ArticlePloS one2015
C-reactive protein (CRP), interferon gamma-inducible protein 10 (IP-10), and lipopolysaccharide (LPS) are associated with risk of tuberculosis after initiation of antiretroviral therapy in resource-limited settings.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Anemia, Iron Status, and HIV: A Systematic Review of the Evidence.Advances in nutrition (Bethesda, Md.) · 2020Pooled it
- Relationship Between Anemia and Systemic Inflammation in People Living With HIV and Tuberculosis: A Sub-Analysis of the CADIRIS Clinical Trial.Frontiers in immunology · 2022Trial
- Integrative Multi-Omics Reveals Serum Markers of Tuberculosis in Advanced HIV.Frontiers in immunology · 2021Trial
- Inflammation and micronutrient biomarkers predict clinical HIV treatment failure and incident active TB in HIV-infected adults: a case-control study.BMC medicine · 2018Trial
- Vitamin A and D Deficiencies Associated With Incident Tuberculosis in HIV-Infected Patients Initiating Antiretroviral Therapy in Multinational Case-Cohort Study.Journal of acquired immune deficiency syndromes (1999) · 2017Trial
- Inflammation and Change in Body Weight With Antiretroviral Therapy Initiation in a Multinational Cohort of HIV-Infected Adults.The Journal of infectious diseases · 2016Trial
- Microbial product translocation and mortality in adults hospitalised with HIV-associated tuberculosis: a prospective observational cohort study.Research square · 2026Article
- A Systematic Review and Meta-analysis on Innovative Approaches in Tuberculosis Diagnosis: Challenges and Future Directions.International journal of MCH and AIDS · 2026Review
- Clinical characteristics of active tuberculosis with pulmonary thromboembolism.BMC pulmonary medicine · 2025Article
- Histopathological Analysis of Lipopolysaccharide-Induced Liver Inflammation and Thrombus Formation in Mice: The Protective Effects of Aspirin.Current issues in molecular biology · 2024Article
- Early on-treatment plasma interleukin-18 as a promising indicator for long-term virological response in patients with HIV-1 infection.Frontiers in medicine · 2023Article
- C-Reactive Protein as a Screening Test for Tuberculosis in People Living with HIV in Southern India: A Cross-Sectional, Observational Study.Journal of clinical medicine · 2022Article
- Clinical predictors of pulmonary tuberculosis among South African adults with HIV.EClinicalMedicine · 2022Article
- Prediction of Treatment Outcome with Inflammatory Biomarkers after 2 Months of Therapy in Pulmonary Tuberculosis Patients: Preliminary Results.Pathogens (Basel, Switzerland) · 2021Article
- C-reactive protein as a screening test for HIV-associated pulmonary tuberculosis prior to antiretroviral therapy in South Africa.AIDS (London, England) · 2018Article
- Correlates of tuberculosis risk: predictive biomarkers for progression to active tuberculosis.The European respiratory journal · 2016Review
- Sex-Related Differences in Inflammatory and Immune Activation Markers Before and After Combined Antiretroviral Therapy Initiation.Journal of acquired immune deficiency syndromes (1999) · 2016Article
- Continued Elevation of Interleukin-18 and Interferon-γ After Initiation of Antiretroviral Therapy and Clinical Failure in a Diverse Multicountry Human Immunodeficiency Virus Cohort.Open forum infectious diseases · 2016Article
Corrections and comments
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Authors and funding
23 authors at 15 institutions in 9 countries.
Funding
Abstract
objectiveThe association between pre-antiretroviral (ART) inflammation and immune activation and risk for incident tuberculosis (TB) after ART initiation among adults is uncertain.
designNested case-control study (n = 332) within ACTG PEARLS trial of three ART regimens among 1571 HIV-infected, treatment-naïve adults in 9 countries. We compared cases (participants with incident TB diagnosed by 96 weeks) to a random sample of controls (participants who did not develop TB, stratified by country and treatment arm).
methodsWe measured pre-ART C-reactive protein (CRP), EndoCab IgM, ferritin, interferon gamma (IFN-γ), interleukin 6 (IL-6), interferon gamma-inducible protein 10 (IP-10), lipopolysaccharide (LPS), soluble CD14 (sCD14), tumor necrosis factor alpha (TNF-α), and CD4/DR+/38+ and CD8/DR+/38+ T cells. Markers were defined according to established cutoff definitions when available, 75th percentile of measured values when not, and detectable versus undetectable for LPS. Using logistic regression, we measured associations between biomarkers and incident TB, adjusting for age, sex, study site, treatment arm, baseline CD4 and log10 viral load. We assessed the discriminatory value of biomarkers using receiver operating characteristic (ROC) analysis.
resultsSeventy-seven persons (4.9%) developed incident TB during follow-up. Elevated baseline CRP (aOR 3.25, 95% CI: 1.55-6.81) and IP-10 (aOR 1.89, 95% CI: 1.05-3.39), detectable plasma LPS (aOR 2.39, 95% CI: 1.13-5.06), and the established TB risk factors anemia and hypoalbuminemia were independently associated with incident TB. In ROC analysis, CRP, albumin, and LPS improved discrimination only modestly for TB risk when added to baseline routine patient characteristics including CD4 count, body mass index, and prior TB.
conclusionIncident TB occurs commonly after ART initiation. Although associated with higher post-ART TB risk, baseline CRP, IP-10, and LPS add limited value to routine patient characteristics in discriminating who develops active TB. Besides determining ideal cutoffs for these biomarkers, additional biomarkers should be sought that predict TB disease in ART initiators.
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