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1. 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

2. A tale of two countries: all‐cause mortality among people living with HIV and receiving combination antiretroviral therapy in the UK and Canada

Author

Patterson, S, Jose, S, Samji, H, Cescon, A, Ding, E, Zhu, J, Anderson, J, Burchell, AN, Cooper, C, Hill, T, Hull, M, Klein, MB, Loutfy, M, Martin, F, Machouf, N, Montaner, JSG, Nelson, M, Raboud, J, Rourke, SB, Tsoukas, C, Hogg, RS, Sabin, C, Kelly, Deborah, Sanche, Stephen, Wong, Alexander, Antoniou, Tony, Bayoumi, Ahmed, Nosyk, Bohdan, Cotterchio, Michelle, Goldsmith, Charlie, Guillemi, Silvia, Richard Harrigan, P., Harris, Marianne, Hosein, Sean, Johnston, Sharon, Liddy, Clare, Lima, Viviane, Moore, David, Palmer, Alexis, Phillips, Peter, Rachlis, Anita, Smieja, Marek, Trottier, Benoit, Wainberg, Mark, Walmsley, Sharon, Archibald, Chris, Clement, Ken, Doolittle‐Romas, Monique, Edmiston, Laurie, Huskins, Brian, Lawless, Jerry, Lee, Douglas, Masching, Renee, Tattle, Stephen, Zahirieh, Alireza, Allen, Claire, Calvez, Stryker, Colley, Guillaume, Chia, Jason, Corsi, Daniel, Gilbert, Louise, Gataric, Nada, Leslie, Alia, Light, Lucia, Mackie, David, Pexos, Costa, Shurgold, Susan, Szadkowski, Leah, Wong, John, Yip, Benita, Younger, Jaime, Ainsworth, Jonathan, Allan, Sris, Babiker, Abdel, Chadwick, David, Delpech, Valerie, Dunn, David, Fisher, Martin, Gazzard, Brian, Gilson, Richard, Gompels, Mark, Hay, Phillip, Johnson, Margaret, Kegg, Stephen, Leen, Clifford, Orkin, Chloe, Palfreeman, Adrian, Phillips, Andrew, Pillay, Deenan, Post, Frank, Pritchard, Jillian, Sachikonye, Memory, Schwenk, Achim, Tariq, Anjum, Walsh, John, Thornton, Alicia, Glabay, Adam, Perry, Nicky, Tilbury, Stuart, Youssef, Elaney, Churchill, Duncan, Everett, Rhiannon, Asboe, David, Mandalia, Sundhiya, Korat, Hardik, Taylor, Chris, Gleisner, Zachary, Ibrahim, Fowzia, Campbell, Lucy, Brima, Nataliya, Williams, Ian, Youle, Mike, Lampe, Fiona, Smith, Colette, Tsintas, Rob, Chaloner, Clinton, Hutchinson, Samantha, Huntington, Susie, Mackie, Nicky, Winston, Alan, Weber, Jonathan, Ramzan, Farhan, Carder, Mark, Lynch, Janet, Hand, James, de Souza, Carl, Munshi, Sajid, Miller, Sheila, Wood, Chris, Wilson, Alan, Morris, Sheila, Allan, Sue, Memon, Khurram, Lewszuk, Adam, Cope, Emma, Gibson, Jane, Main, Paul, Dhillon, Mandip, Russell‐Sharpe, Sarah, Harte, Andrew, Clay, Stephen, Spencer, Hazel, Jones, Ron, Cumming, Shirley, Atkinson, Claire, and Trevelion, Roy

Published
2017
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3. 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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4. Development and application of a new measure of engagement in out‐patient HIV care

