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2. Low frequency of genotypic resistance in HIV-1-infected patients failing an atazanavir-containing regimen: a clinical cohort study

Author

Dolling, David I, Dunn, David T, Sutherland, Katherine A, Pillay, Deenan, Mbisa, Jean L, Parry, Chris M, Post, Frank A, Sabin, Caroline A, Cane, Patricia A, Aitken, Celia, Asboe, David, Webster, Daniel, Cane, Patricia, Castro, Hannah, Dunn, David, Dolling, David, Chadwick, David, Churchill, Duncan, Clark, Duncan, Collins, Simon, Delpech, Valerie, Geretti, Anna Maria, Goldberg, David, Hale, Antony, Hué, Stéphane, Kaye, Steve, Kellam, Paul, Lazarus, Linda, Leigh-Brown, Andrew, Mackie, Nicola, Orkin, Chloe, Rice, Philip, Phillips, Andrew, Sabin, Caroline, Smit, Erasmus, Templeton, Kate, Tilston, Peter, Tong, William, Williams, Ian, Zhang, Hongyi, Zuckerman, Mark, Greatorex, Jane, Wildfire, Adrian, O'Shea, Siobhan, Mullen, Jane, Mbisa, Tamyo, Cox, Alison, Tandy, Richard, Hale, Tony, Fawcett, Tracy, Hopkins, Mark, Ashton, Lynn, Booth, Claire, Garcia-Diaz, Ana, Shepherd, Jill, Schmid, Matthias L, Payne, Brendan, Hay, Phillip, Rice, Phillip, Paynter, Mary, Bibby, David, Kirk, Stuart, MacLean, Alasdair, Gunson, Rory, Coughlin, Kate, Fearnhill, Esther, Fradette, Lorraine, Porter, Kholoud, Ainsworth, Jonathan, Anderson, Jane, Babiker, Abdel, Fisher, Martin, Gazzard, Brian, Gilson, Richard, Gompels, Mark, Hill, Teresa, Johnson, Margaret, Kegg, Stephen, Leen, Clifford, Nelson, Mark, Palfreeman, Adrian, Post, Frank, Sachikonye, Memory, Schwenk, Achim, Walsh, John, Huntington, Susie, Jose, Sophie, Thornton, Alicia, Glabay, Adam, Orkin, C, Garrett, N, Lynch, J, Hand, J, de Souza, C, Fisher, M, Perry, N, Tilbury, S, Gazzard, B, and Nelson, M

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Clinical Sciences, Clinical Trials and Supportive Activities, Infectious Diseases, Antimicrobial Resistance, Clinical Research, Infection, Adult, Anti-HIV Agents, Atazanavir Sulfate, Cohort Studies, Drug Resistance, Viral, Female, HIV Infections, HIV Protease, HIV-1, Humans, Male, Medication Adherence, Middle Aged, Mutation Rate, Mutation, Missense, Oligopeptides, Pyridines, Treatment Failure, United States, UK HIV Drug Resistance Database, UK Collaborative HIV Cohort Study, HIV, drug resistance mutations, naive patients, protease inhibitors, virological failure, Microbiology, Pharmacology and Pharmaceutical Sciences, Clinical sciences, Pharmacology and pharmaceutical sciences
Abstract

ObjectivesTo determine protease mutations that develop at viral failure for protease inhibitor (PI)-naive patients on a regimen containing the PI atazanavir.MethodsResistance tests on patients failing atazanavir, conducted as part of routine clinical care in a multicentre observational study, were randomly matched by subtype to resistance tests from PI-naive controls to account for natural polymorphisms. Mutations from the consensus B sequence across the protease region were analysed for association and defined using the IAS-USA 2011 classification list.ResultsFour hundred and five of 2528 (16%) patients failed therapy containing atazanavir as a first PI over a median (IQR) follow-up of 1.76 (0.84-3.15) years and 322 resistance tests were available for analysis. Recognized major atazanavir mutations were found in six atazanavir-experienced patients (P < 0.001), including I50L and N88S. The minor mutations most strongly associated with atazanavir experience were M36I, M46I, F53L, A71V, V82T and I85V (P < 0.05). Multiple novel mutations, I15S, L19T, K43T, L63P/V, K70Q, V77I and L89I/T/V, were also associated with atazanavir experience.ConclusionsViral failure on atazanavir-containing regimens was not common and major resistance mutations were rare, suggesting that adherence may be a major contributor to viral failure. Novel mutations were described that have not been previously documented.

