Role of HIV Infection Duration and CD4 Cell Level at Initiation of Combination Anti-Retroviral Therapy on Risk of Failure

Title: Role of HIV Infection Duration and CD4 Cell Level at Initiation of Combination Anti-Retroviral Therapy on Risk of Failure
Authors: Lodi, S
Phillips, A
Fidler, S
Hawkins, D
Gilson, R
McLean, K
Fisher, M
Post, F
Johnson, AM
Walker-Nthenda, L
Dunn, D
Porter, K
Item Type: Journal Article
Abstract: Background: 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. Methods: 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). Results: Of 1075 starting cART at a median (IQR) CD4 count 272 (190,370) cells/mm3 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. Conclusion: 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.
Issue Date: 24-Sep-2013
Date of Acceptance: 16-Aug-2013
ISSN: 1932-6203
Publisher: Public Library of Science
Journal / Book Title: PLoS ONE
Volume: 8
Issue: 9
Copyright Statement: © 2013 Lodi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
Anti-HIV Agents
Anti-Retroviral Agents
CD4 Lymphocyte Count
CD4-Positive T-Lymphocytes
Drug Resistance, Viral
Drug Therapy, Combination
HIV Infections
HIV Seropositivity
Treatment Failure
UK Register of HIV
MD Multidisciplinary
General Science & Technology
Publication Status: Published
Article Number: ARTN e75608
Appears in Collections:Department of Medicine
Faculty of Medicine

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