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3. Effective, Practical PON Monitoring Beyond the Splitter

Author

Parkin, Neil, Minoughan, Sophie, and Iqbal, Md Asif

Subjects
Electrical Engineering and Systems Science - Signal Processing
Abstract

Monitoring beyond the splitter in a PON is costly due to the need for additional hardware. A non-standard monitoring wavelength can reduce cost and increase the visibility of customers to 97% on a C+ GPON

Published
2022

5. An investigation into the influence of trust on the sharing of practical knowledge in technology producing small to medium enterprises (SMEs)

Author

Parkin, Neil, Penlington, Roge, and Connor, Chris

Subjects
658.02, H900 Others in Engineering, N100 Business studies
Abstract

This study that uses ethnographic research methods explores how trust influences the sharing of practical knowledge in technology producing SMEs. More specifically, this project investigates how trust behaviours influence the sharing of various types of tacit and explicit practical knowledge. Currently, practice theory research recommends how practical knowledge can be shared however, efforts to share practical knowledge generally fail due to trust not been developed adequately in the collaborative relationships formed by companies. This research aims to inform practice theory of how SMEs can develop collaborative relationships more effectively. To succeed, these companies are particularly dependent on collaborative working as a source for growth and competitive advantage. This investigation uses a qualitative research methodology, which employs a multiple case study approach where semi-structured interviews have been conducted with six engineers, three of whom work in large companies and three in SMEs. Observations were also conducted for one case study. These participants work at various levels and the companies themselves are based in a variety of geographic locations across the UK. Based on the use of a thematic analysis on the interview data it was possible to characterise a practical knowledge sharing culture. In addition, the research outlines the specific perceptions and experiences of participants who adopted trust based strategies for sharing practical knowledge over the life of a project. By applying a method devised in this research called narrative mapping, it was possible to identify patterns between trust behaviours and types of practical knowledge shared from participants' anecdotes. As the interviewees' anecdotes relate to specific relationship phases over a project life cycle, the research was able to build up a picture of how trust develops over the life stages of a project. The findings provide a novel way of helping SMEs to develop effective collaborative relationships and associated working practices and inform future trust and practice theory research.

Published
2020

8. Performance comparison of the Maxim and Sedia Limiting Antigen Avidity assays for HIV incidence surveillance

Author

Sempa, Joseph B, Welte, Alex, Busch, Michael P, Hall, Jake, Hampton, Dylan, Facente, Shelley N, Keating, Sheila M, Marson, Kara, Parkin, Neil, Pilcher, Christopher D, Murphy, Gary, Grebe, Eduard, and Assays, on behalf of the Consortium for the Evaluation and Performance of HIV Incidence

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Clinical Sciences, Infectious Diseases, HIV/AIDS, Sexually Transmitted Infections, Infection, Good Health and Well Being, Algorithms, Cross-Sectional Studies, Epidemics, Female, HIV Antigens, HIV Infections, HIV-1, Humans, Incidence, Kenya, Population Surveillance, Viral Load, Consortium for the Evaluation and Performance of HIV Incidence Assays, General Science & Technology
Abstract

BackgroundTwo manufacturers, Maxim Biomedical and Sedia Biosciences Corporation, supply CDC-approved versions of the HIV-1 Limiting Antigen Avidity EIA (LAg) for detecting 'recent' HIV infection in cross-sectional incidence estimation. This study assesses and compares the performance of the two assays for incidence surveillance.MethodsWe ran both assays on a panel of 2,500 well-characterized HIV-1-infected specimens. We analysed concordance of assay results, assessed reproducibility using repeat testing and estimated mean durations of recent infection (MDRIs) and false-recent rates (FRRs) for a range of normalized optical density (ODn) thresholds, alone and in combination with viral load thresholds. We defined three hypothetical surveillance scenarios, similar to the Kenyan and South African epidemics, and a concentrated epidemic. These scenarios allowed us to evaluate the precision of incidence estimates obtained by means of various recent infection testing algorithms (RITAs) based on each of the two assays.ResultsThe Maxim assay produced lower ODn values than the Sedia assay on average, largely as a result of higher calibrator readings (mean OD of 0.749 vs. 0.643), with correlation of normalized readings lower (R2 = 0.908 vs. R2 = 0.938). Reproducibility on blinded control specimens was slightly better for Maxim. The MDRI of a Maxim-based algorithm at the 'standard' threshold (ODn ≤1.5 & VL >1,000) was 201 days (95% CI: 180,223) and for Sedia 171 (152,191). The difference Differences in MDRI were estimated at 32.7 (22.9,42.8) and 30.9 days (21.7,40.7) for the two algorithms, respectively. Commensurately, the Maxim algorithm had a higher FRR in treatment-naive subjects (1.7% vs. 1.1%). The two assays produced similar precision of incidence estimates in the three surveillance scenarios.ConclusionsDifferences between the assays can be primarily attributed to the calibrators supplied by the manufacturers. Performance for surveillance was extremely similar, although different thresholds were optimal (i.e. produced the lowest variance of incidence estimates) and at any given ODn threshold, different estimates of MDRI and FRR were obtained. The two assays cannot be treated as interchangeable: assay and algorithm-specific performance characteristic estimates must be used for survey planning and incidence estimation.

