A parsimonious host inflammatory biomarker signature predicts incident TB and mortality in advanced HIV

Citation: Yukari C Manabe, MD; Bruno B Andrade; Nikhil Gupte; Samantha Leong; Manisha Kintali; Mitch Matoga; Cynthia Riviere; Wadzanai Sameneka; Javier R Lama; Kogieleum Naidoo; Yue Zhao; William Evan Johnson; Jerrold Ellner, MD; Mina C Hosseinipour; Gregory P Bisson; Padmini Salgame, PhD; Amita Gupta, MD. A parsimonious host inflammatory biomarker signature predicts incident TB and mortality in advanced HIV. Clin Infect Dis. 2019 Nov 25. pii: ciz1147. doi: 10.1093/cid/ciz1147. [Epub ahead of print]. PMID: 31761933.

Access full article:

https://www.ncbi.nlm.nih.gov/pubmed/31761933

BACKGROUND:
People with advanced HIV (CD4<50) remain at high risk of TB or death despite the initiation of antiretroviral therapy. We aimed to identify immunological profiles that were most predictive of incident TB disease and death.

METHODS:
The REMEMBER randomized clinical trial enrolled 850 participants with HIV (CD4<50 cells/µL) at ART initiation to receive either empiric TB treatment or isoniazid preventive therapy (IPT). A case-cohort study (n=257) stratified by country and treatment arm was performed. Cases were defined as incident TB or all-cause death within 48 weeks after ART initiation. Using multiplexed immunoassay panels and ELISA, 26 biomarkers were assessed in plasma.

RESULTS:
52 (6.1%) of 850 participants developed TB; 47 (5.5%) died (13 of whom had antecedent TB). Biomarkers associated with incident TB overlapped with those associated with death (IL-1β, IL-6). Biomarker levels declined over time in individuals with incident TB while remaining persistently elevated in those who died. Dividing the cohort into development and validation sets, the final model of 6 biomarkers (CXCL10, IL-1β, IL-10, sCD14, TNF-α, and TNF-β) achieved a sensitivity of 0.90 (95% CI: 0.87-0.94) and a specificity of 0.71(95% CI: 0.68-0.75) with an area under the curve (AUC) of 0.81 (95% CI: 0.78-0.83) for incident TB.

CONCLUSION:
Among people with advanced HIV, a parsimonious inflammatory biomarker signature predicted those at highest risk for developing TB despite initiation of ART and TB preventive therapies. The signature may be a promising stratification tool to select patients who may benefit from increased monitoring and novel interventions.

Categories

CRS
Topics

Clinical Trials

NWCS 445: Novel Biomarkers to Shorten TB Treatment

Objectives: Primary: To develop a highly predictive algorithm that identifies TB patients who will be cured by treatment...

Read More

A5302:  BioBank for Surrogate Marker Research for TB...

Primary Objective To obtain sputum, serum, urine, and peripheral blood mononuclear cells (PBMCs) for central TB biorepository...

Read More

A5300B/I2003B/PHOENIX, Protecting Households On Exposure to...

This study will compare the efficacy and safety of 26 weeks of delamanid (DLM) versus 26 weeks of isoniazid (INH) for preventing...

Read More

P1060:  Phase II, parallel, randomized, clinical trials...

A single dose of nevirapine (SD NVP) given to an HIV infected pregnant woman followed by a single dose to her infant has been...

Read More

A5128: Consent for Use of Stored Patient Specimens for...

The purpose of this study is to obtain informed consent to use stored human biological materials (HBM) (e.g., blood and other...

Read More