Bell Gorrod, H. orcid.org/0000-0001-8054-8073, Fox, M.P., Boulle, A. et al. (5 more authors) (2020) The impact of delayed switch to second-line antiretroviral therapy on mortality, depending on failure time definition and CD4 count at failure. American Journal of Epidemiology, 189 (8). pp. 811-819. ISSN 0002-9262
Abstract
Little is known about the functional relationship of delaying second-line treatment initiation for HIV-positive patients and mortality, given a patient’s immune status. We included 7255 patients starting antiretroviral therapy between 2004-2017, from 9 South African cohorts, with virological failure and complete baseline data. We estimated the impact of switch time on the hazard of death using inverse probability of treatment weighting (IPTW) of marginal structural models. The non-linear relationship between month of switch and the 5-year survival probability, stratified by CD4 count at failure, was estimated with targeted maximum likelihood estimation (TMLE). We adjusted for measured time-varying confounding by CD4 count, viral load and visit frequency. 5-year mortality was estimated as 10.5% (2.2%; 18.8%) for immediate switch and as 26.6% (20.9%; 32.3%) for no switch (49.9% if CD4 count<100 cells/mm3). The hazard of death was estimated to be 0.40 (95%CI: 0.33-0.48) times lower if everyone had been switched immediately compared to never. The shorter the delay in switching, the lower the hazard of death, e.g. delaying 30-60 days reduced the hazard 0.52 (0.41-0.65) times, and 60-120 days 0.56 (0.47-0.66) times. Early treatment switch is particularly important for patients with low CD4 counts at failure.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. This is an author-produced version of a paper subsequently published in American Journal of Epidemiology. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | HIV; treatment switching; second-line ART; causal inference; targeted learning |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Health and Related Research (Sheffield) > ScHARR - Sheffield Centre for Health and Related Research |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 18 Feb 2020 11:56 |
Last Modified: | 08 Dec 2021 11:57 |
Status: | Published |
Publisher: | Oxford University Press (OUP) |
Refereed: | Yes |
Identification Number: | 10.1093/aje/kwaa049 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:157133 |