Published
2019

9. Computational analysis of antibody dynamics identifies recent HIV-1 infection

Author

Seaton, Kelly E, Vandergrift, Nathan A, Deal, Aaron W, Rountree, Wes, Bainbridge, John, Grebe, Eduard, Anderson, David A, Sawant, Sheetal, Shen, Xiaoying, Yates, Nicole L, Denny, Thomas N, Liao, Hua-Xin, Haynes, Barton F, Robb, Merlin L, Parkin, Neil, Santos, Breno R, Garrett, Nigel, Price, Matthew A, Naniche, Denise, Duerr, Ann C, Keating, Sheila, Hampton, Dylan, Facente, Shelley, Marson, Kara, Welte, Alex, Pilcher, Christopher D, Cohen, Myron S, and Tomaras, Georgia D

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, HIV/AIDS, Sexually Transmitted Infections, Vaccine Related, Biotechnology, Infectious Diseases, Vaccine Related (AIDS), Prevention, Immunization, Infection, Good Health and Well Being, Antibody Affinity, Antigen-Antibody Reactions, Biomarkers, Computational Biology, HIV Antibodies, HIV Antigens, HIV Infections, HIV-1, Humans, Immunoglobulin G, Incidence, Retrospective Studies, Time Factors, CEPHIA group, AIDS/HIV, Antigen, Immunoglobulins, Biomedical and clinical sciences, Health sciences
Abstract

Accurate HIV-1 incidence estimation is critical to the success of HIV-1 prevention strategies. Current assays are limited by high false recent rates (FRRs) in certain populations and a short mean duration of recent infection (MDRI). Dynamic early HIV-1 antibody response kinetics were harnessed to identify biomarkers for improved incidence assays. We conducted retrospective analyses on circulating antibodies from known recent and longstanding infections and evaluated binding and avidity measurements of Env and non-Env antigens and multiple antibody forms (i.e., IgG, IgA, IgG3, IgG4, dIgA, and IgM) in a diverse panel of 164 HIV-1-infected participants (clades A, B, C). Discriminant function analysis identified an optimal set of measurements that were subsequently evaluated in a 324-specimen blinded biomarker validation panel. These biomarkers included clade C gp140 IgG3, transmitted/founder clade C gp140 IgG4 avidity, clade B gp140 IgG4 avidity, and gp41 immunodominant region IgG avidity. MDRI was estimated at 215 day or alternatively, 267 days. FRRs in untreated and treated subjects were 5.0% and 3.6%, respectively. Thus, computational analysis of dynamic HIV-1 antibody isotype and antigen interactions during infection enabled design of a promising HIV-1 recency assay for improved cross-sectional incidence estimation.

