scholarly journals RETRACTED: A low-cost in-house HIV integrase strand transfer inhibitor drug resistance test for resource-limited settings [version 1; peer review: awaiting peer review]

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 306
Author(s):  
Vera M. Onwong'a ◽  
Rachael W. Gachogo ◽  
Moses M. Masika ◽  
Graeme B. Jacobs ◽  
Frank G. Onyambu
Keyword(s):  
Drug Resistance ◽  
Peer Review ◽  
Low Cost ◽  
Strand Transfer ◽  
Hiv Integrase ◽  
Resource Limited Settings ◽  
Resource Limited ◽  
Transfer Inhibitor ◽  
Inhibitor Drug ◽  
Integrase Strand Transfer Inhibitor

At the request of the authors, the article titled 'A low-cost in-house HIV integrase strand transfer inhibitor drug resistance test for resource-limited settings' ([version 1; peer review: awaiting peer review]. F1000Research 2021, 10:260, https://doi.org/10.12688/f1000research.28404.1) has been retracted from F1000Research. Since publication, it has come to the attention of the authors that the primers described in Table 1 were incorrect. As this article contains information which should not be publicly available the content of the article has been removed.  The authors apologise for this honest error, and intend to republish the article with the correct primer information. Unfortunately, Dr Graeme B. Jacobs has passed away since publication of version 1 of this article.

scholarly journals A low-cost in-house HIV integrase strand transfer inhibitor drug resistance test for resource-limited settings

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 260
Author(s):  
Vera M. Onwong'a ◽  
Rachael W. Gachogo ◽  
Moses M. Masika ◽  
Graeme B. Jacobs ◽  
Frank G. Onyambu
Keyword(s):  
Drug Resistance ◽  
Clinical Sample ◽  
Patient Treatment ◽  
Resistance Testing ◽  
People Living With Hiv ◽  
Strand Transfer ◽  
Hiv Integrase ◽  
Resource Limited Settings ◽  
Resource Limited ◽  
Hiv 1

Background: HIV-1 drug resistance testing (DRT) is vital for monitoring of individual patient treatment outcomes and for public health surveillance. Access to HIV-1 DRT is limited in resource-poor settings, including Kenya due to its costly nature. Recent inclusion of integrase strand transfer inhibitors (INSTIs) in first-line treatment for all people living with HIV-1 (PLHIV-1) underscores the need for an INSTI DRT. This study aims to validate a cost-effective in-house DRT method to detect HIV-1 Integrase resistance-associated mutations (RAMs) using HIV positive plasma derived samples Methods: Thirty-six plasma derived samples were used to assess the performance characteristics including accuracy, precision, reproducibility and amplification sensitivity of an in-house method in comparison with a reference assay. Cost estimation per test followed an incremental ingredient costing approach. Clinical application of the in-house test was evaluated on a plasma sample from a patient failing an INSTI-based regimen. Results: Comparison of the in-house and reference assay gave mean nucleotide and amino acid sequence identity of 99.49 %, CI [99.21- 99.77] and 99%, CI [98.58, 99.42] respectively. Complete concordance was observed by both assays in detection of the T97TA INSTI RAM. Precision and reproducibility assessment revealed mean nucleotide sequence identities of 100% and 99.14% respectively. The amplification sensitivity was 100% for samples with VL> 1000 copies/mL (n=8) and 50% for samples with VL<1000 copies/mL. Two major (G118R and E188K) and two accessory INSTI mutations (G149A and E157Q) were detected from the clinical sample of a patient failing an INSTI-based therapy. Cost analysis estimated the cost per test at $50.31. Conclusion: The developed HIV-Integrase assay met the validation acceptance criteria and demonstrates the ability to detect clinically relevant INSTI-resistance-associated mutations, highlighting its potential use as an alternative to commercial INSTI tests in resource-limited settings.

Progressive emergence of an S153F plus R263K combination of integrase mutations in the proviral DNA of one individual successfully treated with dolutegravir

2020 ◽  
Author(s):  
Hanh T Pham ◽  
Brunna M Alves ◽  
Sunbin Yoo ◽  
Meng A Xiao ◽  
Jing Leng ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Dna Binding ◽  
Drug Resistant ◽  
Strand Transfer ◽  
Viral Genomes ◽  
Proviral Dna ◽  
Viral Loads ◽  
Subtype B ◽  
Transfer Inhibitor ◽  
Integrase Strand Transfer Inhibitor