Author

Howarth, AR, Burns, FM, Apea, V, Jose, S, Hill, T, Delpech, VC, Evans, A, Mercer, CH, Michie, S, Morris, S, Sachikonye, M, Sabin, C, Ainsworth, Jonathan, Allan, Sris, Anderson, Jane, Babiker, Abdel, Chadwick, David, Dunn, David, Fisher, Martin, Gazzard, Brian, Gilson, Richard, Gompels, Mark, Hay, Phillip, Johnson, Margaret, Kegg, Stephen, Leen, Clifford, Martin, Fabiola, Nelson, Mark, Orkin, Chloe, Palfreeman, Adrian, Phillips, Andrew, Pillay, Deenan, Post, Frank, Pritchard, Jillian, Schwenk, Achim, Tariq, Anjum, Trevelion, Roy, Walsh, John, Thornton, Alicia, Huntington, Susie, Glabay, Adam, Perry, N., Tilbury, S., Youssef, E., Churchill, D., Everett, R., Asboe, D., Mandalia, S., Korat, H., Taylor, C., Gleisner, Z., Ibrahim, F., Campbell, L., Brima, N., Williams, I., Youle, M., Lampe, F., Smith, C., Tsintas, R., Chaloner, C., Hutchinson, S., Mackie, N., Winston, A., Weber, J., Ramzan, F., Carder, M., Lynch, J., Hand, J., Souza, C., Anderson, J., Munshi, S., Miller, S., Wood, C., Leen, C., Wilson, A., Morris, S., Memon, K., Lewszuk, A., Cope, E., Gibson, J., Main, P., Mitchell, S., Hunter, M., Dhillon, M., Russell‐Sharpe, S., Harte, A., Clay, S., Tariq, A., Spencer, H., Jones, R., Cumming, S., and Atkinson, C.

Subjects
Adult, Male, patient engagement, Adolescent, HIV, HIV Infections, out‐patient care, retention measure, Middle Aged, Patient Acceptance of Health Care, United Kingdom, Cohort Studies, Interviews as Topic, Young Adult, cohort study, Ambulatory Care, Humans, Female, Original Research, Aged
Abstract

Objectives Commonly used measures of engagement in HIV care do not take into account that the frequency of attendance is related to changes in treatment and health status. This study developed a new measure of engagement in care (EIC) incorporating clinical factors. Methods We conducted semi‐structured interviews with eight HIV physicians to identify factors associated with the timing of patients' next scheduled appointments. These factors informed the development of an algorithm to classify each month of follow‐up as “in care” (on or before the time of the next expected attendance) or “out of care” (after the time of the next expected attendance). The EIC algorithm was applied to data from the UK Collaborative HIV Cohort (UK CHIC) study, a large clinical cohort study. Results The interviews indicated that time to next appointment varied depending on psychosocial and physical comorbidities, and clinical factors (time since diagnosis, AIDS diagnosis, treatment status, CD4 count and viral load). The resulting EIC algorithm was applied to 44 432 patients; 83.9% of the 3 021 224 person‐months were “in care”. Greater EIC was independently associated with older age, white ethnicity, HIV acquisition through sex between men, current use of antiretroviral therapy (ART), a higher nadir CD4 count, later calendar year and being seen at the clinic for the first time within the last year. Conclusions This algorithm describing engagement in HIV care incorporates a time‐updated measure of patients' treatment and health status. It adds to the options available for measuring this key performance indicator.

Published
2016

5. 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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6. 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

7. Incomplete Reversibility of Estimated Glomerular Filtration Rate Decline Following Tenofovir Disoproxil Fumarate Exposure

Author

Jose, Sophie, Hamzah, Lisa, Campbell, Lucy J., Hill, Teresa, Fisher, Martin, Leen, Clifford, Gilson, Richard, Walsh, John, Nelson, Mark, Hay, Phillip, Johnson, Margaret, Chadwick, David, Nitsch, Dorothea, Jones, Rachael, Sabin, Caroline A., Post, Frank A., Ainsworth, Jonathan, Anderson, Jane, Babiker, Abdel, Delpech, Valerie, Dunn, David, Gazzard, Brian, Gompels, Mark, Kegg, Stephen, Orkin, Chloe, Palfreeman, Adrian, Phillips, Andrew, Pillay, Deenan, Post, Frank, Sabin, Caroline, Sachikonye, Memory, Schwenk, Achim, Huntington, Susie, Josie, Sophie, Thornton, Alicia, Glabay, Adam, Orkin, C., Garrett, N., Lynch, J., Hand, J., de Souza, C., Fisher, M., Perry, N., Tilbury, S., Churchill, D., Gazzard, B., Nelson, M., Waxman, M., Asboe, D., Mandalia, S., Delpech, V., Anderson, J., Munshi, S., Korat, H., Poulton, M., Taylor, 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., Gompels, M., Allan, S., Palfreeman, A., Moore, A., Chadwick, D., Wakeman, K., Main, Paul, Mitchell, Hunter, and Dhillon, Mandip

