Inflammation and micronutrient biomarkers predict clinical HIV treatment failure and incident active TB in HIV-infected adults: A case-control study

Rupak Shivakoti, Nikhil Gupte, Srikanth Tripathy, Selvamuthu Poongulali, Cecilia Kanyama, Sima Berendes, Sandra W. Cardoso, Breno R. Santos, Alberto La Rosa, Noluthando Mwelase, Sandy Pillay, Wadzanai Samaneka, Cynthia Riviere, Patcharaphan Sugandhavesa, Robert C Bollinger, Ashwin Balagopal, Richard David Semba, Parul S Christian, Thomas B. Campbell, Amita Gupta

Research output: Contribution to journalArticle

Abstract

Background: Various individual biomarkers of inflammation and micronutrient status, often correlated with each other, are associated with adverse treatment outcomes in human immunodeficiency virus (HIV)-infected adults. The objective of this study was to conduct exploratory factor analysis (EFA) on multiple inflammation and micronutrient biomarkers to identify biomarker groupings (factors) and determine their association with HIV clinical treatment failure (CTF) and incident active tuberculosis (TB). Methods: Within a multicountry randomized trial of antiretroviral therapy (ART) efficacy (PEARLS) among HIV-infected adults, we nested a case-control study (n = 290; 124 cases, 166 controls) to identify underlying factors, based on EFA of 23 baseline (pre-ART) biomarkers of inflammation and micronutrient status. The EFA biomarker groupings results were used in Cox proportional hazards models to study the association with CTF (primary analysis where cases were incident World Health Organization stage 3, 4 or death by 96 weeks of ART) or incident active TB (secondary analysis). Results: In the primary analysis, based on eigenvalues> 1 in the EFA, three factors were extracted: (1) carotenoids), (2) other nutrients, and (3) inflammation. In multivariable-adjusted models, there was an increased hazard of CTF (adjusted hazard ratio (aHR) 1.47, 95% confidence interval (CI)1.17-1.84) per unit increase of inflammation factor score. In the secondary incident active TB case-control analysis, higher scores of the high carotenoids and low interleukin-18 factor was protective against incident active TB (aHR 0.48, 95% CI 0.26-0.87). Conclusion: Factors identified through EFA were associated with adverse outcomes in HIV-infected individuals. Strategies focused on reducing adverse HIV outcomes through therapeutic interventions that target the underlying factor (e.g., inflammation) rather than focusing on an individual observed biomarker might be more effective and warrant further investigation.

Original languageEnglish (US)
Article number161
JournalBMC Medicine
Volume16
Issue number1
DOIs
StatePublished - Sep 24 2018

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Micronutrients
Treatment Failure
Case-Control Studies
Tuberculosis
Biomarkers
Statistical Factor Analysis
HIV
Inflammation
Carotenoids
Confidence Intervals
Interleukin-18
Therapeutics
Proportional Hazards Models
Food

Keywords

  • Antiretroviral therapy
  • Exploratory factor analysis
  • HIV
  • IL-18
  • Inflammation
  • Tuberculosis

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Inflammation and micronutrient biomarkers predict clinical HIV treatment failure and incident active TB in HIV-infected adults : A case-control study. / Shivakoti, Rupak; Gupte, Nikhil; Tripathy, Srikanth; Poongulali, Selvamuthu; Kanyama, Cecilia; Berendes, Sima; Cardoso, Sandra W.; Santos, Breno R.; La Rosa, Alberto; Mwelase, Noluthando; Pillay, Sandy; Samaneka, Wadzanai; Riviere, Cynthia; Sugandhavesa, Patcharaphan; Bollinger, Robert C; Balagopal, Ashwin; Semba, Richard David; Christian, Parul S; Campbell, Thomas B.; Gupta, Amita.

In: BMC Medicine, Vol. 16, No. 1, 161, 24.09.2018.

