scholarly journals Piloting a surveillance system for HIV drug resistance in the European Union

2019 ◽  
Vol 24 (19) ◽  
Author(s):  
Marita JW van de Laar ◽  
Arnold Bosman ◽  
Anastasia Pharris ◽  
Emmi Andersson ◽  
Lambert Assoumou ◽  
...  
Keyword(s):  
European Union ◽  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Surveillance System ◽  
European Economic Area ◽  
The European Union ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Hiv Drug Resistance ◽  
Case Based

Background A steady increase in HIV drug resistance (HIVDR) has been demonstrated globally in individuals initiating first-line antiretroviral therapy (ART). To support effective use of ART and prevent spread of HIVDR, monitoring is essential. Aim We piloted a surveillance system for transmitted HIVDR to assess the feasibility of implementation at the European level. Method All 31 countries in the European Union and European Economic Area were invited to retrospectively submit data on individuals newly diagnosed with HIV in 2015 who were tested for antiviral susceptibility before ART, either as case-based or as aggregate data. We used the Stanford HIV database algorithm to translate genetic sequences into levels of drug resistance. Results Nine countries participated, with six reporting case-based data on 1,680 individuals and four reporting aggregated data on 1,402 cases. Sequence data were available for 1,417 cases: 14.5% of individuals (n = 244) showed resistance to at least one antiretroviral drug. In case-based surveillance, the highest levels of transmitted HIVDR were observed for non-nucleoside reverse-transcriptase inhibitors (NNRTIs) with resistance detected in 8.6% (n = 145), followed by resistance to nucleoside reverse-transcriptase inhibitors (NRTI) (5.1%; n = 85) and protease inhibitors (2.0%; n = 34). Conclusion We conclude that standard reporting of HIVDR data was feasible in the participating countries. Legal barriers for data sharing, consensus on definitions and standardisation of interpretation algorithms should be clarified in the process of enhancing European-wide HIV surveillance with drug resistance information.

scholarly journals Barcoding analysis of HIV drug resistance mutations using Oxford Nanopore MinION (ONT) sequencing

2017 ◽  
Author(s):  
Claudia Gonzalez ◽  
Jessica Gondola ◽  
Alma Y Ortiz ◽  
Juan M Castillo ◽  
Juan M Pascale ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Treatment Resistance ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Hiv Drug Resistance ◽  
Drug Resistance Mutations ◽  
Oxford Nanopore ◽  
Pre Treatment

ABSTRACTDetermination of HIV drug resistance (HIVDR) is becoming an integral baseline HIV evaluation for newly infected subjects, as the level of pre-treatment resistance is increasing worldwide. Until now, the gold standard for monitoring ART mutations is the Sanger sequencing method, however, next-generation sequencing technologies (NGS) because high-throughput capability, are gaining attention as a method for detection of HIVDR. In the present work, we evaluated the use of the Oxford Nanopore Technologies (ONT) MinION as an alternative method for detection of drug resistance mutations in pre-treatment HIV positive subjects.We evaluate 36 samples taken during November 2016 from treatment naïve subjects with age greater than 18 years old, who went to the lab for their first HIV monitoring. To evaluate the agreement between Sanger and MinION generated sequences, we aligned the sequences (∼1200bp) with muscle v. 3.8.31. Then we counted the differences and calculated the p-distance of the obtained sequences, comparing paired sequences and grouping Sanger and MinION obtained sequences. The percentage of similarity among each sequence was also evaluated.All samples were submitted to the Standford University HIV drug resistance database (HIVdb version 8.4). Then we compared the resistance predictions obtained from the sequences generated by Sanger and MinION methods.Results: The median of available pores was 1314 for the first run, 1215 for the second run, and 536 for the third run. After 3 hours with SQK-NSK007 a total of 18803 2D reads were base-called and in 16577 reads (88%) a barcode was detected.Comparing the nucleotide differences of each sample, we observed that 23 (74%) samples had identical sequence, for the other samples the percentage of identity among each analyzed sequence was greater than 95%. A good positive predictive value (100%) in the estimation of drug resistance mutations in the groups of protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTIs), and non-nucleoside reverse transcriptase inhibitors (NNRTIs).We present an approach for the analysis of HIV reads generated with MinION ONT, further studies are guaranteed before the application of this methodology in clinical settings to assess its suitability for HIVDR testing.