Published
2017

10. Global and regional epidemiology of HIV-1 recombinants in 1990–2015: a systematic review and global survey

Author

Abimiku, Alash'le G, Agwale, Simon, Archibald, Chris, Avidor, Boaz, Barbás, María Gabriela, Barre-Sinoussi, Francoise, Barugahare, Banson, Belabbes, El Hadj, Bertagnolio, Silvia, Birx, Deborah, Bobkov, Aleksei F, Brandful, James, Bredell, Helba, Brennan, Catherine A, Brooks, James, Bruckova, Marie, Buonaguro, Luigi, Buonaguro, Franco, Buttò, Stefano, Buvé, Anne, Campbell, Mary, Carr, Jean, Carrera, Alex, Carrillo, Manuel Gómez, Celum, Connie, Chaplin, Beth, Charles, Macarthur, Chatzidimitriou, Dimitrios, Chen, Zhiwei, Chijiwa, Katsumi, Cooper, David, Cunningham, Philip, Dagnra, Anoumou, de Gascun, Cillian F, Del Amo, Julia, Delgado, Elena, Dietrich, Ursula, Dwyer, Dominic, Ellenberger, Dennis, Ensoli, Barbara, Essex, Max, Gao, Feng, Fleury, Hervé, Fonjungo, Peter N, Foulongne, Vincent, Gadkari, Deepak A, García, Federico, Garsia, Roger, Gershy-Damet, Guy Michel, Glynn, Judith R, Goodall, Ruth, Grossman, Zehava, Lindenmeyer-Guimarães, Monick, Hahn, Beatrice, Hamers, Raph L, Hamouda, Osamah, Handema, Ray, He, Xiang, Herbeck, Joshua, Ho, David D, Holguin, Africa, Hosseinipour, Mina, Hunt, Gillian, Ito, Masahiko, Bel Hadj Kacem, Mohamed Ali, Kahle, Erin, Kaleebu, Pontiano, Kalish, Marcia, Kamarulzaman, Adeeba, Kang, Chun, Kanki, Phyllis, Karamov, Edward, Karasi, Jean-Claude, Kayitenkore, Kayitesi, Kelleher, Tony, Kitayaporn, Dwip, Kostrikis, Leondios G, Kucherer, Claudia, Lara, Claudia, Leitner, Thomas, Liitsola, Kirsi, Lingappa, Jai, Linka, Marek, Lorenzana de Rivera, Ivette, Lukashov, Vladimir, Maayan, Shlomo, Mayr, Luzia, McCutchan, Francine, Meda, Nicolas, Menu, Elisabeth, Mhalu, Fred, Mloka, Doreen, Mokili, John L, Montes, Brigitte, Mor, Orna, Morgado, Mariza, Mosha, Fausta, Moussi, Awatef, Mullins, James, Najera, Rafael, Nasr, Mejda, Ndembi, Nicaise, Neilson, Joel R, Nerurkar, Vivek R, Neuhann, Florian, Nolte, Claudine, Novitsky, Vlad, Nyambi, Philippe, Ofner, Marianna, Paladin, Fem J, Papa, Anna, Pape, Jean, Parkin, Neil, Parry, Chris, Peeters, Martine, Pelletier, Alexandra, Pérez-Álvarez, Lucía, Pillay, Deenan, Pinto, Angie, Quang, Trinh Duy, Rademeyer, Cecilia, Raikanikoda, Filimone, Rayfield, Mark A, Reynes, Jean-Marc, Rinke de Wit, Tobias, Robbins, Kenneth E, Rolland, Morgane, Rousseau, Christine, Salazar-Gonzales, Jesus, Salem, Hanan, Salminen, Mika, Salomon, Horacio, Sandstrom, Paul, Santiago, Mario L, Sarr, Abdoulaye D, Schroeder, Bryan, Segondy, Michel, Selhorst, Philippe, Sempala, Sylvester, Servais, Jean, Shaik, Ansari, Shao, Yiming, Slim, Amine, Soares, Marcelo A, Songok, Elijah, Stewart, Debbie, Stokes, Julie, Subbarao, Shambavi, Sutthent, Ruengpung, Takehisa, Jun, Tanuri, Amilcar, Tee, Kok Keng, Thapa, Kiran, Thomson, Michael, Tran, Tyna, Urassa, Willy, Ushijima, Hiroshi, van de Perre, Philippe, van der Groen, Guido, van Laethem, Kristel, van Oosterhout, Joep, van Sighem, Ard, van Wijngaerden, Eric, Vandamme, Anne-Mieke, Vercauteren, Jurgen, Vidal, Nicole, Wallace, Lesley, Williamson, Carolyn, Wolday, Dawit, Xu, Jianqing, Yang, Chunfu, Zhang, Linqi, Zhang, Rong, Hemelaar, Joris, Elangovan, Ramyiadarsini, Yun, Jason, Dickson-Tetteh, Leslie, Kirtley, Shona, Gouws-Williams, Eleanor, and Ghys, Peter D

Published
2020
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11. Global and regional molecular epidemiology of HIV-1, 1990–2015: a systematic review, global survey, and trend analysis