Published
2013

3. An Overview of SARS-CoV-2 Molecular Diagnostics in Europe

Author

Davies, Emma, primary, Farooq, Hamzah Z., additional, Brown, Benjamin, additional, Tilston, Peter, additional, McEwan, Ashley, additional, Birtles, Andrew, additional, O’Hara, Robert William, additional, Ahmad, Shazaad, additional, Machin, Nicholas, additional, Hesketh, Louise, additional, and Guiver, Malcolm, additional

Published
2022
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4. Recent trends and patterns in HIV‐1 transmitted drug resistance in the United Kingdom

Author

Tostevin, A, White, E, Dunn, D, Croxford, S, Delpech, V, Williams, I, Asboe, D, Pozniak, A, Churchill, D, Geretti, AM, Pillay, D, Sabin, C, LeighBrown, A, Smit, E, Aitken, Celia, Cane, Patricia, Chadwick, David, Clark, Duncan, Collins, Simon, Douthwaite, Samuel, Fearnhill, Esther, Porter, Kholoud, Fraser, Christophe, Hale, Antony, Hué, Stéphane, Kaye, Steve, Kellam, Paul, Lazarus, Linda, Mbisa, Tamyo, Mackie, Nicola, Moses, Samuel, Orkin, Chloe, Nastouli, Eleni, Phillips, Andrew, Templeton, Kate, Tilston, Peter, Zhang, Hongyi, Fairbrother, Keith, Greatorex, Jane, OʼShea, Siobhan, Mullen, Jane, Cox, Alison, Tandy, Richard, Fawcett, Tracy, Hopkins, Mark, Ashton, Lynne, Booth, Clare, GarciaDiaz, Ana, Shepherd, Jill, Schmid, Matthias L., Payne, Brendan, Pereira, Spiro, Hubb, Jonathan, Kirk, Stuart, Gunson, Rory, and BradleyStewart, Amanda

Published
2017
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5. Real-world SARS CoV-2 testing in Northern England during the first wave of the COVID-19 pandemic

Author

Farooq, Hamzah Z., primary, Davies, Emma, additional, Brown, Benjamin, additional, Whitfield, Thomas, additional, Tilston, Peter, additional, McEwan, Ashley, additional, Birtles, Andrew, additional, O'Hara, Robert, additional, Spencer, Hannah, additional, Hesketh, Louise, additional, Ahmad, Shazaad, additional, Guiver, Malcolm, additional, and Machin, Nicholas, additional

Published
2021
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6. Detection of drug resistance mutations at low plasma HIV-1 RNA load in a European multicentre cohort study

