The timing of his presentation is consistent with the immune reconstitution inflammatory syndrome (IRIS) (median 48 days), the return of a robust immune response resulting from treatment of the HIV that “unmasks” a pre-existing infection that appears like a new acute infection. This presentation is common with tuberculosis, which may present as a much more acute pulmonary illness resembling bacterial pneumonia. He had an indeterminate result on interferon-γ release assay (IGRA) because of an inadequate response to the positive control, which was the result of immunocompromise at the time of presentation; additionally, the results of IGRA testing are a poor indicator of active tuberculosis infection. He should begin four-drug antituberculous therapy while results of culture and susceptibility testing are pending. Nucleic acid amplification testing of the specimen may give information on the identification of the organisms and even the possibility of rifamycin resistance. Initial empiric treatment for tuberculosis should include a rifamycin as one of the four drugs, but rifabutin is often preferred over rifampin in patients with HIV because of fewer drug-drug interactions between rifabutin and antiretrovirals, including dolutegravir.
If this patient does have active tuberculosis, treatment is needed urgently; culture results may take weeks, so waiting would be inappropriate.
Antiretrovirals should not be stopped when IRIS occurs. Therapy should be continued while providing treatment for the newly diagnosed infection.
Prednisone can be added if IRIS is life threatening or involves the pericardium or central nervous system. None of these is the case in this patient; giving glucocorticoids without a known diagnosis increases the risk of worsening an infection that is not being directly treated.
Reactivation of latent tuberculosis is also significantly increased in HIV infection, even without a decreased CD4 cell count. Tuberculosis is also more likely to present in extrapulmonary sites or with an atypical chest radiograph. Tuberculosis treatment in HIV must consider interactions of rifamycins with many antiretrovirals.
Immune reconstitution inflammatory syndrome in HIV and TB