Author

Abimiku, Alash'le G, Agwale, Simon, Archibald, Chris, Avidor, Boaz, Barbás, María Gabriela, Barre-Sinoussi, Francoise, Barugahare, Banson, Belabbes, El Hadj, Bertagnolio, Silvia, Birx, Deborah, Bobkov, Aleksei F, Brandful, James, Bredell, Helba, Brennan, Catherine A, Brooks, James, Bruckova, Marie, Buonaguro, Luigi, Buonaguro, Franco, Buttò, Stefano, Buve, Anne, Campbell, Mary, Carr, Jean, Carrera, Alex, Carrillo, Manuel Gómez, Celum, Connie, Chaplin, Beth, Charles, Macarthur, Chatzidimitriou, Dimitrios, Chen, Zhiwei, Chijiwa, Katsumi, Cooper, David, Cunningham, Philip, Dagnra, Anoumou, de Gascun, Cillian F, Del Amo, Julia, Delgado, Elena, Dietrich, Ursula, Dwyer, Dominic, Ellenberger, Dennis, Ensoli, Barbara, Essex, Max, Gao, Feng, Fleury, Herve, Fonjungo, Peter N, Foulongne, Vincent, Gadkari, Deepak A, García, Federico, Garsia, Roger, Gershy-Damet, Guy Michel, Glynn, Judith R, Goodall, Ruth, Grossman, Zehava, Lindenmeyer-Guimarães, Monick, Hahn, Beatrice, Hamers, Raph L, Hamouda, Osamah, Handema, Ray, He, Xiang, Herbeck, Joshua, Ho, David D, Holguin, Africa, Hosseinipour, Mina, Hunt, Gillian, Ito, Masahiko, Bel Hadj Kacem, Mohamed Ali, Kahle, Erin, Kaleebu, Pontiano Kaleebu, Kalish, Marcia, Kamarulzaman, Adeeba, Kang, Chun, Kanki, Phyllis, Karamov, Edward, Karasi, Jean-Claude, Kayitenkore, Kayitesi, Kelleher, Tony, Kitayaporn, Dwip, Kostrikis, Leondios G, Kucherer, Claudia, Lara, Claudia, Leitner, Thomas, Liitsola, Kirsi, Lingappa, Jai, Linka, Marek, Lorenzana de Rivera, Ivette, Lukashov, Vladimir, Maayan, Shlomo, Mayr, Luzia, McCutchan, Francine, Meda, Nicolas, Menu, Elisabeth, Mhalu, Fred, Mloka, Doreen, Mokili, John L, Montes, Brigitte, Mor, Orna, Morgado, Mariza, Mosha, Fausta, Moussi, Awatef, Mullins, James, Najera, Rafael, Nasr, Mejda, Ndembi, Nicaise, Neilson, Joel R, Nerurkar, Vivek R, Neuhann, Florian, Nolte, Claudine, Novitsky, Vlad, Nyambi, Philippe, Ofner, Marianna, Paladin, Fem J, Papa, Anna, Pape, Jean, Parkin, Neil, Parry, Chris, Peeters, Martine, Pelletier, Alexandra, Pérez-Álvarez, Lucía, Pillay, Deenan, Pinto, Angie, Quang, Trinh Duy, Rademeyer, Cecilia, Raikanikoda, Filimone, Rayfield, Mark A, Reynes, Jean-Marc, Rinke de Wit, Tobias, Robbins, Kenneth E, Rolland, Morgane, Rousseau, Christine, Salazar-Gonzales, Jesus, Salem, Hanan, Salminen, Mika, Salomon, Horacio, Sandstrom, Paul, Santiago, Mario L, Sarr, Abdoulaye D, Schroeder, Bryan, Segondy, Michel, Selhorst, Philippe, Sempala, Sylvester, Servais, Jean, Shaik, Ansari, Shao, Yiming, Slim, Amine, Soares, Marcelo A, Songok, Elijah, Stewart, Debbie, Stokes, Julie, Subbarao, Shambavi, Sutthent, Ruengpung, Takehisa, Jun, Tanuri, Amilcar, Tee, Kok Keng, Thapa, Kiran, Thomson, Michael, Tran, Tyna, Urassa, Willy, Ushijima, Hiroshi, van de Perre, Philippe, van der Groen, Guido, van Laethem, Kristel, van Oosterhout, Joep, van Sighem, Ard, van Wijngaerden, Eric, Vandamme, Anne-Mieke, Vercauteren, Jurgen, Vidal, Nicole, Wallace, Lesley, Williamson, Carolyn, Wolday, Dawit, Xu, Jianqing, Yang, Chunfu, Zhang, Linqi, Zhang, Rong, Hemelaar, Joris, Elangovan, Ramyiadarsini, Yun, Jason, Dickson-Tetteh, Leslie, Fleminger, Isabella, Kirtley, Shona, Williams, Brian, Gouws-Williams, Eleanor, and Ghys, Peter D

Published
2019
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12. HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing.

