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Prevalence and clinical outcomes of poor immune response despite virologically suppressive antiretroviral therapy among children and adolescents with HIV in Europe and Thailand: cohort study

EPPICC, CC; Chappell, E; Goodall, R; Judd, A; Gibb, D; Collins, I; (2020) Prevalence and clinical outcomes of poor immune response despite virologically suppressive antiretroviral therapy among children and adolescents with HIV in Europe and Thailand: cohort study. Clinical Infectious Diseases , 70 (3) pp. 404-415. 10.1093/cid/ciz253. Green open access

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Abstract

Background: In HIV-positive adults, low CD4 cell counts despite fully suppressed HIV-1 RNA on antiretroviral therapy (ART) have been associated with increased risk of morbidity and mortality. We assessed the prevalence and outcomes of poor immune response (PIR) in children on suppressive ART. Methods: Sixteen cohorts from the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) contributed data. Children aged<18 years at ART initiation, with sustained viral suppression (VS) (≤400copies/mL) for ≥1 year were included. The prevalence of PIR (defined as WHO advanced/severe immunosuppression for age: CD4%<30% in children aged<12 months, CD4%<25% in 12-35 months, CD4%<20% in 36-59 months; CD4%<15%/CD4<350 cells/mm3 in ≥5-years) at 1 year of VS was described. Factors associated with PIR were assessed using logistic regression. Rates of AIDS or death on suppressive ART were calculated by PIR status. Results: Of 2318 children included, median age was 6.4 [IQR, 2.1, 10.4] years and 68% had advanced/severe immunosuppression at ART initiation. At 1 year of VS, 12% had PIR. In multivariable analysis, PIR was associated with older age and worse immunological stage at ART start, hepatitis-B coinfection and residing in Thailand (all p≤0.03). Rates of AIDS/death (95% CI) per 100,000 person-years were 1052 (547, 2022) among PIR versus 261 (166, 409) among immune responders; rate ratio of 4.04 (1.83, 8.92), p<0.001. Conclusions: One in eight children in our cohort experienced PIR despite sustained viral suppression. While the overall rate of AIDS/death was low, children with PIR had four-fold increase in risk of event as compared to immune responders.

Type: Article
Title: Prevalence and clinical outcomes of poor immune response despite virologically suppressive antiretroviral therapy among children and adolescents with HIV in Europe and Thailand: cohort study
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/cid/ciz253
Publisher version: http://doi.org/10.1093/cid/ciz253
Language: English
Additional information: Copyright © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. 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 reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: HIV, children, antiretroviral therapy, poor immune response, viral suppression
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 > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
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 > Population, Policy and Practice Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10071384
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