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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. COVID-19 due to the B.1.617.2 (Delta) variant compared to B.1.1.7 (Alpha) variant of SARS-CoV-2: a prospective observational cohort study

Author

Kläser, Kerstin, Molteni, Erika, Graham, Mark, Canas, Liane S., Österdahl, Marc F., Antonelli, Michela, Chen, Liyuan, Deng, Jie, Murray, Benjamin, Kerfoot, Eric, Wolf, Jonathan, May, Anna, Fox, Ben, Capdevila, Joan, Aanensen, David M., Abudahab, Khalil, Adams, Helen, Adams, Alexander, Afifi, Safiah, Aggarwal, Dinesh, Ahmad, Shazaad S. Y., Aigrain, Louise, Alcolea-Medina, Adela, Alikhan, Nabil-Fareed, Allara, Elias, Amato, Roberto, Angyal, Adrienn, Annett, Tara, Aplin, Stephen, Ariani, Cristina V., Asad, Hibo, Ash, Amy, Ashfield, Paula, Ashford, Fiona, Atkinson, Laura, Attwood, Stephen W., Auckland, Cressida, Aydin, Alp, Baker, David J., Baker, Paul, Balcazar, Carlos E., Ball, Jonathan, Barrett, Jeffrey C., Barrow, Magdalena, Barton, Edward, Bashton, Matthew, Bassett, Andrew R., Batra, Rahul, Baxter, Chris, Bayzid, Nadua, Beaver, Charlotte, Beckett, Angela H., Beckwith, Shaun M., Bedford, Luke, Beer, Robert, Beggs, Andrew, Bellis, Katherine L., Berry, Louise, Bertolusso, Beatrice, Best, Angus, Betteridge, Emma, Bibby, David, Bicknell, Kelly, Binns, Debbie, Birchley, Alec, Bird, Paul W., Bishop, Chloe, Blacow, Rachel, Blakey, Victoria, Blane, Beth, Bolt, Frances, Bonfield, James, Bonner, Stephen, Bonsall, David, Boswell, Tim, Bosworth, Andrew, Bourgeois, Yann, Boyd, Olivia, Bradley, Declan T., Breen, Cassie, Bresner, Catherine, Breuer, Judith, Bridgett, Stephen, Bronner, Iraad F., Brooks, Ellena, Broos, Alice, Brown, Julianne R., Bucca, Giselda, Buchan, Sarah L., Buck, David, Bull, Matthew, Burns, Phillipa J., Burton-Fanning, Shirelle, Byaruhanga, Timothy, Byott, Matthew, Campbell, Sharon, Carabelli, Alessandro M., Cargill, James S., Carlile, Matthew, Carvalho, Sílvia F., Casey, Anna, Castigador, Anibolina, Catalan, Jana, Chalker, Vicki, Chaloner, Nicola J., Chand, Meera, Chappell, Joseph G., Charalampous, Themoula, Chatterton, Wendy, Chaudhry, Yasmin, Churcher, Carol M., Clark, Gemma, Clarke, Phillip, Cogger, Benjamin J., Cole, Kevin, Collins, Jennifer, Colquhoun, Rachel, Connor, Thomas R., Cook, Kate F., Coombes, Jason, Corden, Sally, Cormie, Claire, Cortes, Nicholas, Cotic, Marius, Cotton, Seb, Cottrell, Simon, Coupland, Lindsay, Cox, MacGregor, Cox, Alison, Craine, Noel, Crawford, Liam, Cross, Aidan, Crown, Matthew, Crudgington, Dorian, Cumley, Nicola, Curran, Tanya, Curran, Martin D., da Silva Filipe, Ana, Dabrera, Gavin, Darby, Alistair C., Davidson, Rose K., Davies, Alisha, Davies, Robert M., Davis, Thomas, de Angelis, Daniela, De Lacy, Elen, de Oliveira Martins, Leonardo, de Silva, Thushan I., Debebe, Johnny, Denton-Smith, Rebecca, Dervisevic, Samir, Dewar, Rebecca, Dey, Jayasree, Dias, Joana, Dobie, Donald, Dorman, Matthew J., Downing, Fatima, Driscoll, Megan, du