Role of HIV infection duration and CD4 cell level at initiation of combination anti-retroviral therapy on risk of failure.

<h4>Background</h4>The development of HIV drug resistance and subsequent virological failure are often cited as potential disadvantages of early cART initiation. However, their long-term probability is not known, and neither is the role of duration of infection at the time of initiation....

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Main Authors: Sara Lodi, Andrew Phillips, Sarah Fidler, David Hawkins, Richard Gilson, Ken McLean, Martin Fisher, Frank Post, Anne M Johnson, Louise Walker-Nthenda, David Dunn, Kholoud Porter, UK Register of HIV
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24086588/?tool=EBI
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spelling doaj-35262eac5cb748d88f39bf78f2fe381c2021-03-03T22:51:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0189e7560810.1371/journal.pone.0075608Role of HIV infection duration and CD4 cell level at initiation of combination anti-retroviral therapy on risk of failure.Sara LodiAndrew PhillipsSarah FidlerDavid HawkinsRichard GilsonKen McLeanMartin FisherFrank PostAnne M JohnsonLouise Walker-NthendaDavid DunnKholoud PorterUK Register of HIV<h4>Background</h4>The development of HIV drug resistance and subsequent virological failure are often cited as potential disadvantages of early cART initiation. However, their long-term probability is not known, and neither is the role of duration of infection at the time of initiation.<h4>Methods</h4>Patients enrolled in the UK Register of HIV seroconverters were followed-up from cART initiation to last HIV-RNA measurement. Through survival analysis we examined predictors of virologic failure (2HIV-RNA ≥400 c/l while on cART) including CD4 count and HIV duration at initiation. We also estimated the cumulative probabilities of failure and drug resistance (from the available HIV nucleotide sequences) for early initiators (cART within 12 months of seroconversion).<h4>Results</h4>Of 1075 starting cART at a median (IQR) CD4 count 272 (190,370) cells/mm(3) and HIV duration 3 (1,6) years, virological failure occurred in 163 (15%). Higher CD4 count at initiation, but not HIV infection duration at cART initiation, was independently associated with lower risk of failure (p=0.033 and 0.592 respectively). Among 230 patients initiating cART early, 97 (42%) discontinued it after a median of 7 months; cumulative probabilities of resistance and failure by 8 years were 7% (95% CI 4,11) and 19% (13,25), respectively.<h4>Conclusion</h4>Although the rate of discontinuation of early cART in our cohort was high, the long-term rate of virological failure was low. Our data do not support early cART initiation being associated with increased risk of failure and drug resistance.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24086588/?tool=EBI
collection DOAJ
language English
format Article
sources DOAJ
author Sara Lodi
Andrew Phillips
Sarah Fidler
David Hawkins
Richard Gilson
Ken McLean
Martin Fisher
Frank Post
Anne M Johnson
Louise Walker-Nthenda
David Dunn
Kholoud Porter
UK Register of HIV
spellingShingle Sara Lodi
Andrew Phillips
Sarah Fidler
David Hawkins
Richard Gilson
Ken McLean
Martin Fisher
Frank Post
Anne M Johnson
Louise Walker-Nthenda
David Dunn
Kholoud Porter
UK Register of HIV
Role of HIV infection duration and CD4 cell level at initiation of combination anti-retroviral therapy on risk of failure.
PLoS ONE
author_facet Sara Lodi
Andrew Phillips
Sarah Fidler
David Hawkins
Richard Gilson
Ken McLean
Martin Fisher
Frank Post
Anne M Johnson
Louise Walker-Nthenda
David Dunn
Kholoud Porter
UK Register of HIV
author_sort Sara Lodi
title Role of HIV infection duration and CD4 cell level at initiation of combination anti-retroviral therapy on risk of failure.
title_short Role of HIV infection duration and CD4 cell level at initiation of combination anti-retroviral therapy on risk of failure.
title_full Role of HIV infection duration and CD4 cell level at initiation of combination anti-retroviral therapy on risk of failure.
title_fullStr Role of HIV infection duration and CD4 cell level at initiation of combination anti-retroviral therapy on risk of failure.
title_full_unstemmed Role of HIV infection duration and CD4 cell level at initiation of combination anti-retroviral therapy on risk of failure.
title_sort role of hiv infection duration and cd4 cell level at initiation of combination anti-retroviral therapy on risk of failure.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2013-01-01
description <h4>Background</h4>The development of HIV drug resistance and subsequent virological failure are often cited as potential disadvantages of early cART initiation. However, their long-term probability is not known, and neither is the role of duration of infection at the time of initiation.<h4>Methods</h4>Patients enrolled in the UK Register of HIV seroconverters were followed-up from cART initiation to last HIV-RNA measurement. Through survival analysis we examined predictors of virologic failure (2HIV-RNA ≥400 c/l while on cART) including CD4 count and HIV duration at initiation. We also estimated the cumulative probabilities of failure and drug resistance (from the available HIV nucleotide sequences) for early initiators (cART within 12 months of seroconversion).<h4>Results</h4>Of 1075 starting cART at a median (IQR) CD4 count 272 (190,370) cells/mm(3) and HIV duration 3 (1,6) years, virological failure occurred in 163 (15%). Higher CD4 count at initiation, but not HIV infection duration at cART initiation, was independently associated with lower risk of failure (p=0.033 and 0.592 respectively). Among 230 patients initiating cART early, 97 (42%) discontinued it after a median of 7 months; cumulative probabilities of resistance and failure by 8 years were 7% (95% CI 4,11) and 19% (13,25), respectively.<h4>Conclusion</h4>Although the rate of discontinuation of early cART in our cohort was high, the long-term rate of virological failure was low. Our data do not support early cART initiation being associated with increased risk of failure and drug resistance.
url https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24086588/?tool=EBI
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