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

TitleInflammation and micronutrient biomarkers predict clinical HIV treatment failure and incident active TB in HIV-infected adults: a case-control study.
Publication TypeJournal Article
Year of Publication2018
AuthorsShivakoti 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 P, Campbell TB, Gupta A
Corporate AuthorsNWCS 319 and PEARLS study team
JournalBMC Med
Volume16
Issue1
Pagination161
Date Published2018 09 24
ISSN1741-7015
KeywordsAdult, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Biomarkers, Case-Control Studies, Female, HIV Infections, Humans, Inflammation, Male, Micronutrients, Middle Aged, Proportional Hazards Models, Trace Elements, Treatment Failure, Tuberculosis, Young Adult
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.

DOI10.1186/s12916-018-1150-3
Alternate JournalBMC Med
PubMed ID30244671
PubMed Central IDPMC6151930
Grant ListUM1 AI106701 / / National Institute of Allergy and Infectious Diseases / International
UM1 AI068634 / / National Institute of Allergy and Infectious Diseases / International
R01 AI080417 / / National Institute of Allergy and Infectious Diseases / International
UM1 AI068634 / AI / NIAID NIH HHS / United States
K99 HD089753 / HD / NICHD NIH HHS / United States
R01 AI080417 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069463 / AI / NIAID NIH HHS / United States
K99 HD089753 / / Eunice Kennedy Shriver National Institute of Child Health and Human Development / International
UM1 AI068636 / / National Institute of Allergy and Infectious Diseases / International
UM1 AI106701 / AI / NIAID NIH HHS / United States
UM1 AI069465 / AI / NIAID NIH HHS / United States
UM1 AI069465 / / National Institute of Allergy and Infectious Diseases / International
UM1 AI068636 / AI / NIAID NIH HHS / United States