Subjects
Adult, Male, eGFR slopes, kidney, Anti-HIV Agents, Adenine, renal function, Organophosphonates, HIV Infections, highly active antiretroviral therapy, Middle Aged, Viral Load, tenofovir, Drug Administration Schedule, Cohort Studies, Major Articles and Brief Reports, eGFR, HIV/AIDS, Humans, Female, Kidney Diseases, Glomerular Filtration Rate, Proportional Hazards Models
Abstract

Background. Tenofovir disoproxil fumarate (TDF) has been linked to renal impairment, but the extent to which this impairment is reversible is unclear. We aimed to investigate the reversibility of renal decline during TDF therapy. Methods. Cox proportional hazards models assessed factors associated with discontinuing TDF in those with an exposure duration of >6 months. In those who discontinued TDF therapy, linear piecewise regression models estimated glomerular filtration rate (eGFR) slopes before initiation of, during, and after discontinuation of TDF therapy. Factors associated with not achieving eGFR recovery 6 months after discontinuing TDF were assessed using multivariable logistic regression. Results. We observed declines in the eGFR during TDF exposure (mean slopes, −15.7 mL/minute/1.73 m2/year [95% confidence interval {CI}, −20.5 to −10.9] during the first 3 months and −3.1 mL/minute/1.73 m2/year [95% CI, −4.6 to −1.7] thereafter) and evidence of eGFR increases following discontinuation of TDF therapy (mean slopes, 12.5 mL/minute/1.73 m2/year [95% CI, 8.9–16.1] during the first 3 months and 0.8 mL/minute/1.73 m2/year [95% CI, .1–1.5] thereafter). Following TDF discontinuation, 38.6% of patients with a decline in the eGFR did not experience recovery. A higher eGFR at baseline, a lower eGFR after discontinuation of TDF therapy, and more-prolonged exposure to TDF were associated with an increased risk of incomplete recovery 6 months after discontinuation of TDF therapy. Conclusions. This study shows that a decline in the eGFR during TDF therapy was not fully reversible in one third of patients and suggests that prolonged TDF exposure at a low eGFR should be avoided.

Published
2014

8. Mortality of treated HIV-1 positive individuals according to viral subtype in Europe and Canada: collaborative cohort analysis