Author

Rhee, Soo-Yon, Jordan, Michael R, Raizes, Elliot, Chua, Arlene, Parkin, Neil, Kantor, Rami, Van Zyl, Gert U, Mukui, Irene, Hosseinipour, Mina C, Frenkel, Lisa M, Ndembi, Nicaise, Hamers, Raph L, Rinke de Wit, Tobias F, Wallis, Carole L, Gupta, Ravindra K, Fokam, Joseph, Zeh, Clement, Schapiro, Jonathan M, Carmona, Sergio, Katzenstein, David, Tang, Michele, Aghokeng, Avelin F, De Oliveira, Tulio, Wensing, Annemarie MJ, Gallant, Joel E, Wainberg, Mark A, Richman, Douglas D, Fitzgibbon, Joseph E, Schito, Marco, Bertagnolio, Silvia, Yang, Chunfu, and Shafer, Robert W

Subjects
Humans, HIV-1, HIV Infections, Ritonavir, Reverse Transcriptase Inhibitors, Protease Inhibitors, Treatment Failure, Drug Therapy, Combination, Drug Resistance, Viral, Mutation, Point-of-Care Systems, Lopinavir, Genotyping Techniques, Darunavir, Atazanavir Sulfate, Drug Therapy, Combination, Drug Resistance, Viral, General Science & Technology, MD Multidisciplinary
Abstract

The increasing prevalence of acquired and transmitted HIV-1 drug resistance is an obstacle to successful antiretroviral therapy (ART) in the low- and middle-income countries (LMICs) hardest hit by the HIV-1 pandemic. Genotypic drug resistance testing could facilitate the choice of initial ART in areas with rising transmitted drug resistance (TDR) and enable care-providers to determine which individuals with virological failure (VF) on a first- or second-line ART regimen require a change in treatment. An inexpensive near point-of-care (POC) genotypic resistance test would be useful in settings where the resources, capacity, and infrastructure to perform standard genotypic drug resistance testing are limited. Such a test would be particularly useful in conjunction with the POC HIV-1 viral load tests that are currently being introduced in LMICs. A POC genotypic resistance test is likely to involve the use of allele-specific point mutation assays for detecting drug-resistance mutations (DRMs). This study proposes that two major nucleoside reverse transcriptase inhibitor (NRTI)-associated DRMs (M184V and K65R) and four major NNRTI-associated DRMs (K103N, Y181C, G190A, and V106M) would be the most useful for POC genotypic resistance testing in LMIC settings. One or more of these six DRMs was present in 61.2% of analyzed virus sequences from ART-naïve individuals with intermediate or high-level TDR and 98.8% of analyzed virus sequences from individuals on a first-line NRTI/NNRTI-containing regimen with intermediate or high-level acquired drug resistance. The detection of one or more of these DRMs in an ART-naïve individual or in a individual with VF on a first-line NRTI/NNRTI-containing regimen may be considered an indication for a protease inhibitor (PI)-containing regimen or closer virological monitoring based on cost-effectiveness or country policy.

Published
2015

14. HIV-1 drug resistance before initiation or re-initiation of first-line antiretroviral therapy in low-income and middle-income countries: a systematic review and meta-regression analysis

Author

Gupta, Ravindra K, Gregson, John, Parkin, Neil, Haile-Selassie, Hiwot, Tanuri, Amilcar, Andrade Forero, Liliana, Kaleebu, Pontiano, Watera, Christine, Aghokeng, Avelin, Mutenda, Nicholus, Dzangare, Janet, Hone, San, Hang, Zaw Zaw, Garcia, Judith, Garcia, Zully, Marchorro, Paola, Beteta, Enrique, Giron, Amalia, Hamers, Raph, Inzaule, Seth, Frenkel, Lisa M, Chung, Michael H, de Oliveira, Tulio, Pillay, Deenan, Naidoo, Kogie, Kharsany, Ayesha, Kugathasan, Ruthiran, Cutino, Teresa, Hunt, Gillian, Avila Rios, Santiago, Doherty, Meg, Jordan, Michael R, and Bertagnolio, Silvia

