Low IFN-γ plus high TNF-α in cerebrospinal fluid (CSF) may predict tuberculous meningitis immune reconstitution inflammatory syndrome (IRIS) in people with HIV and thus offer guidance on whether to start or defer antiretroviral therapy (ART) in HIV-positive people with tuberculous meningitis.
Tuberculous meningitis IRIS poses a high risk of life-threatening neurologic complications in people with TB who start ART. Researchers studied antiretroviral-naive people in South Africa with tuberculous meningitis who started TB treatment plus prednisone and 2 weeks later started ART. They compared clinical and lab findings in people who did and did not have subsequent tuberculous meningitis IRIS.
IRIS developed with severe inflammation in 16 of 34 people (47%). Two of these people died. Patients with IRIS had higher CSF neutrophil counts than those without IRIS (median 50 versus 3 cells × 10(6)/L, P = 0.02).
Mycobacterium tuberculosis could be cultured from 15 people with IRIS (94%) compared with 6 people without IRIS (33%) when tuberculous meningitis was diagnosed. A positive M tuberculosis culture raised the IRIS risk more than 9 times (relative risk 9.3, 95% confidence interval [CI] 1.4 to 62.2).
High TNF-α in CSF combined with low IFN-γ levels at meningitis diagnosis predicted tuberculous meningitis IRIS (area under the curve 0.91, 95% CI 0.53 to 0.99).
The researchers note that the high tuberculous meningitis IRIS incidence in their study was “striking” since all patients were taking prednisone when they began ART; previous research found reduced mortality from tuberculous meningitis and pericarditis in people taking corticosteroids.
The authors propose that “the combination of CSF IFN-γ and TNF-α concentrations may predict tuberculous meningitis-IRIS and thereby be a means to individualize patients to early or deferred ART.”
Source: Suzaan Marais, Graeme Meintjes, Dominique J. Pepper, Lori E. Dodd, Charlotte Schutz, Zahiera Ismail, Katalin A. Wilkinson, Robert J. Wilkinson. Frequency, severity, and prediction of tuberculous meningitis immune reconstitution inflammatory syndrome. Clinical Infectious Diseases. 2013; 56: 450-460.
Source: IAS