Discordant Immune Response with Antiretroviral Therapy in HIV-1: A Systematic Review of Clinical Outcomes.
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.
Institute of Translation Medicine, University of Liverpool, Liverpool, United Kingdom.|Malawi Liverpool Wellcome Trust Clinical Research Program, Blantyre, Malawi.
Christine
C
Kelly
Malawi Liverpool Wellcome Trust Clinical Research Program, Blantyre, Malawi.|London School of Hygiene and Tropical Medicine, London, United Kingdom.
Katherine M
KM
Gaskell
Centre for Evidence Synthesis, Department of Clinical Sciences, Liverpool School of Tropicla Medicine, Liverpool, United Kingdom.
Marty
M
Richardson
Institute of Child Health, University College London, London, United Kingdom.
Nigel
N
Klein
Centre for Evidence Synthesis, Department of Clinical Sciences, Liverpool School of Tropicla Medicine, Liverpool, United Kingdom.
Paul
P
Garner
Department of Public Health and Policy, University of Liverpool, Liverpool, United Kingdom.|Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.|North West Public Health England Centre, Liverpool, United Kingdom.
Peter
P
MacPherson
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D044966:Anti-Retroviral Agents