Published
2018
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17. Viral Phenotypic Resistance Assays

Author

Reeves, Jacqueline D., Parkin, Neil T., Mayers, Douglas L., editor, Sobel, Jack D., editor, Ouellette, Marc, editor, Kaye, Keith S., editor, and Marchaim, Dror, editor

Published
2017
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18. Human Immunodeficiency Virus (HIV) Drug Resistance in African Infants and Young Children Newly Diagnosed With HIV : A Multicountry Analysis

Author

Jordan, Michael R., Penazzato, Martina, Cournil, Amandine, Vubil, Adolfo, Jani, Ilesh, Hunt, Gillian, Carmona, Sergio, Maphalala, Gugu, Mthethwa, Nobuhle, Watera, Christine, Kaleebu, Pontiano, Musanhu, Christine Chakanyuka, Mtapuri-Zinyowera, Sekesai, Dzangare, Janet, Peeters, Martine, Yang, Chunfu, Parkin, Neil, and Bertagnolio, Silvia

Published
2017

21. High levels of HIV drug resistance among adults failing second-line antiretroviral therapy in Namibia

Author

Jordan, Michael R., Hamunime, Ndapewa, Bikinesi, Leonard, Sawadogo, Souleymane, Agolory, Simon, Shiningavamwe, Andreas N., Negussie, Taffa, Fisher-Walker, Christa L., Raizes, Elliot G., Mutenda, Nicholus, Hunter, Christian J., Dean, Natalie, Steegen, Kim, Kana, Vibha, Carmona, Sergio, Yang, Chunfu, Tang, Alice M., Parkin, Neil, and Hong, Steven Y.

Published
2020
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22. Bioinformatic data processing pipelines in support of next-generation sequencing-based HIV drug resistance testing: the Winnipeg Consensus

Author

Ji, Hezhao, Enns, Eric, Brumme, Chanson J., Parkin, Neil, Howison, Mark, Lee, Emma R., Capina, Rupert, Marinier, Eric, Avila-Rios, Santiago, Sandstrom, Paul, Domselaar, Gary Van, Harrigan, Richard, Paredes, Roger, Kantor, Rami, and Noguera-Julian, Marc

Subjects
HIV infections -- Drug therapy, DNA sequencing -- Research, Drug resistance -- Genetic aspects -- Research, Medical research, Medical informatics -- Standards, Health
Abstract

Introduction: Next-generation sequencing (NGS) has several advantages over conventional Sanger sequencing for HIV drug resistance (HIVDR) genotyping, including detection and quantitation of low-abundance variants bearing drug resistance mutations (DRMs). However, the high HIV genomic diversity, unprecedented large volume of data, complexity of analysis and potential for error pose significant challenges for data processing. Several NGS analysis pipelines have been developed and used in HIVDR research; however, the absence of uniformity in data processing strategies results in lack of consistency and comparability of outputs from different pipelines. To fill this gap, an international symposium on bioinformatic strategies for NGS-based HIVDR testing was held in February 2018 in Winnipeg, Canada, convening laboratory scientists, bioinformaticians and clinicians involved in four recently developed, publicly available NGS HIVDR pipelines. The goal of this symposium was to establish a consensus on effective bioinformatic strategies for NGS data management and its use for HIVDR reporting. Discussion: Essential functionalities of an NGS HIVDR pipeline were divided into five analytic blocks: (1) NGS read quality control (QC)/quality assurance (QA); (2) NGS read alignment and reference mapping; (3) HIV variant calling and variant QC; (4) NGS HIVDR reporting; and (5) extended data applications and additional considerations for data management. The consensuses reached among the participants on all major aspects of these blocks are summarized here. They encompass not only recommended data management and analysis strategies, but also detailed bioinformatic approaches that help ensure accuracy of the derived HIVDR analysis outputs for both research and potential clinical use. Conclusions: While NGS is being adopted more broadly in HIVDR testing laboratories, data processing is often a bottleneck hindering its generalized application. The proposed standardization of NGS read QC/QA, read alignment and reference mapping, variant calling and QC, HIVDR reporting and relevant data management strategies in this 'Winnipeg Consensus' may serve as a starting guideline for NGS HIVDR data processing that informs the refinement of existing pipelines and those yet to be developed. Moreover, the bioinformatic strategies presented here may apply more broadly to NGS data analysis of microbes harbouring significant genomic diversity. Keywords: next-generation sequencing; HIV drug resistance test; bioinformatics; pipeline; Winnipeg Consensus; guideline, 1 | INTRODUCTION Successful antiretroviral therapy (ART) suppresses HIV viral load, reduces the incidence of new infections and increases the life expectancy of infected individuals [1-5]. However, HIV drug resistance [...]