Author

Medicina i Cirurgia, Universitat Rovira i Virgili, Collaboration Observ HIV Epidemio, UK Collaborative HIV Cohort Study, Canadian Observational Cohort Coll, Antiretroviral Therapy Cohort Coll, Russell-Sharp, Sarah, Douglas, Sarah, Martin, Fabiola, Dhillon, Mandip, Hay, Phillip, Sachikonye, Memory, Hunter, Dr, Mitchell, Dr, Main, Paul, Kegg, Stephen, Lewszuk, Adam, Bojanowski, Josef, Fox, Lynn, Moore, Anne, Palfreeman, Adrian, Allan, Sue, Gompels, Mark, Morris, Sheila, Wilson, Alan, Leen, Clifford, Carder, Mark, Ramzan, Farhan, Weber, Jonathan, Winston, Alan, Mackie, Nicky, Walsh, John, Thornton, Alicia, Sabin, Caroline, Phillips, Andrew, Jose, Sophie, Huntington, Susie, Hill, Teresa, Chaloner, Clinton, Smith, Colette, Lampe, Fiona, Youle, Mike, Johnson, Margaret, Wood, Chris, Miller, Sheila, Schwenk, Achim, Ainsworth, Jonathan, Williams, Ian, Brima, Nataliya, Gilson, Richard, Gibson, Jane, Gibney, Marie, Cope, Emma, Baillie, Kirsty, Chadwick, David, Glabay, Adam, Dunn, David, Babiker, Abdel, Campbell, Lucy, Ibrahim, Fowzia, Gleisner, Zachary, Taylor, Chris, Korat, Hardik, Post, Frank, Awosika, Damilola, Munshi, Sajid, Anderson, Jane, Mandalia, Sundhiya, Asboe, David, Waxman, Matthew, Nelson, Mark, Gazzard, Brian, Churchill, Duncan, Youssef, Elaney, Tilbury, Stuart, Perry, Nicky, Fisher, Martin, de Souza, Carl, Hand, James, Lynch, Janet, Garrett, Nigel, Orkin, Chloe, Pillay, Deenan, Delpech, Valerie, Trickey, Adam, Ingle, Suzanne, May, Margaret, Sterne, Jonathan, Zangerle, Robert, Williams, M, Medicina i Cirurgia, Universitat Rovira i Virgili, Collaboration Observ HIV Epidemio, UK Collaborative HIV Cohort Study, Canadian Observational Cohort Coll, Antiretroviral Therapy Cohort Coll, Russell-Sharp, Sarah, Douglas, Sarah, Martin, Fabiola, Dhillon, Mandip, Hay, Phillip, Sachikonye, Memory, Hunter, Dr, Mitchell, Dr, Main, Paul, Kegg, Stephen, Lewszuk, Adam, Bojanowski, Josef, Fox, Lynn, Moore, Anne, Palfreeman, Adrian, Allan, Sue, Gompels, Mark, Morris, Sheila, Wilson, Alan, Leen, Clifford, Carder, Mark, Ramzan, Farhan, Weber, Jonathan, Winston, Alan, Mackie, Nicky, Walsh, John, Thornton, Alicia, Sabin, Caroline, Phillips, Andrew, Jose, Sophie, Huntington, Susie, Hill, Teresa, Chaloner, Clinton, Smith, Colette, Lampe, Fiona, Youle, Mike, Johnson, Margaret, Wood, Chris, Miller, Sheila, Schwenk, Achim, Ainsworth, Jonathan, Williams, Ian, Brima, Nataliya, Gilson, Richard, Gibson, Jane, Gibney, Marie, Cope, Emma, Baillie, Kirsty, Chadwick, David, Glabay, Adam, Dunn, David, Babiker, Abdel, Campbell, Lucy, Ibrahim, Fowzia, Gleisner, Zachary, Taylor, Chris, Korat, Hardik, Post, Frank, Awosika, Damilola, Munshi, Sajid, Anderson, Jane, Mandalia, Sundhiya, Asboe, David, Waxman, Matthew, Nelson, Mark, Gazzard, Brian, Churchill, Duncan, Youssef, Elaney, Tilbury, Stuart, Perry, Nicky, Fisher, Martin, de Souza, Carl, Hand, James, Lynch, Janet, Garrett, Nigel, Orkin, Chloe, Pillay, Deenan, Delpech, Valerie, Trickey, Adam, Ingle, Suzanne, May, Margaret, Sterne, Jonathan, Zangerle, Robert, and Williams, M

Abstract

To estimate prognosis by viral subtype in HIV-1-infected individuals from start of antiretroviral therapy (ART) and after viral failure.Collaborative analysis of data from eight European and three Canadian cohorts.Adults (N>20?000) who started triple ART between 1996 and 2012 and had data on viral subtype were followed for mortality. We estimated crude and adjusted (for age, sex, regimen, CD4 cell count, and AIDS at baseline, period of starting ART, stratified by cohort, region of origin and risk group) mortality hazard ratios (MHR) by subtype. We estimated MHR subsequent to viral failure defined as two HIV-RNA measurements greater than 500 copies/ml after achieving viral suppression.The most prevalent subtypes were B (15?419; 74%), C (2091; 10%), CRF02AG (1057; 5%), A (873; 4%), CRF01AE (506; 2.4%), G (359; 1.7%), and D (232; 1.1%). Subtypes were strongly patterned by region of origin and risk group. During 104?649 person-years of observation, 1172/20?784 patients died. Compared with subtype B, mortality was higher for subtype A, but similar for all other subtypes. MHR for A versus B were 1.13 (95% confidence interval 0.85,1.50) when stratified by cohort, increased to 1.78 (1.27,2.51) on stratification by region and risk, and attenuated to 1.59 (1.14,2.23) on adjustment for covariates. MHR for A versus B was 2.65 (1.64,4.28) and 0.95 (0.57,1.57) for patients who started ART with CD4 cell count below, or more than, 100 cells/?l, respectively. There was no difference in mortality between subtypes A, B and C after viral failure.Patients with subtype A had worse prognosis, an observation which may be confounded by socio-demographic factors.

