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

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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.

Tenforde 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 ACTG PEARLS and NWCS 319 Study Group. 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. PLoS One. 2015 Feb 26;10(2):e0117424. doi: 10.1371/journal.pone.0117424. eCollection 2015. doi: 10.1371/journal.pone.0117424.
  • Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD
  • University of California Davis Medical Center, Sacramento, CA
  • Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand
  • Asociación Civil Impacta Salud y Educación (IMPACTA) Peru Clinical Trials Unit, Lima, Peru
  • Nelson Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa
  • Instituto de Pesquisa Clínica Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
  • National AIDS Research Institute, Pune, India
  • Hospital Nossa Senhora da Conceição, Porto Alegre, Brazil
  • Les Centres Groupe Haïtien d'Etude du Sarcome de Kaposi et des Infections Opportunites (GHESKIO), Port-Au-Prince, Haiti
  • University of Witwatersrand, Johannesburg, South Africa
  • University of North Carolina Project, Kamuzu Central Hospital, Lilongwe, Malawi
  • Malawi College of Medicine-Johns Hopkins University Research Project, Blantyre, Malawi
  • University of Zimbabwe, Harare, Zimbabwe
  • Y.R. Gaitonde Centre for AIDS Research and Education (YRG CARE), Chennai, India
  • University of Colorado Denver School of Medicine, Aurora, CO