Published
2018
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23. Performance comparison of next generation sequencing analysis pipelines for HIV-1 drug resistance testing

Author

Lee, Emma R., Parkin, Neil, Jennings, Cheryl, Brumme, Chanson J., Enns, Eric, Casadellà, Maria, Howison, Mark, Coetzer, Mia, Avila-Rios, Santiago, Capina, Rupert, Marinier, Eric, Van Domselaar, Gary, Noguera-Julian, Marc, Kirkby, Don, Knaggs, Jeff, Harrigan, Richard, Quiñones-Mateu, Miguel, Paredes, Roger, Kantor, Rami, Sandstrom, Paul, and Ji, Hezhao

Published
2020
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26. Infrequent Development of Resistance in Genotype 1–6 Hepatitis C Virus–Infected Subjects Treated With Sofosbuvir in Phase 2 and 3 Clinical Trials

Author

Svarovskaia, Evguenia S., Dvory-Sobol, Hadas, Parkin, Neil, Hebner, Christy, Gontcharova, Viktoria, Martin, Ross, Ouyang, Wen, Han, Bin, Xu, Simin, Ku, Karin, Chiu, Sophia, Gane, Edward, Jacobson, Ira M., Nelson, David R., Lawitz, Eric, Wyles, David L., Bekele, Neby, Brainard, Diana, Symonds, William T., McHutchison, John G., Miller, Michael D., and Mo, Hongmei

Published
2014

29. Facilitating Next‐Generation Pre‐Exposure Prophylaxis Clinical Trials Using HIV Recent Infection Assays: A Consensus Statement from the Forum HIV Prevention Trial Design Project.

Author

Parkin, Neil, Gao, Fei, Grebe, Eduard, Cutrell, Amy, Das, Moupali, Donnell, Deborah, Duerr, Ann, Glidden, David V., Hughes, James P., Murray, Jeffrey, Robertson, Michael N., Zinserling, Joerg, Lau, Joseph, Miller, Veronica, Pottinger, Yen, Lehnert, Regine, Mastro, Timothy D., Grinsztejn, Beatriz, Tchelidze, Tamar, and Baeten, Jared

Subjects
HIV prevention, HIV infections, PRE-exposure prophylaxis, HIV, CLINICAL trials, AIDS vaccines
Abstract

Standard‐of‐care HIV pre‐exposure prophylaxis (PrEP) is highly efficacious, but uptake of and persistence on a daily oral pill is low in many settings. Evaluation of alternate PrEP products will require innovation to avoid the unpractically large sample sizes in noninferiority trials. We propose estimating HIV incidence in people not on PrEP as an external counterfactual to which on‐PrEP incidence in trial subjects can be compared. HIV recent infection testing algorithms (RITAs), such as the limiting antigen avidity assay plus viral load used on specimens from untreated HIV positive people identified during screening, is one possible approach. Its feasibility is partly dependent on the sample size needed to ensure adequate power, which is impacted by RITA performance, the number of recent infections identified, the expected efficacy of the intervention, and other factors. Screening sample sizes to support detection of an 80% reduction in incidence for 3 key populations are more modest, and comparable to the number of participants in recent phase III PrEP trials. Sample sizes would be significantly larger in populations with lower incidence, where the false recency rate is higher or if PrEP efficacy is expected to be lower. Our proposed counterfactual approach appears to be feasible, offers high statistical power, and is nearly contemporaneous with the on‐PrEP population. It will be important to monitor the performance of this approach during new product development for HIV prevention. If successful, it could be a model for preventive HIV vaccines and prevention of other infectious diseases. [ABSTRACT FROM AUTHOR]

Published
2023
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32. Locating blockages in buried (telecoms) ducts: a new approach