Plessis, Louis, Duckworth, Nichola, Durham, Jillian, Eastick, Kirstine, Easton, Lisa J., Eccles, Richard, Edgeworth, Jonathan, Edwards, Sue, Bouzidi, Kate El, Eldirdiri, Sahar, Ellaby, Nicholas, Elliott, Scott, Eltringham, Gary, Ensell, Leah, Erkiert, Michelle J., Zamudio, Marina Escalera, Essex, Sarah, Evans, Johnathan M., Evans, Cariad, Everson, William, Fairley, Derek J., Fallon, Karlie, Fanaie, Arezou, Farr, Ben W., Fearn, Christopher, Feltwell, Theresa, Ferguson, Lynne, Fina, Laia, Flaviani, Flavia, Fleming, Vicki M., Forrest, Sally, Foster-Nyarko, Ebenezer, Foulkes, Benjamin H., Foulser, Luke, Fragakis, Mireille, Frampton, Dan, Francois, Sarah, Fraser, Christophe, Freeman, Timothy M., Fryer, Helen, Fuchs, Marc, Fuller, William, Gajee, Kavitha, Galai, Katerina, Gallagher, Abbie, Gallagher, Eileen, Gallagher, Michael D., Gallis, Marta, Gaskin, Amy, Gatica-Wilcox, Bree, Geidelberg, Lily, Gemmell, Matthew, Georgana, Iliana, George, Ryan P., Gifford, Laura, Gilbert, Lauren, Girgis, Sophia T., Glaysher, Sharon, Goldstein, Emily J., Golubchik, Tanya, Gomes, Andrea N., Gonçalves, Sónia, Goodfellow, Ian G., Goodwin, Scott, Goudarzi, Salman, Gourtovaia, Marina, Graham, Clive, Graham, Lee, Grant, Paul R., Green, Luke R., Green, Angie, Greenaway, Jane, Gregory, Richard, Guest, Martyn, Gunson, Rory N., Gupta, Ravi K., Gutierrez, Bernardo, Haldenby, Sam T., Hamilton, William L., Hansford, Samantha E., Haque, Tanzina, Harris, Kathryn A., Harrison, Ian, Harrison, Ewan M., Hart, Jennifer, Hartley, John A., Harvey, William T., Harvey, Matthew, Hassan-Ibrahim, Mohammed O., Heaney, Judith, Helmer, Thomas, Henderson, John, Hesketh, Andrew R., Hey, Jessica, Heyburn, David, Higginson, Ellen E., Hill, Verity, Hill, Jack D., Hilson, Rachel A., Hilvers, Ember, Holden, Matthew T. G., Hollis, Amy, Holmes, Christopher W., Holmes, Nadine, Holmes, Alison H., Hopes, Richard, Hornsby, Hailey R., Hosmillo, Myra, Houlihan, Catherine, Howson-Wells, Hannah C., Hsu, Sharon N., Hubb, Jonathan, Huckson, Hannah, Hughes, Warwick, Hughes, Joseph, Hughes, Margaret, Hutchings, Stephanie, Idle, Giles, Illingworth, Chris J., Impey, Robert, Irish-Tavares, Dianne, Iturriza-Gomara, Miren, Izuagbe, Rhys, Jackson, Chris, Jackson, Ben, Jackson, Leigh M., Jackson, Kathryn A., Jackson, David K., Jahun, Aminu S., James, Victoria, James, Keith, Jeanes, Christopher, Jeffries, Aaron R., Jeremiah, Sarah, Jermy, Andrew, John, Michaela, Johnson, Rob, Johnson, Kate, Johnston, Ian, Jones, Owen, Jones, Sophie, Jones, Hannah, Jones, Christopher R., Jones, Neil, Joseph, Amelia, Judges, Sarah, Kay, Gemma L., Kay, Sally, Keatley, Jon-Paul, Keeley, Alexander J., Kenyon, Anita, Kermack, Leanne M., Khakh, Manjinder, Kidd, Stephen P., Kimuli, Maimuna, Kirk, Stuart, Kitchen, Christine, Kitchman, Katie, Knight, Bridget A., Koshy, Cherian, Kraemer, Moritz U. G., Kumziene-Summerhayes, Sara, Kwiatkowski, Dominic, Lackenby, Angie, Laing, Kenneth