Author

Prosperi, Mattia C. F., Mackie, Nicola, Di Giambenedetto, Simona, Zazzi, Maurizio, Camacho, Ricardo, Fanti, Iuri, Torti, Carlo, Sönnerborg, Anders, Kaiser, Rolf, Codoñer, Francisco M., Van Laethem, Kristel, Bansi, Loveleen, van de Vijver, David A. M. C., Geretti, Anna Maria, De Luca, Andrea, Giacometti, Andrea, Butini, Luca, del Gobbo, Romana, Menzo, Stefano, Tacconi, Danilo, Corbelli, Giovanni, Zanussi, Stefania, Monno, Laura, Punzi, Grazia, Maggiolo, Franco, Callegaro, Annapaola, Calza, Leonardo, Carla Re, Maria, Pristerà, Raffaele, Turconi, Paola, Mandas, Antonella, Tini, Sauro, Zoncada, Alessia, Paolini, Elisabetta, Amadio, Giorgio, Sighinolfi, Laura, Zuccati, Giuliano, Morfini, Massimo, Manetti, Roberto, Corsi, Paola, Galli, Luisa, Di Pietro, Massimo, Bartalesi, Filippo, Colao, Grazia, Tosti, Andrea, Di Biagio, Antonio, Setti, Maurizio, Bruzzone, Bianca, Penco, Giovanni, Trezzi, Michele, Orani, Anna, Pardelli, Riccardo, De Gennaro, Michele, Chiodera, Alessandro, Scalzini, Alfredo, Palvarini, Loredana, Almi, Paolo, Todaro, Giovanni, dʼArminio Monforte, Antonella, Cicconi, Paola, Rusconi, Stefano, Gismondo, Maria Rita, Gismondo, Maria Rita, Micheli, Valeria, Biondi, Maria Luisa, Gianotti, Nicola, Capetti, Amedeo, Meraviglia, Paola, Boeri, Enzo, Mussini, Cristina, Pecorari, Monica, Soria, Alessandro, Vecchi, Laura, Santirocchi, Maurizio, Brustia, Diego, Ravanini, Paolo, Bello, Federico Dal, Romano, Nino, Mancuso, Salvatrice, Calzetti, Carlo, Maserati, Renato, Filice, Gaetano, Baldanti, Fausto, Francisci, Daniela, Parruti, Giustino, Polilli, Ennio, Sacchini, Daria, Martinelli, Chiara, Consolini, Rita, Vatteroni, Linda, Vivarelli, Angela, Dionisio, Daniele, Nerli, Alessandro, Lenzi, Lucia, Magnani, Giacomo, Ortolani, Patrizia, Andreoni, Massimo, Palamara, Guido, Fimiani, Caterina, Palmisano, Lucia, De Luca, Andrea, Fadda, Giovanni, Vullo, Vincenzo, Turriziani, Ombretta, Montano, Marco, Cenderello, Giovanni, Gonnelli, Angela, Zazzi, Maurizio, Palumbo, Michele, Ghisetti, Valeria, Bonora, Stefano, Foglie, Palma Delle, Rossi, Cristina, Grossi, Paolo, Seminari, Elena, Poletti, Federica, Mondino, Vincenzo, Malena, Marina, Lattuada, Emanuela, Lengauer, Thomas, Däumer, Martin, Hoffmann, Daniel, Kaiser, Rolf, Schülter, Eugen, Müller, Claudia, Oette, Mark, Reuter, Stefan, Esser, Stefan, Fätkenheuer, Gerd, Rockstroh, Jürgen, van de Vijver, David AMC, Incardona, Francesca, Rosen-Zvi, Michal, Lengauer, Thomas, Camacho, Ricardo, Clotet, Bonaventura, Thalme, Anders, Svedhem, Veronica, Bratt, Göran, Gargiulo, Franco, Lapadula, Giuseppe, Manca, Nino, Paraninfo, Giuseppe, Quiros-Roldan, Eugenia, Carosi, Giampiero, Castelnuovo, Filippo, Vandamme, Anne-Mieke, Van Laethem, Kristel, Van Wijngaerden, Eric, Ainsworth, Jonathan, Anderson, Jane, Babiker, Abdel, Dunn, David, Easterbrook, Philippa, Fisher, Martin, Gazzard, Brian, Garrett, Nigel, Gilson, Richard, Gompels, Mark, Hill, Teresa, Johnson, Margaret, Leen, Clifford, Orkin, Chloe, Phillips, Andrew, Pillay, Deenan, Porter, Kholoud, Post, Frank, Sabin, Caroline, Sadiq, Tariq, Schwenk, Achim, Walsh, John, Delpech, Valerie, Palfreeman, Adrian, Dunn, David, Glabay, Adam, Porter, Kholoud, Bansi, Loveleen, Hill, Teresa, Phillips, Andrew, Sabin, Caroline, Orkin, Chloe, Garrett, Nigel, Lynch, Janet, Hand, James, de Souza, Carl, Fisher, Martin, Perry, Nicky, Tilbury, Stuart, Churchill, Duncan, Gazzard, Brian, Nelson, Mark, Waxman, Matthew, Mandalia, Sundhiya, Delpech, Valerie, Anderson, Jane, Kall, Meaghan, Post, Frank, Korat, Hardik, Taylor, Chris, Ibrahim, Fowzia, Campbell, Lucy, Easterbrook, Philippa, Babiker, Abdel, Dunn, David, Glabay, Adam, Porter, Kholoud, Gilson, Richard, James, Laura, Brima, Nataliya, Williams, Ian, Schwenk, Achim, Johnson, Margaret, Youle, Mike, Lampe, Fiona, Smith, Colette, Grabowska, Helen, Chaloner, Clinton, Puradiredja, Dewi Ismajani, Bansi, Loveleen, Hill, Teresa, Phillips, Andrew, Sabin, Caroline, Walsh, John, Weber, Jonathan, Ramzan, Farhan, Carder, Mark, Leen, Clifford, Wilson, Alan, Gompels, Mark, Dooley, Debbie, Palfreeman, Adrian, Anderson, Jane, Asboe, David, Pozniak, Anton, Cameron, Sheila, Cane, Patricia, Chadwick, David, Churchill, Duncan, Clark, Duncan, Collins, Simon, Delpech, Valerie, Pillay, Deenan, Lazarus, Linda, Dunn, David, Dolling, David, Fearnhill, Esther, Castro, Hannah, Porter, Kholoud, Coughlin, Kate, Dolling, David, Zuckerman, Mark, Anna Maria, Geretti, Booth, Clare, Goldberg, David, Gompels, Mark, Hale, Antony, Kaye, Steve, Kellam, Paul, Leigh-Brown, Andrew, Mackie, Nicola, Orkin, Chloe, Pillay, Deenan, Phillips, Andrew, Sabin, Caroline, Smit, Erasmus, Templeton, Kate, Tilston, Peter, Tong, William, Williams, Ian, Zhang, Hongyi, Zhang, Hongyi, Clark, Duncan, Ushiro-Lumb, Ines, Oliver, Tony, Bibby, David, Mitchell, Suzanne, Smit, Erasmus, Mbisa, Tamyo, Wildfire, Adrian, Tandy, Richard, Shepherd, Jill, Chadwick, David, MacLean, Alasdair, Tong, William, Bennett, Diane, Hopkins, Mark, Tilston, Peter, Booth, Clare, Garcia-Diaz, Ana, Kaye, Steve, and Kirk, Stuart

