TY - JOUR
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 D.
AU - Christian, Parul
AU - Campbell, Thomas B.
AU - Gupta, Amita
N1 - Publisher Copyright:
© 2018 The Author(s).
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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U2 - 10.1186/s12916-018-1150-3
DO - 10.1186/s12916-018-1150-3
M3 - Article
C2 - 30244671
AN - SCOPUS:85053848322
SN - 1741-7015
VL - 16
JO - BMC medicine
JF - BMC medicine
IS - 1
M1 - 161
ER -