Research output: Contribution to journalArticle

Shivakoti, R, Gupte, N, Tripathy, S, Poongulali, S, Kanyama, C, Berendes, S, Cardoso, SW, Santos, BR, La Rosa, A, Mwelase, N, Pillay, S, Samaneka, W, Riviere, C, Sugandhavesa, P, Bollinger, RC, Balagopal, A, Semba, RD, Christian, PS, Campbell, TB & Gupta, A 2018, 'Inflammation and micronutrient biomarkers predict clinical HIV treatment failure and incident active TB in HIV-infected adults: A case-control study', BMC Medicine, vol. 16, no. 1, 161. https://doi.org/10.1186/s12916-018-1150-3
Shivakoti, Rupak ; Gupte, Nikhil ; Tripathy, Srikanth ; Poongulali, Selvamuthu ; Kanyama, Cecilia ; Berendes, Sima ; Cardoso, Sandra W. ; Santos, Breno R. ; La Rosa, Alberto ; Mwelase, Noluthando ; Pillay, Sandy ; Samaneka, Wadzanai ; Riviere, Cynthia ; Sugandhavesa, Patcharaphan ; Bollinger, Robert C ; Balagopal, Ashwin ; Semba, Richard David ; Christian, Parul S ; Campbell, Thomas B. ; Gupta, Amita. / Inflammation and micronutrient biomarkers predict clinical HIV treatment failure and incident active TB in HIV-infected adults : A case-control study. In: BMC Medicine. 2018 ; Vol. 16, No. 1.
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abstract = "Background: Various individual biomarkers of inflammation and micronutrient status, often correlated with each other, are associated with adverse treatment outcomes in human immunodeficiency virus (HIV)-infected adults. The objective of this study was to conduct exploratory factor analysis (EFA) on multiple inflammation and micronutrient biomarkers to identify biomarker groupings (factors) and determine their association with HIV clinical treatment failure (CTF) and incident active tuberculosis (TB). Methods: Within a multicountry randomized trial of antiretroviral therapy (ART) efficacy (PEARLS) among HIV-infected adults, we nested a case-control study (n = 290; 124 cases, 166 controls) to identify underlying factors, based on EFA of 23 baseline (pre-ART) biomarkers of inflammation and micronutrient status. The EFA biomarker groupings results were used in Cox proportional hazards models to study the association with CTF (primary analysis where cases were incident World Health Organization stage 3, 4 or death by 96 weeks of ART) or incident active TB (secondary analysis). Results: In the primary analysis, based on eigenvalues> 1 in the EFA, three factors were extracted: (1) carotenoids), (2) other nutrients, and (3) inflammation. In multivariable-adjusted models, there was an increased hazard of CTF (adjusted hazard ratio (aHR) 1.47, 95{\%} confidence interval (CI)1.17-1.84) per unit increase of inflammation factor score. In the secondary incident active TB case-control analysis, higher scores of the high carotenoids and low interleukin-18 factor was protective against incident active TB (aHR 0.48, 95{\%} CI 0.26-0.87). Conclusion: Factors identified through EFA were associated with adverse outcomes in HIV-infected individuals. Strategies focused on reducing adverse HIV outcomes through therapeutic interventions that target the underlying factor (e.g., inflammation) rather than focusing on an individual observed biomarker might be more effective and warrant further investigation.",
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author = "Rupak Shivakoti and Nikhil Gupte and Srikanth Tripathy and Selvamuthu Poongulali and Cecilia Kanyama and Sima Berendes and Cardoso, {Sandra W.} and Santos, {Breno R.} and {La Rosa}, Alberto and Noluthando Mwelase and Sandy Pillay and Wadzanai Samaneka and Cynthia Riviere and Patcharaphan Sugandhavesa and Bollinger, {Robert C} and Ashwin Balagopal and Semba, {Richard David} and Christian, {Parul S} and Campbell, {Thomas B.} and Amita Gupta",
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T1 - Inflammation and micronutrient biomarkers predict clinical HIV treatment failure and incident active TB in HIV-infected adults

T2 - A case-control study

AU - Shivakoti, Rupak

AU - Gupte, Nikhil

AU - Tripathy, Srikanth

AU - Poongulali, Selvamuthu

AU - Kanyama, Cecilia

AU - Berendes, Sima

AU - Cardoso, Sandra W.

AU - Santos, Breno R.