G., Lampejo, Temi, Langford, Cordelia F., Lavin, Deborah, Lawton, Andrew I., Lee, Jack C. D., Lee, David, Lensing, Stefanie V., Leonard, Steven, Levett, Lisa J., Le-Viet, Thanh, Lewis, Jonathan, Lewis, Kevin, Liddle, Jennifier, Liggett, Steven, Lillie, Patrick J., Lindsey, Benjamin B., Lister, Michelle M., Livett, Rich, Lo, Stephanie, Loman, Nicholas J., Loose, Matthew W., Louka, Stavroula F., Loveson, Katie F., Lowdon, Sarah, Lowe, Hannah, Lowe, Helen L., Lucaci, Anita O., Ludden, Catherine, Lynch, Jessica, Lyons, Ronan A., Lythgoe, Katrina, Machin, Nicholas W., MacIntyre-Cockett, George, Mack, Andrew, Macklin, Ben, Maclean, Alasdair, Macnaughton, Emily, Madona, Pinglawathee, Maes, Mailis, Maftei, Laurentiu, Mahanama, Adhyana I. K., Mahungu, Tabitha W., Mair, Daniel, Maksimovic, Joshua, Malone, Cassandra S., Maloney, Daniel, Manesis, Nikos, Manley, Robin, Mantzouratou, Anna, Marchbank, Angela, Mariappan, Arun, Martincorena, Inigo, Nunez, Rocio T. Martinez, Mather, Alison E., Maxwell, Patrick, Mayhew, Megan, Mbisa, Tamyo, McCann, Clare, McCarthy, Shane A., McCluggage, Kathryn, McClure, Patrick C., McCrone, J. T., McHugh, Martin P., McKenna, James P., McKerr, Caoimhe, McManus, Georgina M., McMurray, Claire L., McMurray, Claire, McNally, Alan, Meadows, Lizzie, Medd, Nathan, Megram, Oliver, Menegazzo, Mirko, Merrick, Ian, Michell, Stephen L., Michelsen, Michelle L., Mirfenderesky, Mariyam, Mirza, Jeremy, Miskelly, Julia, Moles-Garcia, Emma, Moll, Robin J., Molnar, Zoltan, Monahan, Irene M., Mondani, Matteo, Mookerjee, Siddharth, Moore, Christopher, Moore, Jonathan, Moore, Nathan, Moore, Catherine, Morcrette, Helen, Morgan, Sian, Morgan, Mari, Mori, Matilde, Morriss, Arthur, Moses, Samuel, Mower, Craig, Muir, Peter, Mukaddas, Afrida, Munemo, Florence, Munn, Robert, Murray, Abigail, Murray, Leanne J., Murray, Darren R., Mutingwende, Manasa, Myers, Richard, Nastouli, Eleni, Nebbia, Gaia, Nelson, Andrew, Nelson, Charlotte, Nicholls, Sam, Nichols, Jenna, Nicodemi, Roberto, Nomikou, Kyriaki, O’Grady, Justin, O’Brien, Sarah, Odedra, Mina, Ohemeng-Kumi, Natasha, Oliver, Karen, Orton, Richard J., Osman, Husam, O’Toole, Áine, Pacchiarini, Nicole, Padgett, Debra, Page, Andrew J., Park, Emily J., Park, Naomi R., Parker, Matthew D., Parmar, Surendra, Partridge, David G., Pascall, David, Patel, Amita, Patel, Bindi, Paterson, Steve, Payne, Brendan A. I., Peacock, Sharon J., Pearson, Clare, Pelosi, Emanuela, Percival, Benita, Perkins, Jon, Perry, Malorie, Pinckert, Malte L., Platt, Steven, Podplomyk, Olga, Pohare, Manoj, Pond, Marcus, Pope, Cassie F., Poplawski, Radoslaw, Powell, Jessica, Poyner, Jennifer, Prestwood, Liam, Price, Anna, Price, James R., Prieto, Jacqui A., Pritchard, David T., Prosolek, Sophie J., Pugh, Georgia, Pusok, Monika, Pybus, Oliver G., Pymont, Hannah M., Quail, Michael A., Quick, Joshua, Radulescu, Clara, Raghwani, Jayna, Ragonnet-Cronin, Manon, Rainbow, Lucille, Rajan, Diana, Rajatileka, Shavanthi, Ramadan, Newara