scholarly journals Prevalence and Correlates of Pre-Treatment HIV Drug Resistance among HIV-Infected Children in Ethiopia

Viruses ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 877 ◽  
Author(s):  
Birkneh Tilahun Tadesse ◽  
Olivia Tsai ◽  
Adugna Chala ◽  
Tolossa Eticha Chaka ◽  
Temesgen Eromo ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Hiv Treatment ◽  
Hiv Care ◽  
Virologic Suppression ◽  
Reverse Transcriptase Inhibitors ◽  
Resource Limited Settings ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Hiv Drug Resistance ◽  
Resource Limited

Pediatric human immunodeficiency virus (HIV) care in resource-limited settings remains a major challenge to achieving global HIV treatment and virologic suppression targets, in part because the administration of combination antiretroviral therapies (cART) is inherently complex in this population and because viral load and drug resistance genotyping are not routinely available in these settings. Children may also be at elevated risk of transmission of drug-resistant HIV as a result of suboptimal antiretroviral administration for prevention of mother-to-child transmission. We investigated the prevalence and the correlates of pretreatment HIV drug resistance (PDR) among HIV-infected, cART-naive children in Ethiopia. We observed an overall PDR rate of 14%, where all cases featured resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs): ~9% of participants harbored resistance solely to NNRTIs while ~5% harbored resistance to both NNRTIs and nucleoside reverse transcriptase inhibitors (NRTIs). No resistance to protease inhibitors was observed. No sociodemographic or clinical parameters were significantly associated with PDR, though limited statistical power is noted. The relatively high (14%) rate of NNRTI resistance in cART-naive children supports the use of non-NNRTI-based regimens in first-line pediatric treatment in Ethiopia and underscores the urgent need for access to additional antiretroviral classes in resource-limited settings.

Evaluation of a novel in-house HIV-1 genotype drug resistance assay using clinical samples in China

2021 ◽  
Vol 19 ◽  
Author(s):  
Peijie Gao ◽  
Fengting Yu ◽  
Xiaozhen Yang ◽  
Dan Li ◽  
Yalun Shi ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
High Efficiency ◽  
Clinical Samples ◽  
Genotype Distribution ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Subtype B ◽  
Hiv 1

Background: HIV drug resistance poses a major challenge for anti-retroviral treatment (ART) and the prevention and control of HIV epidemic. Objective: The study aims to establish a novel in-house assay with high efficiency, named AP in-house method, that would be suitable for HIV-1 drug resistance detection in China. Methods: An in-house HIV-1 genotyping method was used to sequence the partial pol gene from 60 clinical plasma samples; the results of our test were compared with a commercial ViroSeq HIV-1 genotyping system. Results : Among sixty samples, 58(96.7%) were successfully amplified by AP in-house method, five of them harbored viral load below 1,000 copies/ml. The genotype distribution was 43.1% CRF07_BC (25/58), 39.7% CRF01_AE (23/58), 6.9% CRF55_01B (4/58), 5.2% subtype B (3/58) and 5.2% CRF08_BC (3/58). Compared with that of the ViroSeq system, the consistent rate of these nucleotides and amino acids obtained by AP in-house method was up to 99.5 ± 0.4% and 99.5 ± 0.4%, respectively. A total of 290 HIV-1 drug resistance mutations were identified by two methods, including 126 nucleoside reverse transcriptase inhibitors (NRTIs), 145 non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 19 protease inhibitors (PIs) resistance mutations. Out of them, 94.1% (273/290) were completely concordant between the AP in-house method and the ViroSeq system. Conclusion: Overall, the evaluation of AP in-house method provided comparable results to those of the ViroSeq system on diversified HIV-1 subtypes in China.

scholarly journals Drug resistance among tuberculosis cases in the European Union and European Economic Area, 2007 to 2012

2014 ◽  
Vol 19 (10) ◽  
Author(s):  
M J van der Werf ◽  
C Ködmön ◽  
V Hollo ◽  
A Sandgren ◽  
P Zucs
Keyword(s):  
European Union ◽  
Drug Resistance ◽  
European Economic Area ◽  
The European Union ◽  
European Economic ◽  
Binary File ◽  
Economic Area

Binary file ES_Abstracts_Final_ECDC.txt matches

scholarly journals Dynamics and drivers of HIV-1 drug resistance to non-nucleoside reverse-transcriptase inhibitors in nine African countries