Abstract Objectives The development of HIV drug resistance against the integrase strand transfer inhibitor dolutegravir is rare. We report here the transient detection, by near full-genome ultradeep sequencing, of minority HIV-1 subtype B variants bearing the S153F and R263K integrase substitutions in the proviral DNA from blood cells of one patient who successfully initiated dolutegravir-based ART, over 24 weeks. Our objective was to study the effects of these substitutions. Methods Strand transfer and DNA-binding activities of recombinant integrase proteins were measured in cell-free assays. Cell-based resistance, infectivity and replicative capacities were measured using molecular clones. Structural modelling was performed to understand experimental results. Results R263K emerged first, followed by the addition of S153F at Week 12. By Week 24, both mutations remained present, but at lower prevalence. We confirmed the coexistence of S153F and R263K on single viral genomes. Combining S153F or S153Y with R263K decreased integration and viral replicative capacity and conferred high levels of drug resistance against all integrase inhibitors. Alone, S153Y and S153F did little to infectivity or dolutegravir resistance. We identified altered DNA binding as a mechanism of resistance. The patient remained with undetectable viral loads at all timepoints. Conclusions Drug-resistant minority variants have often been reported under suppressive ART. Our study adds to these observations by unravelling a progression towards higher levels of resistance through a novel pathway despite continuous undetectable viral loads. Poorly replicative HIV drug-resistant minority proviral variants did not compromise viral suppression in one individual treated with dolutegravir.

scholarly journals Optimization of a Low Cost and Broadly Sensitive Genotyping Assay for HIV-1 Drug Resistance Surveillance and Monitoring in Resource-Limited Settings

PLoS ONE ◽  
2011 ◽  
Vol 6 (11) ◽  
pp. e28184 ◽  
Author(s):  
Zhiyong Zhou ◽  
Nick Wagar ◽  
Joshua R. DeVos ◽  
Erin Rottinghaus ◽  
Karidia Diallo ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Low Cost ◽  
Resource Limited Settings ◽  
Genotyping Assay ◽  
Resource Limited ◽  
Hiv 1

Dolutegravir as a trigger for DRESS syndrome?

2018 ◽  
Vol 29 (10) ◽  
pp. 1036-1038 ◽  
Author(s):  
Charlotte Martin ◽  
Marie-Christine Payen ◽  
Stephane De Wit
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Reaction ◽  
Second Generation ◽  
Strand Transfer ◽  
Dress Syndrome ◽  
Immunodeficiency Virus ◽  
Transfer Inhibitor ◽  
Inhibitor Drug ◽  
Systemic Symptoms ◽  
Integrase Strand Transfer Inhibitor

Dolutegravir is an increasingly-used second-generation human immunodeficiency virus integrase strand transfer inhibitor. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome has been described in several patients treated with raltegravir but to our knowledge, there is no previous report of DRESS syndrome associated with dolutegravir.

Emergent drug resistance with integrase strand transfer inhibitor-based regimens

AIDS ◽  
2017 ◽  
Vol 31 (10) ◽  
pp. 1425-1434 ◽  
Author(s):  
Katherine J. Lepik ◽  
P. Richard Harrigan ◽  
Benita Yip ◽  
Lu Wang ◽  
Marjorie A. Robbins ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Strand Transfer ◽  
Transfer Inhibitor ◽  
Integrase Strand Transfer Inhibitor

scholarly journals Prevalence of Human Immunodeficiency Virus-1 Integrase Strand Transfer Inhibitor Resistance in British Columbia, Canada Between 2009 and 2016: A Longitudinal Analysis

2019 ◽  
Vol 6 (3) ◽  
Author(s):  
Kimia Kamelian ◽  
Katherine J Lepik ◽  
William Chau ◽  
Benita Yip ◽  
Wendy W Zhang ◽  
...  
Keyword(s):  
British Columbia ◽  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Strand Transfer ◽  
Resistance Mutations ◽  
Immunodeficiency Virus ◽  
Transfer Inhibitor ◽  
Inhibitor Resistance ◽  
Integrase Strand Transfer Inhibitor ◽  
Human Immunodeficiency Virus 1

AbstractBackgroundIntegrase strand transfer inhibitors (INSTIs) are highly efficacious and well tolerated antiretrovirals with fewer adverse side-effects relative to other classes of antiretrovirals. The use of INSTIs raltegravir, elvitegravir, and dolutegravir has increased dramatically over recent years. However, there is limited information about the evolution and prevalence of INSTI resistance mutations in clinical human immunodeficiency virus populations.MethodsHuman immunodeficiency virus-1-positive individuals ≥19 years were included if they received ≥1 dispensed prescription of antiretroviral therapy (ART) in British Columbia between 2009 and 2016 (N = 9358). Physician-ordered drug resistance tests were analyzed and protease inhibitor (PI), reverse-transcriptase inhibitor (RT), and INSTI resistance were defined as having ≥1 sample with a combined, cumulative score ≥30 by Stanford HIV Drug Resistance Algorithm version 7.0.1.ResultsAlthough most ART-treated individuals were tested for PI and RT resistance, INSTI resistance testing lagged behind the uptake of INSTIs among INSTI-treated individuals (11% in 2009; 34% in 2016). The prevalence of INSTI resistance was relatively low, but it increased from 1 to 7 per 1000 ART-treated individuals between 2009 and 2016 (P &lt; .0001, R2 = 0.98). Integrase strand transfer inhibitor resistance mutations increased at integrase codons 66, 97, 140, 148, 155, and 263.ConclusionsThe prevalence of INSTI resistance remains low compared with PI and RT resistance in ART-treated populations but is expanding with increased INSTI use.

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