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

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 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

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

Sensitivity and Specificity.

<p>Sensitivity and specificity of the different algorithms after 8, 24 and 48 weeks of therapy using a cut-off GSS of 3. The sensitivity was defined as the proportion of TCEs with a GSS of 3 or more and a virological response on all those with a virological response whereas the specificity was seen as the proportion of TCEs with a GSS less than 3 and no virological response on all those with no virological response.</p

Receiver operating Characteristic (ROC) analysis of the 24-weeks-performance of the regimen-specific genotypic susceptibility score (GSS) according to Rega 8, ANRS v2011.05 and Stanford HIVdb v6.0.11 algorithms.

<p>Receiver operating Characteristic (ROC) analysis of the 24-weeks-performance of the regimen-specific genotypic susceptibility score (GSS) according to Rega 8, ANRS v2011.05 and Stanford HIVdb v6.0.11 algorithms.</p

Distribution of the regimen-specific genotypic susceptibility scores reported by different versions of the Rega algorithm, ANRS v2011.05 and Stanford HIVdb v6.0.11.

<p>Distribution of the regimen-specific genotypic susceptibility scores reported by different versions of the Rega algorithm, ANRS v2011.05 and Stanford HIVdb v6.0.11.</p

Prevalence rates (%) of antiretroviral drugs.

<p>Nucleotide/side reverse transcriptase inhibitors (N(t)RTIs): lamivudine (3TC), tenofovir (TDF), zidovudine (AZT), emtricitabine (FTC), didanosine (DDI), abacavir (ABC), stavudine (D4T), zalcitabine (DDC); non-nucleoside reverse transcriptase inhibitors (NNRTIs): efavirenz (EFV), nevirapine (NVP), etravirine (ETR); protease inhibitors (PIs): lopinavir (LPV/r), atazanavir (ATV), nelfinavir (NFV), saquinavir (SQV), indinavir (IDV), fosamprenavir (FPV), darunavir (DRV), amprenavir (APV), tipranavir (TPV), along with boosting ritonavir (RTV).</p

Performance on the complete dataset.

<p>Overview of the performance of the different algorithms using the univariate and multivariate approach and on 8, 24 and 48 weeks of therapy. The multivariate approach includes additional variables in the model: start year of therapy, information on start of a new drug class, number of previous therapy switches, previous drug class experience, baseline viral load, baseline CD4, gender, age, risk group. Reported are the odds ratio (OR), 95% confidence interval (CI) and P-value (P) of the logistic model and the median and standard deviation (SD) of the 10-fold cross-validation area under the ROC curve (AUC).</p>*<p>The performance of the algorithms is compared with that of Rega 8 using a Wilcoxon signed-rank test and the P-value corrected for multiple testing is reported.</p