Published
2016

9. Mortality of treated HIV-1 positive individuals according to viral subtype in Europe and Canada: collaborative cohort analysis

Author

May, Margaret T., Gill, Michael J., Wittkop, Linda, Klein, Marina, Sabin, Caroline, Harrigan, P. Richard, Dunn, David, Vehreschild, Jorg Janne, Rubio, Rafael, Mocroft, Amanda, Cavassini, Matthias, Reiss, Peter, Monforte, Antonella D'Arminio, Zangerle, Robert, Ingle, Suzanne M., Hill, Teresa, Jose, Sophie, Sterne, Jonathan A. C., Boulle, Andrew, Stephan, Christoph, Miro, Jose M., Chene, Gene-Vieve, Costagliola, Dominique, Dabis, Francois, del Amo, Julia, Van Sighem, Ard, Vehreschild, Jorg, Gill, John, Guest, Jodie, Haerry, David Hans-Ulrich, Hogg, Robert, Justice, Amy, Obel, Niels, Crane, Heidi, Smith, Colette, Saag, Michael, Sterling, Tim, Teira, Ramon, Williams, Matthew, Sterne, Jonathan, May, Margaret, Ingle, Suzanne, Trickey, Adam, Ainsworth, Jonathan, Anderson, Jane, Babiker, Abdel, Chadwick, David, Delpech, Valerie, Fisher, Martin, Gazzard, Brian, Gilson, Richard, Hay, Phillip, Gompels, Mark, Johnson, Margaret, Kegg, Stephen, Leen, Clifford, Mackie, Nicky, Nelson, Mark, Orkin, Chloe, Palfreeman, Adrian, Phillips, Andrew, Pillay, Deenan, Post, Frank, Sachikonye, Memory, Schwenk, Achim, Walsh, John, Thornton, Alicia, Huntington, Susie, Glabay, Adam, Garrett, Nigel, Lynch, Janet, Hand, James, de Souza, Carl, Perry, Nicky, Tilbury, Stuart, Youssef, Elaney, Churchill, Duncan, Waxman, Matthew, Asboe, David, Mandalia, Sundhiya, Munshi, Sajid, Awosika, Damilola, Korat, Hardik, Taylor, Chris, Gleisner, Zachary, Ibrahim, Fowzia, Campbell, Lucy, Baillie, Kirsty, Cope, Emma, Gibney, Marie, Gibson, Jane, Brima, Nataliya, Williams, Ian, Miller, Sheila, Wood, Chris, Youle, Mike, Lampe, Fiona, Chaloner, Clinton, Winston, Alan, Weber, Jonathan, Ramzan, Farhan, Carder, Mark, Wilson, Alan, Morris, Sheila, Allan, Sue, Moore, Anne, Fox, Lynn, Bojanowski, Josef, Lewszuk, Adam, Main, Paul, Mitchell, Dr, Hunter, Dr, Dhillon, Mandip, Martin, Fabiola, Douglas, Sarah, Russell-Sharp, Sarah, May, Margaret T., Gill, Michael J., Wittkop, Linda, Klein, Marina, Sabin, Caroline, Harrigan, P. Richard, Dunn, David, Vehreschild, Jorg Janne, Rubio, Rafael, Mocroft, Amanda, Cavassini, Matthias, Reiss, Peter, Monforte, Antonella D'Arminio, Zangerle, Robert, Ingle, Suzanne M., Hill, Teresa, Jose, Sophie, Sterne, Jonathan A. C., Boulle, Andrew, Stephan, Christoph, Miro, Jose M., Chene, Gene-Vieve, Costagliola, Dominique, Dabis, Francois, del Amo, Julia, Van Sighem, Ard, Vehreschild, Jorg, Gill, John, Guest, Jodie, Haerry, David Hans-Ulrich, Hogg, Robert, Justice, Amy, Obel, Niels, Crane, Heidi, Smith, Colette, Saag, Michael, Sterling, Tim, Teira, Ramon, Williams, Matthew, Sterne, Jonathan, May, Margaret, Ingle, Suzanne, Trickey, Adam, Ainsworth, Jonathan, Anderson, Jane, Babiker, Abdel, Chadwick, David, Delpech, Valerie, Fisher, Martin, Gazzard, Brian, Gilson, Richard, Hay, Phillip, Gompels, Mark, Johnson, Margaret, Kegg, Stephen, Leen, Clifford, Mackie, Nicky, Nelson, Mark, Orkin, Chloe, Palfreeman, Adrian, Phillips, Andrew, Pillay, Deenan, Post, Frank, Sachikonye, Memory, Schwenk, Achim, Walsh, John, Thornton, Alicia, Huntington, Susie, Glabay, Adam, Garrett, Nigel, Lynch, Janet, Hand, James, de Souza, Carl, Perry, Nicky, Tilbury, Stuart, Youssef, Elaney, Churchill, Duncan, Waxman, Matthew, Asboe, David, Mandalia, Sundhiya, Munshi, Sajid, Awosika, Damilola, Korat, Hardik, Taylor, Chris, Gleisner, Zachary, Ibrahim, Fowzia, Campbell, Lucy, Baillie, Kirsty, Cope, Emma, Gibney, Marie, Gibson, Jane, Brima, Nataliya, Williams, Ian, Miller, Sheila, Wood, Chris, Youle, Mike, Lampe, Fiona, Chaloner, Clinton, Winston, Alan, Weber, Jonathan, Ramzan, Farhan, Carder, Mark, Wilson, Alan, Morris, Sheila, Allan, Sue, Moore, Anne, Fox, Lynn, Bojanowski, Josef, Lewszuk, Adam, Main, Paul, Mitchell, Dr, Hunter, Dr, Dhillon, Mandip, Martin, Fabiola, Douglas, Sarah, and Russell-Sharp, Sarah