Published
2011
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9. Associations between baseline characteristics, CD4 cell count response and virological failure on first-line efavirenz + tenofovir + emtricitabine for HIV

Author

Stirrup, Oliver T., primary, Sabin, Caroline A., additional, Phillips, Andrew N., additional, Williams, Ian, additional, Churchill, Duncan, additional, Tostevin, Anna, additional, Hill, Teresa, additional, Dunn, David T., additional, Asboe, David, additional, Pozniak, Anton, additional, Cane, Patricia, additional, Chadwick, David, additional, Clark, Duncan, additional, Collins, Simon, additional, Delpech, Valerie, additional, Douthwaite, Samuel, additional, Dunn, David, additional, Fearnhill, Esther, additional, Porter, Kholoud, additional, Stirrup, Oliver, additional, Fraser, Christophe, additional, Geretti, Anna Maria, additional, Gunson, Rory, additional, Hale, Antony, additional, Hué, Stéphane, additional, Lazarus, Linda, additional, Leigh-Brown, Andrew, additional, Mbisa, Tamyo, additional, Mackie, Nicola, additional, Orkin, Chloe, additional, Nastouli, Eleni, additional, Pillay, Deenan, additional, Phillips, Andrew, additional, Sabin, Caroline, additional, Smit, Erasmus, additional, Templeton, Kate, additional, Tilston, Peter, additional, Volz, Erik, additional, Zhang, Hongyi, additional, Fairbrother, Keith, additional, Dawkins, Justine, additional, O’Shea, Siobhan, additional, Mullen, Jane, additional, Cox, Alison, additional, Tandy, Richard, additional, Fawcett, Tracy, additional, Hopkins, Mark, additional, Booth, Clare, additional, Renwick, Lynne, additional, Schmid, Matthias L., additional, Payne, Brendan, additional, Hubb, Jonathan, additional, Dustan, Simon, additional, Kirk, Stuart, additional, Bradley-Stewart, Amanda, additional, Jose, Sophie, additional, Thornton, Alicia, additional, Huntington, Susie, additional, Glabay, Adam, additional, Shidfar, Shaadi, additional, Lynch, Janet, additional, Hand, James, additional, de Souza, Carl, additional, Perry, Nicky, additional, Tilbury, Stuart, additional, Youssef, Elaney, additional, Gazzard, Brian, additional, Nelson, Mark, additional, Mabika, Tracey, additional, Mandalia, Sundhiya, additional, Anderson, Jane, additional, Munshi, Sajid, additional, Post, Frank, additional, Adefisan, Ade, additional, Taylor, Chris, additional, Gleisner, Zachary, additional, Ibrahim, Fowzia, additional, Campbell, Lucy, additional, Baillie, Kirsty, additional, Gilson, Richard, additional, Brima, Nataliya, additional, Ainsworth, Jonathan, additional, Schwenk, Achim, additional, Miller, Sheila, additional, Wood, Chris, additional, Johnson, Margaret, additional, Youle, Mike, additional, Lampe, Fiona, additional, Smith, Colette, additional, Tsintas, Rob, additional, Chaloner, Clinton, additional, Hutchinson, Samantha, additional, Walsh, John, additional, Mackie, Nicky, additional, Winston, Alan, additional, Weber, Jonathan, additional, Ramzan, Farhan, additional, Carder, Mark, additional, Leen, Clifford, additional, Wilson, Alan, additional, Morris, Sheila, additional, Gompels, Mark, additional, Allan, Sue, additional, Palfreeman, Adrian, additional, Lewszuk, Adam, additional, Kegg, Stephen, additional, Faleye, Akin, additional, Ogunbiyi, Victoria, additional, Mitchell, Sue, additional, Hay, Phillip, additional, Kemble, Christian, additional, Martin, Fabiola, additional, Russell-Sharpe, Sarah, additional, Gravely, Janet, additional, Allan, Sris, additional, Harte, Andrew, additional, Tariq, Anjum, additional, Spencer, Hazel, additional, Jones, Ron, additional, Pritchard, Jillian, additional, Cumming, Shirley, additional, Atkinson, Claire, additional, Mital, Dushyant, additional, Edgell, Veronica, additional, Allen, Juli, additional, Ustianowski, Andy, additional, Murphy, Cynthia, additional, Gunder, Ilise, additional, Trevelion, Roy, additional, and Babiker, Abdel, additional

