Plasma calprotectin as a biomarker of mortality at antiretroviral treatment initiation in advanced HIV – pilot study [version 2; peer review: 2 approved]
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 collecte...
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| Format: | Article |
| Language: | English |
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Wellcome
2020-11-01
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| Series: | Wellcome Open Research |
| Online Access: | https://wellcomeopenresearch.org/articles/5-46/v2 |
| _version_ | 1818610233342164992 |
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| author | Faith W. Kamau Agnes Gwela Andrew K. Nyerere Victor Riitho James M. Njunge Moses M. Ngari Andrew J. Prendergast James A. Berkley |
| author_facet | Faith W. Kamau Agnes Gwela Andrew K. Nyerere Victor Riitho James M. Njunge Moses M. Ngari Andrew J. Prendergast James A. Berkley |
| author_sort | Faith W. Kamau |
| collection | DOAJ |
| description | 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) µg/ml in cases (n=39) and 5.01 (1.92–11.5) µg/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. |
| first_indexed | 2024-12-16T15:11:11Z |
| format | Article |
| id | doaj.art-fcd9a12ad3e3415eb8ec07594b01b987 |
| institution | Directory Open Access Journal |
| issn | 2398-502X |
| language | English |
| last_indexed | 2024-12-16T15:11:11Z |
| publishDate | 2020-11-01 |
| publisher | Wellcome |
| record_format | Article |
| series | Wellcome Open Research |
| spelling | doaj.art-fcd9a12ad3e3415eb8ec07594b01b9872022-12-21T22:26:58ZengWellcomeWellcome Open Research2398-502X2020-11-01510.12688/wellcomeopenres.15563.217976Plasma calprotectin as a biomarker of mortality at antiretroviral treatment initiation in advanced HIV – pilot study [version 2; peer review: 2 approved]Faith W. Kamau0Agnes Gwela1Andrew K. Nyerere2Victor Riitho3James M. Njunge4Moses M. Ngari5Andrew J. Prendergast6James A. Berkley7Department of Molecular Biology and Biotechnology, Pan African University Institute for Basic Sciences, Technology and Innovation, Juja, Nairobi, 62000-00200, KenyaClinical Research, KEMRI/Wellcome Trust Research Programme, Kilifi, Kilifi County, 320-80108, KenyaDepartment of Medical Microbiology, Jomo Kenyatta University of Agriculture and Technology, Juja, Nairobi, 62000–00200, KenyaBlizard Institute, Queen Mary University of London, London, London, E1 2AT, UKClinical Research, KEMRI/Wellcome Trust Research Programme, Kilifi, Kilifi County, 320-80108, KenyaClinical Research, KEMRI/Wellcome Trust Research Programme, Kilifi, Kilifi County, 320-80108, KenyaBlizard Institute, Queen Mary University of London, London, London, E1 2AT, UKClinical Research, KEMRI/Wellcome Trust Research Programme, Kilifi, Kilifi County, 320-80108, KenyaBackground: 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) µg/ml in cases (n=39) and 5.01 (1.92–11.5) µg/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.https://wellcomeopenresearch.org/articles/5-46/v2 |
| spellingShingle | Faith W. Kamau Agnes Gwela Andrew K. Nyerere Victor Riitho James M. Njunge Moses M. Ngari Andrew J. Prendergast James A. Berkley Plasma calprotectin as a biomarker of mortality at antiretroviral treatment initiation in advanced HIV – pilot study [version 2; peer review: 2 approved] Wellcome Open Research |
| title | Plasma calprotectin as a biomarker of mortality at antiretroviral treatment initiation in advanced HIV – pilot study [version 2; peer review: 2 approved] |
| title_full | Plasma calprotectin as a biomarker of mortality at antiretroviral treatment initiation in advanced HIV – pilot study [version 2; peer review: 2 approved] |
| title_fullStr | Plasma calprotectin as a biomarker of mortality at antiretroviral treatment initiation in advanced HIV – pilot study [version 2; peer review: 2 approved] |
| title_full_unstemmed | Plasma calprotectin as a biomarker of mortality at antiretroviral treatment initiation in advanced HIV – pilot study [version 2; peer review: 2 approved] |
| title_short | Plasma calprotectin as a biomarker of mortality at antiretroviral treatment initiation in advanced HIV – pilot study [version 2; peer review: 2 approved] |
| title_sort | plasma calprotectin as a biomarker of mortality at antiretroviral treatment initiation in advanced hiv pilot study version 2 peer review 2 approved |
| url | https://wellcomeopenresearch.org/articles/5-46/v2 |
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