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Discordant Immune Response with Antiretroviral Therapy in HIV-1: A Systematic Review of Clinical Outcomes

Kelly, C; Gaskell, KM; Richardson, M; Klein, N; Garner, P; MacPherson, P; (2016) Discordant Immune Response with Antiretroviral Therapy in HIV-1: A Systematic Review of Clinical Outcomes. PLoS ONE , 11 (6) , Article e0156099. 10.1371/journal.pone.0156099. Green open access

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Abstract

BACKGROUND: A discordant immune response (DIR) is a failure to satisfactorily increase CD4 counts on ART despite successful virological control. Literature on the clinical effects of DIR has not been systematically evaluated. We aimed to summarise the risk of mortality, AIDS and serious non-AIDS events associated with DIR with a systematic review. METHODS: The protocol is registered with the Centre for Review Dissemination, University of York (registration number CRD42014010821). Included studies investigated the effect of DIR on mortality, AIDS, or serious non-AIDS events in cohort studies or cohorts contained in arms of randomised controlled trials for adults aged 16 years or older. DIR was classified as a suboptimal CD4 count (as defined by the study) despite virological suppression following at least 6 months of ART. We systematically searched PubMed, Embase, and the Cochrane Library to December 2015. Risk of bias was assessed using the Cochrane tool for assessing risk of bias in cohort studies. Two authors applied inclusion criteria and one author extracted data. Risk ratios were calculated for each clinical outcome reported. RESULTS: Of 20 studies that met the inclusion criteria, 14 different definitions of DIR were used. Risk ratios for mortality in patients with and without DIR ranged between 1.00 (95% CI 0.26 to 3.92) and 4.29 (95% CI 1.96 to 9.38) with the majority of studies reporting a 2 to 3 fold increase in risk. CONCLUSIONS: DIR is associated with a marked increase in mortality in most studies but definitions vary widely. We propose a standardised definition to aid the development of management options for DIR.

Type: Article
Title: Discordant Immune Response with Antiretroviral Therapy in HIV-1: A Systematic Review of Clinical Outcomes
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0156099
Publisher version: https://doi.org/10.1371/journal.pone.0156099
Language: English
Additional information: Copyright © 2016 Kelly et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1504765
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