Author

Metje, Nicole, primary, Chapman, David, additional, Stringfellow, Matt, additional, Rebegea, Simina, additional, Tuckwell, George, additional, Guy, Matt, additional, Parkin, Neil, additional, Roberts, Daniel, additional, Leech, Chris, additional, and Lord, Andrew, additional

Published
2022
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35. Sequence and Phenotypic Analysis for Resistance Monitoring in Hepatitis C Virus Drug Development: Recommendations From the HCV DRAG

Author

Kwong, Ann D., Najera, Isabel, Bechtel, Jill, Bowden, Scott, Fitzgibbon, Joseph, Harrington, Patrick, Kempf, Dale, Kieffer, Tara L., Koletzki, Diana, Kukolj, George, Lim, Sharlene, Pilot–Matias, Tami, Lin, Kai, Mani, Nina, Mo, Hongmei, O'Rear, Jules, Otto, Michael, Parkin, Neil, Pawlotsky, Jean–Michel, Petropoulos, Chris, Picchio, Gaston, Ralston, Robert, Reeves, Jacqueline D., Schooley, Robert T., Seiwert, Scott, Standring, David, Stuyver, Lieven, Sullivan, James, and Miller, Veronica

Published
2011
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42. Integrase strand transfer inhibitor (INSTI)-resistance mutations for the surveillance of transmitted HIV-1 drug resistance

Author

Tzou, Philip L, Rhee, Soo-Yon, Descamps, Diane, Clutter, Dana S, Hare, Bradley, Mor, Orna, Grude, Maxime, Parkin, Neil, Jordan, Michael R, Bertagnolio, Silvia, Schapiro, Jonathan M, Harrigan, P Richard, Geretti, Anna Maria, Marcelin, Anne-Genevieve, Shafer, Robert W, and Grp, WHO HIVResNet Working

Subjects
0301 basic medicine, Microbiology (medical), Genotype, Pyridones, 030106 microbiology, Human immunodeficiency virus (HIV), Integrase inhibitor, HIV Infections, HIV Integrase, Drug resistance, medicine.disease_cause, Piperazines, 03 medical and health sciences, chemistry.chemical_compound, Drug Resistance, Viral, Oxazines, Prevalence, medicine, Humans, Gene Regulatory Networks, Pharmacology (medical), HIV Integrase Inhibitors, Original Research, Pharmacology, Mutation, biology, Transmission (medicine), Virology, Integrase, Integrase strand transfer inhibitor, Phenotype, 030104 developmental biology, Infectious Diseases, chemistry, Epidemiological Monitoring, Dolutegravir, HIV-1, biology.protein, Heterocyclic Compounds, 3-Ring
Abstract

Background Integrase strand transfer inhibitors (INSTIs) are expected to be widely adopted globally, requiring surveillance of resistance emergence and transmission. Objectives We therefore sought to develop a standardized list of INSTI-resistance mutations suitable for the surveillance of transmitted INSTI resistance. Methods To characterize the suitability of the INSTI-resistance mutations for transmitted HIV-1 drug resistance (TDR) surveillance, we classified them according to their presence on published expert lists, conservation in INSTI-naive persons, frequency in INSTI-treated persons and contribution to reduced in vitro susceptibility. Mutation prevalences were determined using integrase sequences from 17302 INSTI-naive and 2450 INSTI-treated persons; 53.3% of the INSTI-naive sequences and 20.0% of INSTI-treated sequences were from non-B subtypes. Approximately 10% of sequences were from persons who received dolutegravir alone or a first-generation INSTI followed by dolutegravir. Results Fifty-nine previously recognized (or established) INSTI-resistance mutations were present on one or more of four published expert lists. They were classified into three main non-overlapping groups: 29 relatively common non-polymorphic mutations, occurring in five or more individuals and significantly selected by INSTI treatment; 8 polymorphic mutations; and 22 rare mutations. Among the 29 relatively common INSTI-selected mutations, 24 emerged as candidates for inclusion on a list of INSTI surveillance drug-resistance mutations: T66A/I/K, E92G/Q, G118R, F121Y, E138A/K/T, G140A/C/S, Y143C/H/R/S, S147G, Q148H/R/K, N155H, S230R and R263K. Conclusions A set of 24 non-polymorphic INSTI-selected mutations is likely to be useful for quantifying INSTI-associated TDR. This list may require updating as more sequences become available from INSTI-experienced persons infected with HIV-1 non-subtype B viruses and/or receiving dolutegravir.

Published
2019
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