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.

TitleC-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.
Publication TypeJournal Article
Year of Publication2015
AuthorsTenforde MW, Gupte N, Dowdy DW, Asmuth DM, Balagopal A, Pollard RB, Sugandhavesa P, Lama JR, Pillay S, Cardoso SW, Pawar J, Santos B, Riviere C, Mwelase N, Kanyama C, Kumwenda J, Hakim JG, Kumarasamy N, Bollinger R, Semba RD, Campbell TB, Gupta A
Corporate AuthorsACTG PEARLS and NWCS 319 Study Group
JournalPLoS One
Volume10
Issue2
Paginatione0117424
Date Published2015
ISSN1932-6203
KeywordsAdult, AIDS-Related Opportunistic Infections, Anti-Retroviral Agents, C-Reactive Protein, Chemokine CXCL10, Developing Countries, Female, Humans, Incidence, Lipopolysaccharides, Male, Risk, Tuberculosis
Abstract

OBJECTIVE: The association between pre-antiretroviral (ART) inflammation and immune activation and risk for incident tuberculosis (TB) after ART initiation among adults is uncertain.

DESIGN: Nested 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).

METHODS: We 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.

RESULTS: Seventy-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.

CONCLUSION: Incident 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.

DOI10.1371/journal.pone.0117424
Alternate JournalPLoS ONE
PubMed ID25719208
PubMed Central IDPMC4342263
Grant ListAI069450 / AI / NIAID NIH HHS / United States
AI68636 / AI / NIAID NIH HHS / United States
R01 AI45462 / AI / NIAID NIH HHS / United States
R01 DA016078 / DA / NIDA NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069423 / AI / NIAID NIH HHS / United States
UM1 AI069463 / AI / NIAID NIH HHS / United States
UM1 AI069518 / AI / NIAID NIH HHS / United States