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

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

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

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 < 350 cells/μL. Conclusions: We found no evidence of increased rates of resistance development when cART was initiated at CD4 counts above 350 cells/μL. HIV Medicine

Original languageEnglish
Pages (from-to)368-372
Number of pages5
JournalHIV Medicine
Volume17
Issue number5
DOIs
Publication statusPublished - 1 May 2016

Keywords

  • Antiretroviral therapy
  • CD4 count
  • HIV resistance
  • Virological failure

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