A., Rambaut, Andrew, Ramble, John, Randell, Paul A., Randell, Paul, Ratcliffe, Liz, Raviprakash, Veena, Raza, Mohammad, Redshaw, Nicholas M., Rey, Sara, Reynolds, Nicola, Richter, Alex, Robertson, David L., Robinson, Esther, Robson, Samuel C., Rogan, Fiona, Rooke, Stefan, Rowe, Will, Roy, Sunando, Rudder, Steven, Ruis, Chris, Rushton, Steven, Ryan, Felicity, Saeed, Kordo, Samaraweera, Buddhini, Sambles, Christine M., Sanderson, Roy, Sanderson, Theo, Sang, Fei, Sass, Thea, Scher, Emily, Scott, Garren, Scott, Carol, Sehmi, Jasveen, Shaaban, Sharif, Shah, Divya, Shaw, Jessica, Shelest, Ekaterina, Shepherd, James G., Sheridan, Liz A., Sheriff, Nicola, Shirley, Lesley, Sillitoe, John, Silviera, Siona, Simpson, David A., Singh, Aditi, Singleton, Dawn, Skvortsov, Timofey, Sloan, Tim J., Sluga, Graciela, Smith, Ken, Smith, Kim S., Smith, Perminder, Smith, Darren, Smith, Louise, Smith, Colin P., Smith, Nikki, Smollett, Katherine L., Snell, Luke B., Somassa, Thomas, Southgate, Joel, Spellman, Karla, Chapman, Michael H. Spencer, Spurgin, Lewis G., Spyer, Moira J., Stanley, Rachael, Stanley, William, Stanton, Thomas D., Starinskij, Igor, Stockton, Joanne, Stonehouse, Susanne, Storey, Nathaniel, Studholme, David J., Sudhanva, Malur, Swindells, Emma, Taha, Yusri, Tan, Ngee Keong, Tang, Julian W., Tang, Miao, Taylor, Ben E. W., Taylor, Joshua F., Taylor, Sarah, Temperton, Ben, Templeton, Kate E., Thomas, Claire, Thomson, Laura, Thomson, Emma C., Thornton, Alicia, Thurston, Scott A. J., Todd, John A., Tomb, Rachael, Tong, Lily, Tonkin-Hill, Gerry, Torok, M. Estee, Tovar-Corona, Jaime M., Trebes, Amy, Trotter, Alexander J., Tsatsani, Ioulia, Turnbull, Robyn, Turtle, Lance, Twohig, Katherine A., Umpleby, Helen, Underwood, Anthony P., Vamos, Edith E., Vasylyeva, Tetyana I., Vattipally, Sreenu, Vernet, Gabrielle, Vipond, Barry B., Volz, Erik M., Walsh, Sarah, Wang, Dennis, Warne, Ben, Warwick-Dugdale, Joanna, Wastnedge, Elizabeth, Watkins, Joanne, Watson, Louisa K., Waugh, Sheila, Webster, Hermione J., Weldon, Danni, Westwick, Elaine, Whalley, Thomas, Wheeler, Helen, Whitehead, Mark, Whiteley, Max, Whitwham, Andrew, Wierzbicki, Claudia, Willford, Nicholas J., Williams, Lesley-Anne, Williams, Rebecca, Williams, Cheryl, Williams, Chris, Williams, Charlotte A., Williams, Rachel J., Williams, Thomas, Williams, Catryn, Williamson, Kathleen A., Wilson-Davies, Eleri, Witele, Eric, Withell, Karen T., Witney, Adam A., Wolverson, Paige, Wong, Nick, Workman, Trudy, Wright, Victoria, Wright, Derek W., Wyatt, Tim, Wyllie, Sarah, Xu-McCrae, Li, Yavus, Mehmet, Yaze, Geraldine, Yeats, Corin A., Yebra, Gonzalo, Yew, Wen Chyin, Young, Greg, Young, Jamie, Zarebski, Alex E., Zhang, Peijun, Modat, Marc, Hammers, Alexander, Spector, Tim D., Steves, Claire J., Sudre, Carole H., Ourselin, Sebastien, Duncan, Emma L., Radiology and nuclear medicine, Peacock, Sharon [0000-0002-1718-2782], and Apollo - University of Cambridge Repository