AU - La Rosa, Alberto

AU - Mwelase, Noluthando

AU - Pillay, Sandy

AU - Samaneka, Wadzanai

AU - Riviere, Cynthia

AU - Sugandhavesa, Patcharaphan

AU - Bollinger, Robert C

AU - Balagopal, Ashwin

AU - Semba, Richard David

AU - Christian, Parul S

AU - Campbell, Thomas B.

AU - Gupta, Amita

PY - 2018/9/24

Y1 - 2018/9/24

N2 - Background: Various individual biomarkers of inflammation and micronutrient status, often correlated with each other, are associated with adverse treatment outcomes in human immunodeficiency virus (HIV)-infected adults. The objective of this study was to conduct exploratory factor analysis (EFA) on multiple inflammation and micronutrient biomarkers to identify biomarker groupings (factors) and determine their association with HIV clinical treatment failure (CTF) and incident active tuberculosis (TB). Methods: Within a multicountry randomized trial of antiretroviral therapy (ART) efficacy (PEARLS) among HIV-infected adults, we nested a case-control study (n = 290; 124 cases, 166 controls) to identify underlying factors, based on EFA of 23 baseline (pre-ART) biomarkers of inflammation and micronutrient status. The EFA biomarker groupings results were used in Cox proportional hazards models to study the association with CTF (primary analysis where cases were incident World Health Organization stage 3, 4 or death by 96 weeks of ART) or incident active TB (secondary analysis). Results: In the primary analysis, based on eigenvalues> 1 in the EFA, three factors were extracted: (1) carotenoids), (2) other nutrients, and (3) inflammation. In multivariable-adjusted models, there was an increased hazard of CTF (adjusted hazard ratio (aHR) 1.47, 95% confidence interval (CI)1.17-1.84) per unit increase of inflammation factor score. In the secondary incident active TB case-control analysis, higher scores of the high carotenoids and low interleukin-18 factor was protective against incident active TB (aHR 0.48, 95% CI 0.26-0.87). Conclusion: Factors identified through EFA were associated with adverse outcomes in HIV-infected individuals. Strategies focused on reducing adverse HIV outcomes through therapeutic interventions that target the underlying factor (e.g., inflammation) rather than focusing on an individual observed biomarker might be more effective and warrant further investigation.

AB - Background: Various individual biomarkers of inflammation and micronutrient status, often correlated with each other, are associated with adverse treatment outcomes in human immunodeficiency virus (HIV)-infected adults. The objective of this study was to conduct exploratory factor analysis (EFA) on multiple inflammation and micronutrient biomarkers to identify biomarker groupings (factors) and determine their association with HIV clinical treatment failure (CTF) and incident active tuberculosis (TB). Methods: Within a multicountry randomized trial of antiretroviral therapy (ART) efficacy (PEARLS) among HIV-infected adults, we nested a case-control study (n = 290; 124 cases, 166 controls) to identify underlying factors, based on EFA of 23 baseline (pre-ART) biomarkers of inflammation and micronutrient status. The EFA biomarker groupings results were used in Cox proportional hazards models to study the association with CTF (primary analysis where cases were incident World Health Organization stage 3, 4 or death by 96 weeks of ART) or incident active TB (secondary analysis). Results: In the primary analysis, based on eigenvalues> 1 in the EFA, three factors were extracted: (1) carotenoids), (2) other nutrients, and (3) inflammation. In multivariable-adjusted models, there was an increased hazard of CTF (adjusted hazard ratio (aHR) 1.47, 95% confidence interval (CI)1.17-1.84) per unit increase of inflammation factor score. In the secondary incident active TB case-control analysis, higher scores of the high carotenoids and low interleukin-18 factor was protective against incident active TB (aHR 0.48, 95% CI 0.26-0.87). Conclusion: Factors identified through EFA were associated with adverse outcomes in HIV-infected individuals. Strategies focused on reducing adverse HIV outcomes through therapeutic interventions that target the underlying factor (e.g., inflammation) rather than focusing on an individual observed biomarker might be more effective and warrant further investigation.

KW - Antiretroviral therapy

KW - Exploratory factor analysis

KW - HIV

KW - IL-18

KW - Inflammation

KW - Tuberculosis

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