" target="_blank">15</a>–<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006629#pntd.0006629.ref018" target="_blank">18</a>].</p

Point-of-care screening for a current Hepatitis C virus infection: influence on uptake of a concomitant offer of HIV screening

No description supplie

Determining virological suppression and resuppression by point-of-care viral load testing in a HIV care setting in sub-Saharan Africa

Background This prospective pilot study explored same-day point-of-care viral load testing in a setting in Ghana that has yet to implement virological monitoring of antiretroviral therapy (ART). Methods Consecutive patients accessing outpatient care while on ART underwent HIV-1 RNA quantification by Xpert. Those with viraemia at the first measurement (T0) received immediate adherence counselling and were reassessed 8 weeks later (T1). Predictors of virological status were determined by logistic regression analysis. Drug resistance-associated mutations (RAMs) were detected by Sanger sequencing. Findings At T0, participants had received treatment for a median of 8·9 years; 297/333 (89·2%) were on NNRTI-based ART. The viral load was =40 copies/mL in 164/333 (49·2%) patients and =1000 copies/mL in 71/333 (21·3%). In the latter group, 50/65 (76·9%) and 55/65 (84·6%) harboured NRTI and NNRTI RAMs, respectively, and 27/65 (41·5%) had =1 tenofovir RAM. Among 150/164 (91·5%) viraemic patients that reattended at T1, 32/150 (21·3%) showed resuppression <40 copies/mL, comprising 1/65 (1·5%) subjects with T0 viral load =1000 copies/mL and 31/85 (36·5%) subjects with lower levels. A T0 viral load =1000 copies/mL and detection of RAMs predicted ongoing T1 viraemia independently of self-reported adherence levels. Among participants with T0 viral load =1000 copies/mL, 23/65 (35·4%) showed resuppression <1000 copies/mL; the response was more likely among those with higher adherence levels and no RAMs. Interpretation Same-day point-of-care viral load testing was feasible and revealed poor virological control and suboptimal resuppression rates despite adherence counselling. Controlled studies should determine optimal triaging modalities for same-day versus deferred viral load testing. Funding University of Liverpool, South Tees Infectious Diseases Research Fun

PRISMA-P (Preferred Reporting Items for Systematic review and Meta-Analysis Protocols) 2015 checklist: Recommended items to address in a systematic review protocol*.

PRISMA-P (Preferred Reporting Items for Systematic review and Meta-Analysis Protocols) 2015 checklist: Recommended items to address in a systematic review protocol*.</p

Drug resistance outcomes of long-term ART with tenofovir disoproxil fumarate in the absence of virological monitoring

Objectives: The resistance profiles of patients receiving long-term ART in sub-Saharan Africa have been poorly described. This study obtained a sensitive assessment of the resistance patterns associated with long-term tenofovir-based ART in a programmatic setting where virological monitoring is yet to become part of routine care. Methods: We studied subjects who, after a median of 4.2 years of ART, replaced zidovudine or stavudine with tenofovir disoproxil fumarate while continuing lamivudine and an NNRTI. Using deep sequencing, resistance-associated mutations (RAMs) were detected in stored samples collected at tenofovir introduction (T0) and after a median of 4.0 years (T1). Results: At T0, 19/87 (21.8%) subjects showed a detectable viral load and 8/87 (9.2%) had one or more major NNRTI RAMs, whereas 82/87 (94.3%) retained full tenofovir susceptibility. At T1, 79/87 (90.8%) subjects remained on NNRTI-based ART, 5/87 (5.7%) had introduced lopinavir/ritonavir due to immunological failure, and 3/87 (3.4%) had interrupted ART. Whilst 68/87 (78.2%) subjects maintained or achieved virological suppression between T0 and T1, a detectable viral load with NNRTI RAMs at T0 predicted lack of virological suppression at T1. Each treatment interruption, usually reflecting unavailability of the dispensary, doubled the risk of T1 viraemia. Tenofovir, lamivudine and efavirenz selected for K65R, K70E/T, L74I/V and Y115F, alongside M184V and multiple NNRTI RAMs; this resistance profile was accompanied by high viral loads and low CD4 cell counts. Conclusions: Viraemia on tenofovir, lamivudine and efavirenz led to complex resistance patterns with implications for continued drug activity and risk of onward transmission