Subjects
B900, Adult, Multidisciplinary, SARS-CoV-2, SARS-CoV-2/genetics, Reinfection, B100, COVID-19, Humans, C500, Prospective Studies, Hepatitis D, COVID-19/epidemiology
Abstract

The Delta (B.1.617.2) variant was the predominant UK circulating SARS-CoV-2 strain between May and December 2021. How Delta infection compares with previous variants is unknown. This prospective observational cohort study assessed symptomatic adults participating in the app-based COVID Symptom Study who tested positive for SARS-CoV-2 from May 26 to July 1, 2021 (Delta overwhelmingly the predominant circulating UK variant), compared (1:1, age- and sex-matched) with individuals presenting from December 28, 2020 to May 6, 2021 (Alpha (B.1.1.7) the predominant variant). We assessed illness (symptoms, duration, presentation to hospital) during Alpha- and Delta-predominant timeframes; and transmission, reinfection, and vaccine effectiveness during the Delta-predominant period. 3581 individuals (aged 18 to 100 years) from each timeframe were assessed. The seven most frequent symptoms were common to both variants. Within the first 28 days of illness, some symptoms were more common with Delta versus Alpha infection (including fever, sore throat, and headache) and some vice versa (dyspnoea). Symptom burden in the first week was higher with Delta versus Alpha infection; however, the odds of any given symptom lasting ≥ 7 days was either lower or unchanged. Illness duration ≥ 28 days was lower with Delta versus Alpha infection, though unchanged in unvaccinated individuals. Hospitalisation for COVID-19 was unchanged. The Delta variant appeared more (1.49) transmissible than Alpha. Re-infections were low in all UK regions. Vaccination markedly reduced the risk of Delta infection (by 69-84%). We conclude that COVID-19 from Delta or Alpha infections is similar. The Delta variant is more transmissible than Alpha; however, current vaccines showed good efficacy against disease. This research framework can be useful for future comparisons with new emerging variants.

Published
2022
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3. Hepatitis B, hepatitis C, and mortality among HIV-positive individuals

Author

Thornton, Alicia C., Jose, Sophie, Bhagani, Sanjay, Chadwick, David, Dunn, David, Gilson, Richard, Main, Janice, Nelson, Mark, Rodger, Alison, Taylor, Chris, Youssef, Elaney, Leen, Clifford, Gompels, Mark, Kegg, Stephen, Schwenk, Achim, and Sabin, Caroline

Subjects
Adult, Male, Epidemiology and Social, virus diseases, HIV Infections, Hepatitis B, mortality, Hepatitis C, coinfection, United Kingdom, Cohort Studies, cohort study, Humans, Female
Abstract

