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

S Jose¹, K Quinn², D Dunn³, A Cox⁴, C Sabin¹, S Fidler²; UK CHIC and UK HDRD Steering Committees

Collaborators, Affiliations

Collaborators

UK CHIC and UK HDRD Steering Committees:
Jonathan Ainsworth, Sris Allan, Jane Anderson, Abdel Babiker, David Chadwick, Valerie Delpech, Martin Fisher, Brian Gazzard, Richard Gilson, Mark Gompels, Phillip Hay, Teresa Hill, Margaret Johnson, Stephen Kegg, Clifford Leen, Fabiola Martin, Mark Nelson, Chloe Orkin, Adrian Palfreeman, Andrew Phillips, Deenan Pillay, Frank Post, Jillian Pritchard, Memory Sachikonye, Achim Schwenk, Anjum Tariq, John Walsh, Alicia Thornton, Adam Glabay, N Perry, S Tilbury, E Youssef, D Churchill, R Everett, D Asboe, S Mandalia, H Korat, C Taylor, Z Gleisner, F Ibrahim, L Campbell, N Brima, I Williams, M Youle, F Lampe, C Smith, R Tsintas, C Chaloner, S Hutchinson, S Huntington, N Mackie, A Winston, J Weber, F Ramzan, M Carder, J Lynch, J Hand, C Souza, S Munshi, S Miller, C Wood, A Wilson, S Morris, S Allan, A Palfreeman, K Memon, A Ewszuk, D Chadwick, E Cope, J Gibson, S Kegg, P Main, Dr Mitchell, Dr Hunter, P Hay, M Dhillon, F Martin, S Russell-Sharpe, A Harte, S Clay, A Tariq, H Spencer, R Jones, C Atkinson, V Delpech, M Sachikonye, Celia Aitken, Anton Pozniak, Patricia Cane, Duncan Clark, Simon Collins, Samuel Douthwaite, Ellen White, Christophe Fraser, Anna Maria Geretti, Antony Hale, Stéphane Hué, Steve Kaye, Paul Kellam, Linda Lazarus, Andrew Leigh-Brown, Tamyo Mbisa, Samuel Moses, Eleni Nastouli, Erasmus Smit, Kate Templeton, Peter Tilston, Daniel Webster, Hongyi Zhang, Jane Greatorex, Jane Mullen, Richard Tandy, Tracy Fawcett, Mark Hopkins, Lynn Ashton, Claire Booth, Ana Garcia-Diaz, Jill Shepherd, Matthias L Schmid, Brendan Payne, Spiro Pere, Jonathan Hubb, Stuart Kirk, Rory Gunson, Amanda Bradley-Stewart

Affiliations

¹ Research Department of Infection and Population Health, UCL, London, UK.
² Department of Medicine, Imperial College London, London, UK.
³ Medical Research Council Clinical Trials Unit at UCL, London, UK.
⁴ Infection and Immunity, Imperial College Healthcare NHS Trust, London, UK.

PMID: 26306942
PMCID: PMC4949527
DOI: 10.1111/hiv.12302

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

S Jose et al. HIV Med. 2016 May.

. 2016 May;17(5):368-72.

doi: 10.1111/hiv.12302. Epub 2015 Aug 25.

Authors

S Jose¹, K Quinn², D Dunn³, A Cox⁴, C Sabin¹, S Fidler²; UK CHIC and UK HDRD Steering Committees

Collaborators

UK CHIC and UK HDRD Steering Committees:
Jonathan Ainsworth, Sris Allan, Jane Anderson, Abdel Babiker, David Chadwick, Valerie Delpech, Martin Fisher, Brian Gazzard, Richard Gilson, Mark Gompels, Phillip Hay, Teresa Hill, Margaret Johnson, Stephen Kegg, Clifford Leen, Fabiola Martin, Mark Nelson, Chloe Orkin, Adrian Palfreeman, Andrew Phillips, Deenan Pillay, Frank Post, Jillian Pritchard, Memory Sachikonye, Achim Schwenk, Anjum Tariq, John Walsh, Alicia Thornton, Adam Glabay, N Perry, S Tilbury, E Youssef, D Churchill, R Everett, D Asboe, S Mandalia, H Korat, C Taylor, Z Gleisner, F Ibrahim, L Campbell, N Brima, I Williams, M Youle, F Lampe, C Smith, R Tsintas, C Chaloner, S Hutchinson, S Huntington, N Mackie, A Winston, J Weber, F Ramzan, M Carder, J Lynch, J Hand, C Souza, S Munshi, S Miller, C Wood, A Wilson, S Morris, S Allan, A Palfreeman, K Memon, A Ewszuk, D Chadwick, E Cope, J Gibson, S Kegg, P Main, Dr Mitchell, Dr Hunter, P Hay, M Dhillon, F Martin, S Russell-Sharpe, A Harte, S Clay, A Tariq, H Spencer, R Jones, C Atkinson, V Delpech, M Sachikonye, Celia Aitken, Anton Pozniak, Patricia Cane, Duncan Clark, Simon Collins, Samuel Douthwaite, Ellen White, Christophe Fraser, Anna Maria Geretti, Antony Hale, Stéphane Hué, Steve Kaye, Paul Kellam, Linda Lazarus, Andrew Leigh-Brown, Tamyo Mbisa, Samuel Moses, Eleni Nastouli, Erasmus Smit, Kate Templeton, Peter Tilston, Daniel Webster, Hongyi Zhang, Jane Greatorex, Jane Mullen, Richard Tandy, Tracy Fawcett, Mark Hopkins, Lynn Ashton, Claire Booth, Ana Garcia-Diaz, Jill Shepherd, Matthias L Schmid, Brendan Payne, Spiro Pere, Jonathan Hubb, Stuart Kirk, Rory Gunson, Amanda Bradley-Stewart

Affiliations

¹ Research Department of Infection and Population Health, UCL, London, UK.
² Department of Medicine, Imperial College London, London, UK.
³ Medical Research Council Clinical Trials Unit at UCL, London, UK.
⁴ Infection and Immunity, Imperial College Healthcare NHS Trust, London, UK.

PMID: 26306942
PMCID: PMC4949527
DOI: 10.1111/hiv.12302

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.

Keywords: CD4 count; HIV resistance; antiretroviral therapy; virological failure.

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References

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

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

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