Plasma calprotectin as a biomarker of mortality at antiretroviral treatment initiation in advanced HIV – pilot study


Wellcome Open Res

Background: In advanced HIV, significant mortality occurs soon after starting antiretroviral treatment (ART) in low- and middle-incomes countries. Calprotectin is a biomarker of innate response to infection and inflammatory conditions. We examined the association between plasma calprotectin collected before ART treatment and mortality among individuals with advanced HIV. Methods: We conducted a pilot case-cohort study among HIV infected adults and adolescents over 13 years old with CD4+ <100/mm3 at ART initiation at two Kenyan sites. Participants received three factorial randomised interventions in addition to ART within the REALITY trial (ISRCTN43622374). Calprotectin collected at baseline (before ART) and after 4 weeks of treatment was measured in archived plasma of those who died within 24 weeks (cases) and randomly selected participants who survived (non-cases). Association with mortality was assessed using Cox proportional hazards models with inverse sampling probability weights and adjusted for age, sex, site, BMI, viral load, randomised treatments, and clustered by CD4+ count (0-24, 25-49, and 50-99 cells/mm3). Results: Baseline median (IQR) plasma calprotectin was 6.82 (2.65-12.5) microg/ml in cases (n=39) and 5.01 (1.92-11.5) microg/ml in non-cases (n=58). Baseline calprotectin was associated with age, neutrophil count and the presence of cough, but not other measured indicators of infection. In adjusted multivariable models, baseline calprotectin was associated with subsequent mortality: HR 1.64 (95% CI 1.11 - 2.42) and HR 2.77 (95% CI 1.58 - 4.88) for deaths during the first twenty-four and four weeks respectively. Calprotectin levels fell between baseline and 4 weeks among both cases and non-cases irrespective of randomised interventions. Conclusions: Among individuals with advanced HIV starting ART in Kenya, plasma calprotectin may have potential as a biomarker of early mortality. Validation in larger studies, comparison with other biomarkers and investigation of the sources of infection and inflammation are warranted. Kamau, F. W., Gwela, A., Nyerere, A. K., Riitho, V., Njunge, J. M., Ngari, M. M., Prendergast, A. J., Berkley, J. A.

Pages:46, Volume:5, Edition:12/22/2020, Date,


Notes:Kamau, Faith W|Gwela, Agnes|Nyerere, Andrew K|Riitho, Victor|Njunge, James M|Ngari, Moses M|Prendergast, Andrew J|Berkley, James A|eng|MR/P022251/1/MRC_/Medical Research Council/United Kingdom|MC_UU_12023/23/MRC_/Medical Research Council/United Kingdom|MC_UU_12023/26/MRC_/Medical Research Council/United Kingdom|EP-C-15-003/EPA/|Wellcome Trust/United Kingdom|England|2020/12/22 06:00|Wellcome Open Res. 2020 Nov 27;5:46. doi: 10.12688/wellcomeopenres.15563.2. eCollection 2020.

ISBN: 2398-502X (Print)|2398-502X (Linking) Permanent ID: PMC7722532 Accession Number: 33336080

Author Address: Clinical Research, KEMRI/Wellcome Trust Research Programme, Kilifi, Kilifi County, 320-80108, Kenya.|Department of Molecular Biology and Biotechnology, Pan African University Institute for Basic Sciences, Technology and Innovation, Juja, Nairobi, 62000-00200, Kenya.|Childhood Acute Illness & Nutrition (CHAIN) Network, Nairobi, Nairobi, 43640-00100, Kenya.|Department of Medical Microbiology, Jomo Kenyatta University of Agriculture and Technology, Juja, Nairobi, 62000-00200, Kenya.|Blizard Institute, Queen Mary University of London, London, London, E1 2AT, UK.|Centre for Tropical Medicine & Global Health, University of Oxford, Oxford, Oxfordshire, OX3 7FZ, UK.