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

Sophie Jose; K. Quinn; David Dunn; A. Cox; C. Sabin; S. Fidler; M. Fisher; B. Gazzard; R. Gilson; Mark Gompels; Phillip Hay; M. Johnson; Stephen Kegg; Clifford Leen; Fabiola Martin; M. Nelson; Adrian Palfreeman; Frank Post; Jillian Pritchard; Memory Sachikonye; Achim 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; R. Jones; C. Atkinson

doi:10.1111/hiv.12302

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

Sophie Jose, K. Quinn, David Dunn, A. Cox, C. Sabin, S. Fidler, M. Fisher, B. Gazzard, R. Gilson, Mark Gompels, Phillip Hay, M. Johnson, Stephen Kegg, Clifford Leen, Fabiola Martin, M. 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, R. Jones, C. Atkinson

Research output: Contribution to journal › Article › peer-review

5 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.

Original language	English
Pages (from-to)	368-372
Number of pages	5
Journal	HIV Medicine
Volume	17
Issue number	5
DOIs	https://doi.org/10.1111/hiv.12302
Publication status	Published - 1 May 2016
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2016 British HIV Association.

Keywords

Antiretroviral therapy
CD4 count
HIV resistance
Virological failure

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1111/hiv.12302

Cite this

Jose, S., Quinn, K., Dunn, D., Cox, A., Sabin, C., Fidler, S., Fisher, M., Gazzard, B., Gilson, R., Gompels, M., Hay, P., Johnson, M., Kegg, S., Leen, C., Martin, F., Nelson, M., Palfreeman, A., Post, F., Pritchard, J., ... Atkinson, C. (2016). Virological failure and development of new resistance mutations according to CD4 count at combination antiretroviral therapy initiation. HIV Medicine, 17(5), 368-372. https://doi.org/10.1111/hiv.12302

@article{b6a32857703c4a8d9483712e41c00c7e,

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

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 = "Antiretroviral therapy, CD4 count, HIV resistance, Virological failure",

author = "Sophie Jose and K. Quinn and David Dunn and A. Cox and C. Sabin and S. Fidler and M. Fisher and B. Gazzard and R. Gilson and Mark Gompels and Phillip Hay and M. Johnson and Stephen Kegg and Clifford Leen and Fabiola Martin and M. Nelson and Adrian Palfreeman and Frank Post and Jillian Pritchard and Memory Sachikonye and Achim Schwenk and Anjum Tariq and John Walsh and Teresa Hill and Sophie Jose and Andrew Phillips and Caroline Sabin and Alicia Thornton and David Dunn and Adam Glabay and M. Fisher and N. Perry and S. Tilbury and E. Youssef and D. Churchill and B. Gazzard and M. Nelson and R. Everett and D. Asboe and S. Mandalia and F. Post and H. Korat and C. Taylor and Z. Gleisner and F. Ibrahim and L. Campbell and R. Gilson and N. Brima and R. Jones and C. Atkinson",

note = "Publisher Copyright: {\textcopyright} 2016 British HIV Association.",

year = "2016",

month = may,

day = "1",

doi = "10.1111/hiv.12302",

language = "English",

volume = "17",

pages = "368--372",

journal = "HIV Medicine",

issn = "1464-2662",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "5",

}

Jose, S, Quinn, K, Dunn, D, Cox, A, Sabin, C, Fidler, S, Fisher, M, Gazzard, B, Gilson, R, Gompels, M, Hay, P, Johnson, M, Kegg, S, Leen, C, Martin, F, Nelson, M, Palfreeman, A, Post, F, Pritchard, J, Sachikonye, M, Schwenk, A, Tariq, A, Walsh, J, Hill, T, Jose, S, Phillips, A, Sabin, C, Thornton, A, Dunn, D, Glabay, A, Fisher, M, Perry, N, Tilbury, S, Youssef, E, Churchill, D, Gazzard, B, Nelson, M, Everett, R, Asboe, D, Mandalia, S, Post, F, Korat, H, Taylor, C, Gleisner, Z, Ibrahim, F, Campbell, L, Gilson, R, Brima, N, Jones, R & Atkinson, C 2016, 'Virological failure and development of new resistance mutations according to CD4 count at combination antiretroviral therapy initiation', HIV Medicine, vol. 17, no. 5, pp. 368-372. https://doi.org/10.1111/hiv.12302

TY - JOUR

T1 - Virological failure and development of new resistance mutations according to CD4 count at combination antiretroviral therapy initiation

AU - Jose, Sophie

AU - Quinn, K.

AU - Dunn, David

AU - Cox, A.

AU - Sabin, C.

AU - Fidler, S.

AU - Fisher, M.

AU - Gazzard, B.

AU - Gilson, R.

AU - Gompels, Mark

AU - Hay, Phillip

AU - Johnson, M.

AU - Kegg, Stephen

AU - Leen, Clifford

AU - Martin, Fabiola

AU - Nelson, M.

AU - Palfreeman, Adrian

AU - Post, Frank

AU - Pritchard, Jillian

AU - Sachikonye, Memory

AU - Schwenk, Achim

AU - Tariq, Anjum

AU - Walsh, John

AU - Hill, Teresa

AU - Jose, Sophie

AU - Phillips, Andrew

AU - Sabin, Caroline

AU - Thornton, Alicia

AU - Dunn, David

AU - Glabay, Adam

AU - Fisher, M.

AU - Perry, N.

AU - Tilbury, S.

AU - Youssef, E.

AU - Churchill, D.

AU - Gazzard, B.

AU - Nelson, M.

AU - Everett, R.

AU - Asboe, D.

AU - Mandalia, S.

AU - Post, F.

AU - Korat, H.

AU - Taylor, C.

AU - Gleisner, Z.

AU - Ibrahim, F.

AU - Campbell, L.

AU - Gilson, R.

AU - Brima, N.

AU - Jones, R.

AU - Atkinson, C.

PY - 2016/5/1

Y1 - 2016/5/1

N2 - 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.

AB - 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.

KW - Antiretroviral therapy

KW - CD4 count

KW - HIV resistance

KW - Virological failure

U2 - 10.1111/hiv.12302

DO - 10.1111/hiv.12302

M3 - Article

AN - SCOPUS:84940549930

SN - 1464-2662

VL - 17

SP - 368

EP - 372

JO - HIV Medicine

JF - HIV Medicine

IS - 5

ER -