Published
2019
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10. Virological failure and development of new resistance mutations according to CD4 count at combination antiretroviral therapy initiation

Author

Jose, S., Quinn, K., Dunn, D., Cox, A., Sabin, C., Fidler, S., Fisher, Martin, Gazzard, Brian, Gilson, Richard, Gompels, Mark, Hay, Phillip, Johnson, Margaret, Kegg, Stephen, Leen, C., Martin, Fabiola, Nelson, Mark, Palfreeman, Adrian, Post, F., Pritchard, Jillian, Sachikonye, Memory, Schwenk, Achim, Tariq, Anjum, Walsh, John, Hill, Teresa, Jose, Sophie, Phillips, Andrew, Sabin, Caroline, Thornton, Alicia, Dunn, David, Glabay, Adam, Fisher, M., Perry, N., Tilbury, S., Youssef, E., Churchill, D., Gazzard, B., Nelson, M., Everett, R., Asboe, D., Mandalia, S., Korat, H., Taylor, C., Gleisner, Z., Ibrahim, F., Campbell, L., Gilson, R., Brima, N., Williams, I., Johnson, M., Youle, M., Lampe, F., Smith, C., Tsintas, R., Chaloner, C., Hutchinson, S., Phillips, A., Hill, T., Thornton, A., Huntington, S., Walsh, J., Mackie, N., Winston, A., Weber, J., Ramzan, F., Carder, M., Orkin, C., Lynch, J., Hand, J., de Souza, C., Anderson, J., Munshi, S., Ainsworth, J., Schwenk, A., Miller, S., Wood, C., Wilson, A., Morris, S., Gompels, M., Allan, S., Palfreeman, A., Memon, K., Lewszuk, A., Chadwick, D., Cope, E., Gibson, J., Kegg, S., Main, P., Mitchell, Hunter, Hay, P., Dhillon, M., Martin, F., Russell-Sharpe, S., Harte, A., Clay, S., Tariq, A., Spencer, H., Jones, R., Pritchard, J., Cumming, S., Atkinson, C., Delpech, Valerie, Sachikony, M., Aitken, Celia, Asboe, David, Pozniak, Anton, Cane, Patricia, Chadwick, David, Churchill, Duncan, Clark, Duncan, Collins, Simon, Douthwaite, Samuel, Fearnhill, Esther, Porter, Kholoud, Tostevin, Anna, White, Ellen, Fraser, Christophe, Geretti, Anna Maria, Hale, Antony, Hué, Stéphane, Kaye, Steve, Kellam, Paul, Lazarus, Linda, Leigh-Brown, Andrew, Mbisa, Tamyo, Mackie, Nicola, Moses, Samuel, Orkin, Chloe, Nastouli, Eleni, Pillay, Deenan, Smit, Erasmus, Templeton, Kate, Tilston, Peter, Webster, Daniel, Williams, Ian, Zhang, Hongyi, Greatorex, Jane, O'Shea, Siobhan, Mullen, Jane, Cox, Alison, Tandy, Richard, Fawcett, Tracy, Hopkins, Mark, Ashton, Lynn, Booth, Claire, Garcia-Diaz, Ana, Shepherd, Jill, Schmid, Matthias L., Payne, Brendan, Pereira, Spiro, Hubb, Jonathan, Kirk, Stuart, Gunson, Rory, Bradley-Stewart, Amanda, and Medical Research Council (MRC)

