Trends in C-Reactive Protein, D-Dimer, and Fibrinogen during Therapy for HIV-Associated Multidrug-Resistant Tuberculosis

Am J Trop Med Hyg. 2018 Nov;99(5):1336-1341. doi: 10.4269/ajtmh.18-0322.

Abstract

HIV-positive adults on treatment for multi drug-resistant tuberculosis (MDR-TB) experience high mortality. Biomarkers of HIV/MDR-TB treatment response may enable earlier treatment modifications that improve outcomes. To determine whether changes in C-reactive protein (CRP), D-dimer, and fibrinogen were associated with treatment outcome among those with HIV/MDR-TB coinfection, we studied 20 HIV-positive participants for the first 16 weeks of MDR-TB therapy. Serum CRP, fibrinogen, and D-dimer were measured at baseline and serially while on treatment. At baseline, all biomarkers were elevated above normal levels, with median CRP 86.15 mg/L (interquartile range [IQR] 29.25-149.32), D-dimer 0.85 µg/mL (IQR 0.34-1.80), and fibrinogen 4.11 g/L (IQR 3.75-6.31). C-reactive protein decreased significantly within 10 days of treatment initiation and fibrinogen within 28 days; D-dimer did not change significantly. Five (25%) participants died after a median of 32 days. Older age (median age of 38y among survivors and 54y among deceased, P = 0.008) and higher baseline fibrinogen (3.86 g/L among survivors and 6.37 g/L among deceased, P = 0.02) were significantly associated with death. After adjusting for other measured variables, higher CRP concentrations at the beginning of each measurement interval were significantly associated with a higher risk of death during that interval. Trends in fibrinogen and CRP may be useful for evaluating early response to treatment among individuals with HIV/MDR-TB coinfection.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Age Factors
  • Antitubercular Agents / therapeutic use*
  • Biomarkers / blood
  • C-Reactive Protein / analysis*
  • CD4 Lymphocyte Count
  • Female
  • Fibrin Fibrinogen Degradation Products / analysis*
  • Fibrinogen / analysis*
  • HIV / isolation & purification
  • HIV Infections / blood
  • HIV Infections / microbiology*
  • HIV Infections / mortality
  • Humans
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / drug effects
  • Risk Factors
  • Treatment Outcome
  • Tuberculosis, Multidrug-Resistant / blood
  • Tuberculosis, Multidrug-Resistant / drug therapy*
  • Tuberculosis, Multidrug-Resistant / virology

Substances

  • Antitubercular Agents
  • Biomarkers
  • Fibrin Fibrinogen Degradation Products
  • fibrin fragment D
  • Fibrinogen
  • C-Reactive Protein