Objectives: To compare rates of all-cause, liver-related, and AIDS-related mortality among individuals who are HIV-monoinfected with those coinfected with HIV and hepatitis B (HBV) and/or hepatitis C (HCV) viruses. Design: An ongoing observational cohort study collating routinely collected clinical data on HIV-positive individuals attending for care at HIV treatment centres throughout the United Kingdom. Methods: Individuals were included if they had been seen for care from 2004 onwards and had tested for HBV and HCV. Crude mortality rates (all cause, liver related, and AIDS related) were calculated among HIV-monoinfected individuals and those coinfected with HIV, HBV, and/or HCV. Poisson regression was used to adjust for confounding factors, identify independent predictors of mortality, and estimate the impact of hepatitis coinfection on mortality in this cohort. Results: Among 25 486 HIV-positive individuals, with a median follow-up 4.5 years, HBV coinfection was significantly associated with increased all-cause and liver-related mortality in multivariable analyses: adjusted rate ratios (ARR) [95% confidence intervals (95% CI)] were 1.60 (1.28–2.00) and 10.42 (5.78–18.80), respectively. HCV coinfection was significantly associated with increased all-cause (ARR 1.43, 95% CI 1.15–1.76) and liver-related mortality (ARR 6.20, 95% CI 3.31–11.60). Neither HBV nor HCV coinfection were associated with increased AIDS-related mortality: ARRs (95% CI) 1.07 (0.63–1.83) and 0.40 (0.20–0.81), respectively. Conclusion: The increased rate of all-cause and liver-related mortality among hepatitis-coinfected individuals in this HIV-positive cohort highlights the need for primary prevention and access to effective hepatitis treatment for HIV-positive individuals.

Published
2017

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. Chronic Hepatitis B and C Virus Infection and Risk for Non-Hodgkin Lymphoma in HIV-Infected Patients: A Cohort Study

Author

Wang, Qing, De Luca, Andrea, Smith, Colette, Zangerle, Robert, Sambatakou, Helen, Bonnet, Fabrice, Smit, Colette, Schommers, Philipp, Thornton, Alicia, Berenguer, Juan, Peters, Lars, Spagnuolo, Vincenzo, Ammassari, Adriana, Antinori, Andrea, Roldan, Eugenia Quiros, Mussini, Cristina, Miro, Jose M., Konopnicki, Deborah, Fehr, Jan, Campbell, Maria A., Termote, Monique, Bucher, Heiner C., De Wit, Stéphane, Costagliola, Dominique, D'Arminio-Monforte, Antonella, Castagna, Antonella, Del Amo, Julia, Mocroft, Amanda, Raben, Dorthe, Chêne, Geneviève, Touloumi, Giota, Warszawski, Josiane, Meyer, Laurence, Dabis, François, Krause, Murielle Mary, Ghosn, Jade, Leport, Catherine, Wittkop, Linda, Reiss, Peter, Wit, Ferdinand, Prins, Maria, Sabin, Caroline, Gibb, Diana, Fätkenheuer, Gerd, Obel, Niels, Thorne, Claire, Kirk, Ole, Stephan, Christoph, Pérez-Hoyos, Santiago, Hamouda, Osamah, Bartmeyer, Barbara, Chkhartishvili, Nikoloz, Noguera-Julian, Antoni, D'Arminio Monforte, Antonella, Brockmeyer, Norbert, Prieto, Luis, Conejo, Pablo Rojo, Soriano-Arandes, Antoni, Battegay, Manuel, Rauch, Andri, Tookey, Pat, Casabona, Jordi, Goetghebuer, Tessa, Sönnerborg, Anders, Torti, Carlo, Teira, Ramon, Garrido, Myriam, Haerry, David, Bohlius, Julia, Bouteloup, Vincent, Cozzi-Lepri, Alessandro, Davies, Mary-Anne, Dorrucci, Maria, Dunn, David, Egger, Matthias, Furrer, Hansjakob, Guiguet, Marguerite, Grabar, Sophie, Judd, Ali, Lambotte, Olivier, Leroy, Valériane, Lodi, Sara, Matheron, Sophie, Monge, Susana, Nakagawa, Fumiyo, Paredes, Roger, Phillips, Andrew, Puoti, Massimo, Schomaker, Michael, Sterne, Jonathan, Thiebaut, Rodolphe, Van Der Valk, Marc, Wyss, Natasha, Barger, Diana, Schwimmer, Christine, Friis-Møller, Nina, Kjaer, Jesper, Brandt, Rikke Salbøl, Wang, Q, De Luca, A, Smith, C, Zangerle, R, Sambatakou, H, Bonnet, F, Smit, C, Schommers, P, Thornton, A, Berenguer, J, Peters, L, Spagnuolo, V, Ammassari, A, Antinori, A, Roldan, E, Mussini, C, Miro, J, Konopnicki, D, Fehr, J, Campbell, M, Termote, M, Bucher, H, Puoti, M, University of Zurich, Bucher, Heiner C, Quiros Roldan, E, Miro, Jm, Campbell, Ma, Bucher, Hc, on behalf of The Hepatitis Coinfection and Non Hodgkin Lymphoma project team for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in, Eurocoord, and Castagna, Antonella