Subjects
0301 basic medicine, Male, HAART, HIV Infections, Treatment failure, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Antiretroviral Therapy, Highly Active, Pharmacology (medical), 030212 general & internal medicine, Treatment Failure, virological failure, Health Policy, UK CHIC and UK HDRD Steering Committees, Virological failure, 3. Good health, Antiretroviral therapy, Patient benefit, Infectious Diseases, Female, medicine.symptom, Life Sciences & Biomedicine, Viral load, Cart, medicine.medical_specialty, Anti-HIV Agents, Short Communication, antiretroviral therapy, CD4 count, Asymptomatic, 03 medical and health sciences, HIV-INFECTION, Virology, Internal medicine, Drug Resistance, Viral, medicine, Humans, Science & Technology, business.industry, HIV resistance, 1103 Clinical Sciences, 030112 virology, CD4 Lymphocyte Count, Immunology, Mutation, business
Abstract

Objectives No randomized controlled trials have yet reported an individual patient benefit of initiating combination antiretroviral therapy (cART) at CD4 counts > 350 cells/μL. It is hypothesized that earlier initiation of cART in asymptomatic and otherwise healthy individuals may lead to poorer adherence and subsequently higher rates of resistance development. Methods In a large cohort of HIV-positive individuals, we investigated the emergence of new resistance mutations upon virological treatment failure according to the CD4 count at the initiation of cART. Results Of 7918 included individuals, 6514 (82.3%), 996 (12.6%) and 408 (5.2%) started cART with a CD4 count ≤ 350, 351–499 and ≥ 500 cells/μL, respectively. Virological rebound occurred while on cART in 488 (7.5%), 46 (4.6%) and 30 (7.4%) with a baseline CD4 count ≤ 350, 351–499 and ≥ 500 cells/μL, respectively. Only four (13.0%) individuals with a baseline CD4 count > 350 cells/μL in receipt of a resistance test at viral load rebound were found to have developed new resistance mutations. This compared to 107 (41.2%) of those with virological failure who had initiated cART with a CD4 count

Published
2015

12. Virological outcomes of boosted protease inhibitor-based first-line ART in subjects harbouring thymidine analogue-associated mutations as the sole form of transmitted drug resistance.

Author

Geretti, Anna Maria, White, Ellen, Orkin, Chloe, Tostevin, Anna, Tilston, Peter, Chadwick, David, Leen, Clifford, Sabin, Caroline, Dunn, David T, and UK HIV Drug Resistance Database and UK CHIC Study

Subjects
THYMIDINE, LAMIVUDINE, EFAVIRENZ, VIROLOGY, VIREMIA, TENOFOVIR
Abstract

Objectives: In subjects with transmitted thymidine analogue mutations (TAMs), boosted PIs (PI/b) are often chosen to overcome possible resistance to the NRTI backbone. However, data to guide treatment selection are limited. Our aim was to obtain firmer guidance for clinical practice using real-world cohort data.Methods: We analysed 1710 subjects who started a PI/b in combination with tenofovir or abacavir plus emtricitabine or lamivudine, and compared their virological outcomes with those of 4889 patients who started an NNRTI (predominantly efavirenz), according to the presence of ≥1 TAM as the sole form of transmitted drug resistance.Results: Participants with ≥1 TAM comprised predominantly MSM (213 of 269, 79.2%), subjects of white ethnicity (206 of 269, 76.6%) and HIV-1 subtype B infections (234 of 269, 87.0%). Most (203 of 269, 75.5%) had singleton TAMs, commonly a revertant of T215Y or T215F (112 of 269, 41.6%). Over a median of 2.5 years of follow-up, 834 of 6599 (12.6%) subjects experienced viraemia (HIV-1 RNA >50 copies/mL). The adjusted HR for viraemia was 2.17 with PI/b versus NNRTI-based therapy (95% CI 1.88-2.51; P < 0.001). Other independent predictors of viraemia included injecting drug use, black ethnicity, higher viral load and lower CD4 cell count at baseline, and receiving abacavir instead of tenofovir. Resistance showed no overall impact (adjusted HR 0.77 with ≥1 TAM versus no resistance; 95% CI 0.54-1.10; P = 0.15).Conclusions: In this cohort, patients harbouring ≥1 TAM as the sole form of transmitted drug resistance gained no apparent virological advantage from starting first-line ART with a PI/b. [ABSTRACT FROM AUTHOR]