2020 ◽  
Author(s):  
Julien Riou ◽  
Carole Dupont ◽  
Silvia Bertagnolio ◽  
Ravindra Gupta ◽  
Roger D Kouyos ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Survey Data ◽  
Southern Africa ◽  
Hiv Care ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Nnrti Resistance ◽  
Country Level ◽  
Hiv 1

Background. The rise of HIV-1 drug resistance to non-nucleoside reverse-transcriptase inhibitors (NNRTI) is a major problem in countries of southern Africa. Understanding the dynamics and drivers of NNRTI resistance at the country level is of critical importance for planning future antiretroviral therapy (ART) programs. Methods. We collected survey data on pretreatment drug resistance (PDR) to NNRTIs in nine countries of southern Africa from 2000 to 2018. We fitted a dynamic transmission model to key indicators of the local HIV-1 epidemics (HIV-1 prevalence, ART coverage and mortality) and to survey data about NNRTI PDR using a Bayesian hierarchical framework. We estimated two country-level indicators: the proportion of NNRTI PDR that cannot be attributed to ART programmes and the vulnerability to NNRTI PDR within ART programmes. We explored associations between vulnerability to NNRTI PDR and country-level covariates.Findings. The model reliably described the dynamics of HIV-1 and the dynamics of NNRTI PDR in each country. Predicted levels of NNRTI PDR in 2018 ranged between 3.3% (95% credible interval 1.9% to 7.1%) in Mozambique and 25.3% (17.9% to 33.8%) in Eswatini. The main determinant of high NNRTI PDR were the conjunction of high ART coverage and high vulnerability to NNRTI PDR within ART programmes. Heterogeneity in the vulnerability to NNRTI resistance was associated with features of the healthcare financing system at the national level.Interpretation. Between-country comparison shows that NNRTI PDR can be controlled despite high levels of ART coverage, as in Botswana, Lesotho, Mozambique and Zambia, likely because of better adherence, patient management procedures and quality in HIV care service delivery.

scholarly journals Transmitted drug resistance and transmission clusters among HIV-1 treatment-naïve patients in Guangdong, China: a cross-sectional study

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Yun Lan ◽  
Linghua Li ◽  
Xiang He ◽  
Fengyu Hu ◽  
Xizi Deng ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Transmitted Drug Resistance ◽  
Resistance Mutations ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Cross Sectional ◽  
Genetic Transmission ◽  
Treatment Naïve ◽  
Hiv 1

Abstract Background Transmitted drug resistance (TDR) that affects the effectiveness of the first-line antiretroviral therapy (ART) regimen is becoming prevalent worldwide. However, its prevalence and transmission among HIV-1 treatment-naïve patients in Guangdong, China are rarely reported. We aimed to comprehensively analyze the prevalence of TDR and the transmission clusters of HIV-1 infected persons before ART in Guangdong. Methods The HIV-1 treatment-naïve patients were recruited between January 2018 and December 2018. The HIV-1 pol region was amplified by reverse transcriptional PCR and sequenced by sanger sequencing. Genotypes, surveillance drug resistance mutations (SDRMs) and TDR were analyzed. Genetic transmission clusters among patients were identified by pairwise Tamura-Nei 93 genetic distance, with a threshold of 0.015. Results A total of 2368 (97.17%) HIV-1 pol sequences were successfully amplified and sequenced from the enrolled 2437 patients. CRF07_BC (35.90%, 850/2368), CRF01_AE (35.56%, 842/2368) and CRF55_01B (10.30%, 244/2368) were the main HIV-1 genotypes circulating in Guangdong. Twenty-one SDRMs were identified among fifty-two drug-resistant sequences. The overall prevalence of TDR was 2.20% (52/2368). Among the 2368 patients who underwent sequencing, 8 (0.34%) had TDR to protease inhibitors (PIs), 22 (0.93%) to nucleoside reverse transcriptase inhibitors (NRTIs), and 23 (0.97%) to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Two (0.08%) sequences showed dual-class resistance to both NRTIs and NNRTIs, and no sequences showed triple-class resistance. A total of 1066 (45.02%) sequences were segregated into 194 clusters, ranging from 2 to 414 sequences. In total, 15 (28.85%) of patients with TDR were included in 9 clusters; one cluster contained two TDR sequences with the K103N mutation was observed. Conclusions There is high HIV-1 genetic heterogeneity among patients in Guangdong. Although the overall prevalence of TDR is low, it is still necessary to remain vigilant regarding some important SDRMs.

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