Subjects
Male, Lymphoma, Hepatitis B Surface Antigen, HIV Infections, medicine.disease_cause, Cohort Studies, 10234 Clinic for Infectious Diseases, 0302 clinical medicine, Risk Factors, HIV Infection, 030212 general & internal medicine, Viral, Chronic, media_common, Incidence (epidemiology), Hepatitis B Core Antigen, Lymphoma, Non-Hodgkin, Hazard ratio, virus diseases, General Medicine, Hepatitis C, Hepatitis B, Hepatitis B Core Antigens, Hepatitis Antibodie, 030220 oncology & carcinogenesis, RNA, Viral, Female, hepatitis c and b, Cohort study, Human, Adult, medicine.medical_specialty, Anti-HIV Agents, Biomarkers, Hepatitis Antibodies, Hepatitis B Surface Antigens, Hepatitis B, Chronic, Hepatitis C, Chronic, Humans, Immunoglobulin G, Hepatitis C virus, Non-Hodgkin, 610 Medicine & health, Settore MED/17 - MALATTIE INFETTIVE, 03 medical and health sciences, Internal medicine, Internal Medicine, medicine, media_common.cataloged_instance, HIV HCV NHL HBV, European union, Hepatitis B virus, business.industry, Risk Factor, Anti-HIV Agent, Biomarker, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), medicine.disease, digestive system diseases, 2724 Internal Medicine, Immunology, RNA, Cohort Studie, business
Abstract

Background: Non-Hodgkin lymphoma (NHL) is the most common AIDS-defining condition in the era of antiretroviral therapy (ART). Whether chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection promote NHL in HIV-infected patients is unclear. Objective: To investigate whether chronic HBV and HCV infection are associated with increased incidence of NHL in HIV-infected patients. Design: Cohort study. Setting: 18 of 33 cohorts from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). Patients: HIV-infected patients with information on HBV surface antigen measurements and detectable HCV RNA, or a positive HCV antibody test result if HCV RNA measurements were not available. Measurements: Time-dependent Cox models to assess risk for NHL in treatment-naive patients and those initiating ART, with inverse probability weighting to control for informative censoring. Results: A total of 52 479 treatment-naive patients (1339 [2.6%] with chronic HBV infection and 7506 [14.3%] with HCV infection) were included, of whom 40 219 (77%) later started ART. The median follow-up was 13 months for treatment-naive patients and 50 months for those receiving ART. A total of 252 treatment-naive patients and 310 treated patients developed NHL, with incidence rates of 219 and 168 cases per 100 000 person-years, respectively. The hazard ratios for NHL with HBV and HCV infection were 1.33 (95% CI, 0.69 to 2.56) and 0.67 (CI, 0.40 to 1.12), respectively, in treatment-naive patients and 1.74 (CI, 1.08 to 2.82) and 1.73 (CI, 1.21 to 2.46), respectively, in treated patients. Limitation: Many treatment-naive patients later initiated ART, which limited the study of the associations of chronic HBV and HCV infection with NHL in this patient group. Conclusion: In HIV-infected patients receiving ART, chronic co-infection with HBV and HCV is associated with an increased risk for NHL. Primary Funding Source: European Union Seventh Framework Programme.

Published
2017

6. 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

7. 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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