Published
2019
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16. Low frequency of genotypic resistance in HIV-1-infected patients failing an atazanavir-containing regimen: a clinical cohort study

Author

Dolling, David I., Dunn, David T., Sutherland, Katherine A., Pillay, Deenan, Mbisa, Jean L., Parry, Chris M., Post, Frank A., Sabin, Caroline A., Cane, Patricia A., Aitken, Celia, Asboe, David, Webster, Daniel, Cane, Patricia, Castro, Hannah, Dunn, David, Dolling, David, Chadwick, David, Churchill, Duncan, Clark, Duncan, Collins, Simon, Delpech, Valerie, Geretti, Anna Maria, Goldberg, David, Hale, Antony, Hué, Stéphane, Kaye, Steve, Kellam, Paul, Lazarus, Linda, Leigh-Brown, Andrew, Mackie, Nicola, Orkin, Chloe, Rice, Philip, Phillips, Andrew, Sabin, Caroline, Smit, Erasmus, Templeton, Kate, Tilston, Peter, Tong, William, Williams, Ian, Zhang, Hongyi, Zuckerman, Mark, Greatorex, Jane, Wildfire, Adrian, O'Shea, Siobhan, Mullen, Jane, Mbisa, Tamyo, Cox, Alison, Tandy, Richard, Hale, Tony, Fawcett, Tracy, Hopkins, Mark, Ashton, Lynn, Booth, Claire, Garcia-Diaz, Ana, Shepherd, Jill, Schmid, Matthias L., Payne, Brendan, Hay, Phillip, Rice, Phillip, Paynter, Mary, Bibby, David, Kirk, Stuart, MacLean, Alasdair, Gunson, Rory, Coughlin, Kate, Fearnhill, Esther, Fradette, Lorraine, Porter, Kholoud, Ainsworth, Jonathan, Anderson, Jane, Babiker, Abdel, Fisher, Martin, Gazzard, Brian, Gilson, Richard, Gompels, Mark, Hill, Teresa, Johnson, Margaret, Kegg, Stephen, Leen, Clifford, Nelson, Mark, Palfreeman, Adrian, Post, Frank, Sachikonye, Memory, Schwenk, Achim, Walsh, John, Huntington, Susie, Jose, Sophie, Thornton, Alicia, Glabay, Adam, Orkin, C., Garrett, N., Lynch, J., Hand, J., de Souza, C., Fisher, M., Perry, N., Tilbury, S., Gazzard, B., Nelson, M., Waxman, M., Asboe, D., Mandalia, S., Delpech, V., Anderson, J., Munshi, S., Korat, H., Welch, J., Poulton, M., MacDonald, C., Gleisner, Z., Campbell, L., Gilson, R., Brima, N., Williams, I., Schwenk, A., Ainsworth, J., Wood, C., Miller, S., Johnson, M., Youle, M., Lampe, F., Smith, C., Grabowska, H., Chaloner, C., Puradiredja, D., Walsh, J., Weber, J., Ramzan, F., Mackie, N., Winston, A., Leen, C., Wilson, A., Allan, S., Palfreeman, A., Moore, A., and Wakeman, K.

