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

Abstract

BackgroundVarious 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).MethodsWithin 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).ResultsIn 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).ConclusionFactors 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.Electronic supplementary materialThe online version of this article (10.1186/s12916-018-1150-3) contains supplementary material, which is available to authorized users.

A Parsimonious Host Inflammatory Biomarker Signature Predicts Incident Tuberculosis and Mortality in Advanced Human Immunodeficiency Virus

“…They found several blood TB biomarkers that overlap with our study including CXCL10, IFNγ [21]. Two other studies in PLHIV also identified CXCL10 as predictive of incident TB [32,33]. Baseline IL-6 predicted both TB and death in our analysis and corroborates findings in other studies [34][35][36][37][38][39].…”

“…Our data contribute and expand that of our previous studies showing the importance of IFNγ and CXCL10 (IP-10) in robustly classifying active TB in patients with advanced HIV starting ART [22,32]. In a cohort of HIV-positive, less immunosuppressed patients that were starting isoniazid prophylactic therapy, Lesosky et al compared plasma biomarkers from those with incident TB to those with either prevalent TB or no TB.…”

Malnutrition leads to increased inflammation and expression of tuberculosis risk signatures in recently exposed household contacts of pulmonary tuberculosis

“…Analysis of baseline samples of a longitudinal cohort study nested within a randomized clinical trial among HIV+ adults in Haiti found that vitamin A deficiency was a good predicter of incident tuberculosis ( 51 ). Higher levels of pro-vitamin A carotenoids (that are metabolized intracellularly to vitamin A) in conjunction with low IL-18 were associated with reduced hazard of incident TB among 290 HIV-infected individuals (aHR 0.48; 95% CI 0.26–0.87) ( 52 ). Vitamin D deficiency (<20 ng/mL) is associated with incident TB in contacts of TB patients and HIV-infected individuals (HR 2.89 [95%CI 1.31-7.41] and aHR 3.66 [95% CI 1.16-11.51] respectively) ( 50 , 53 ) and separately vitamin D (25(OH)D) <75nmol/l associated with an OR of 6.5 (95%CI 1.8-23.5) for increased risk of TB among contacts of TB cases in Greenland ( 54 ).…”

Global and regional trends of people living with HIV aged 50 and over: Estimates and projections for 2000–2020

“…The underlying pathophysiological cause is chronic inflammation by chronic immune activation. PLHIV have higher markers of inflammation [35] and HIV treatment failure increases with increased inflammation [36]. The process of chronic inflammation is further accentuated by other chronic diseases, as well as socio-economic and behavioural factors [37].…”