Virological failure and development of new resistance mutations according to CD4 count at combination antiretroviral therapy initiation
File(s)Jose_et_al-2016-HIV_Medicine.pdf (66.56 KB)
Published version
Author(s)
Type
Journal Article
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.
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.
Date Issued
2015-08-25
Date Acceptance
2015-07-01
Citation
HIV Medicine, 2015, 17 (5), pp.368-372
ISSN
1464-2662
Publisher
Wiley
Start Page
368
End Page
372
Journal / Book Title
HIV Medicine
Volume
17
Issue
5
Copyright Statement
© 2015 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Sponsor
Medical Research Council (MRC)
Grant Number
MR/L00528X/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Infectious Diseases
antiretroviral therapy
CD4 count
HIV resistance
virological failure
HIV-INFECTION
HAART
UK CHIC and UK HDRD Steering Committees
Virology
1103 Clinical Sciences
Publication Status
Published