Subjects
Male, Mutation rate, Pyridines, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, THERAPY, Cohort Studies, 0302 clinical medicine, HIV Protease, Mutation Rate, 1108 Medical Microbiology, Genotype, Pharmacology (medical), 030212 general & internal medicine, Pharmacology & Pharmacy, Treatment Failure, drug resistance mutations, Original Research, 0303 health sciences, virological failure, UK Collaborative HIV Cohort Study (UK CHIC), Proteolytic enzymes, virus diseases, Middle Aged, 3. Good health, Infectious Diseases, Female, 1115 Pharmacology and Pharmaceutical Sciences, Life Sciences & Biomedicine, Oligopeptides, medicine.drug, Cohort study, 0605 Microbiology, Microbiology (medical), Adult, medicine.medical_specialty, Anti-HIV Agents, Atazanavir Sulfate, protease inhibitors, Mutation, Missense, RITONAVIR, Biology, Microbiology, Medication Adherence, 03 medical and health sciences, Internal medicine, SCORE, Drug Resistance, Viral, medicine, Humans, 030304 developmental biology, Pharmacology, Science & Technology, HIV, Virology, naive patients, United States, Atazanavir, Regimen, HIV-1, Ritonavir, UK HIV Drug Resistance Database (UKHDRD)
Abstract

Author(s): Dolling, David I; Dunn, David T; Sutherland, Katherine A; Pillay, Deenan; Mbisa, Jean L; Parry, Chris M; Post, Frank A; Sabin, Caroline A; Cane, Patricia A; UK HIV Drug Resistance Database (UKHDRD); UK Collaborative HIV Cohort Study (UK CHIC) | Abstract: ObjectivesTo determine protease mutations that develop at viral failure for protease inhibitor (PI)-naive patients on a regimen containing the PI atazanavir.MethodsResistance tests on patients failing atazanavir, conducted as part of routine clinical care in a multicentre observational study, were randomly matched by subtype to resistance tests from PI-naive controls to account for natural polymorphisms. Mutations from the consensus B sequence across the protease region were analysed for association and defined using the IAS-USA 2011 classification list.ResultsFour hundred and five of 2528 (16%) patients failed therapy containing atazanavir as a first PI over a median (IQR) follow-up of 1.76 (0.84-3.15) years and 322 resistance tests were available for analysis. Recognized major atazanavir mutations were found in six atazanavir-experienced patients (P l 0.001), including I50L and N88S. The minor mutations most strongly associated with atazanavir experience were M36I, M46I, F53L, A71V, V82T and I85V (P l 0.05). Multiple novel mutations, I15S, L19T, K43T, L63P/V, K70Q, V77I and L89I/T/V, were also associated with atazanavir experience.ConclusionsViral failure on atazanavir-containing regimens was not common and major resistance mutations were rare, suggesting that adherence may be a major contributor to viral failure. Novel mutations were described that have not been previously documented.

17. The impact of different definitions on the estimated rate of transmitted HIV drug resistance in the United Kingdom.

Author

Green H, Tilston P, Fearnhill E, Pillay D, and Dunn DT

Subjects
Genotype, Humans, RNA, Viral genetics, United Kingdom, Drug Resistance, Viral, HIV drug effects, HIV Infections transmission, HIV Infections virology, Microbial Sensitivity Tests methods
Abstract

Background: The use of different lists of resistance mutations has resulted in estimates of transmitted HIV drug resistance (THDR) that are often not comparable., Methods: We estimated the rate of THDR based on the 3 definitions: > or =1 major mutation(s) listed on the International AIDS Society (IAS)-USA drug resistance mutation (DRM) 2006 list; > or =1 surveillance drug resistance mutation(s) (SDRM) on the published list by Shafer et al; and low-level/intermediate/high-level resistance to > or =1 drug(s) according to the Stanford HIVdb interpretation algorithm. Analyses were based on genotypic resistance tests conducted during 1997-2005 on antiretroviral therapy-naive patients and reported to the UK HIV Drug Resistance Database. The effect on THDR rates of revisions to the IAS-DRM list was also examined., Results: Overall, 10.0%, 9.2%, and 10.4% of the 8272 samples available for analysis were classified as having THDR by the IAS-DRM, SDRM, and Stanford definitions, respectively; however, there was discordance for 244 (3%) samples. Changes in the version of the IAS-DRM list over time resulted in 4%-7% differences in the estimated rate of THDR, which increased from 4%-5% during 1997-2000 to 5%-7% during 2001-2005., Conclusions: The choice of genotypic definition had a minor influence on the estimated rate of THDR. The SDRM list is recommended for epidemiological estimates of THDR as it has been designed with such studies in mind.

Published
2008
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