Abstract

Objectives:To estimate prognosis by viral subtype in HIV-1-infected individuals from start of antiretroviral therapy (ART) and after viral failure.Design:Collaborative analysis of data from eight European and three Canadian cohorts.Methods:Adults (N>20000) who started triple ART between 1996 and 2012 and had data on viral subtype were followed for mortality. We estimated crude and adjusted (for age, sex, regimen, CD4(+) cell count, and AIDS at baseline, period of starting ART, stratified by cohort, region of origin and risk group) mortality hazard ratios (MHR) by subtype. We estimated MHR subsequent to viral failure defined as two HIV-RNA measurements greater than 500 copies/ml after achieving viral suppression.Results:The most prevalent subtypes were B (15419; 74%), C (2091; 10%), CRF02AG (1057; 5%), A (873; 4%), CRF01AE (506; 2.4%), G (359; 1.7%), and D (232; 1.1%). Subtypes were strongly patterned by region of origin and risk group. During 104649 person-years of observation, 1172/20784 patients died. Compared with subtype B, mortality was higher for subtype A, but similar for all other subtypes. MHR for A versus B were 1.13 (95% confidence interval 0.85,1.50) when stratified by cohort, increased to 1.78 (1.27,2.51) on stratification by region and risk, and attenuated to 1.59 (1.14,2.23) on adjustment for covariates. MHR for A versus B was 2.65 (1.64,4.28) and 0.95 (0.57,1.57) for patients who started ART with CD4(+) cell count below, or more than, 100 cells/l, respectively. There was no difference in mortality between subtypes A, B and C after viral failure.Conclusion:Patients with subtype A had worse prognosis, an observation which may be confounded by socio-demographic factors. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

Published
2016

10. 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.

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