A 31-year-old man presents to the emergency department for fever, malaise, and cough. For the last week, his cough has been progressively worsening, and he has been noticing blood in his sputum. He denies any recent travel or sick contacts and infrequently smokes cigarettes. Approximately 5 weeks ago, he presented with similar symptoms and was found to have a right upper lobe lung infiltrate, a CD4 count of 40/mm^3, and an HIV viral load of 115,000 copies/mL. He was appropriately treated and discharged home. Four weeks after initiation of treatment, his CD4 count was over 400/mm^3 and HIV viral load was negligible. His temperature today is 102°F (38.9°C), blood pressure is 130/90 mmHg, pulse is 100/min, and respirations are 20/min. A radiograph of the chest demonstrates new nodules in the left upper lobe and hilar adenopathy. Which of the following is the most appropriate next step in management?
Continue current anti-retroviral treatment, antimicrobial, and anti-tuberculoid therapies
Determine drug sensitivities against the patient’s pulmonary infection
Discontinue antimicrobial treatment
Obtain a D-dimer level
Continue current anti-retroviral treatment, antimicrobial, and anti-tuberculoid therapies
This patient with recently diagnosed HIV and tuberculosis infection (upper lung lobe infiltrate) is presenting with worsening symptoms after being appropriately treated. Worsening of symptoms after initiation of these therapies is concerning for immune reconstitution inflammatory syndrome (IRIS), which is managed by continuing current combined antiretroviral medications, antibiotics for opportunistic infections and symptom management.

IRIS describes a paradoxical worsening of a patient's underlying infection after initiating antiretroviral therapy for patients with HIV. IRIS can also occur in HIV-uninfected patients with tuberculosis or leprosy who are started on antimycobacterial treatment. The pathogenesis of IRIS is unclear, but in patients with HIV, antiretroviral therapy increases the amount of CD4+ T-helper cells, which can lead to an exaggerated inflammatory response (e.g., increased cytokine release) towards the infection. Thus, there is a paradoxical worsening of the infection symptoms. When patients have a paradoxical worsening of their symptoms in the setting of starting their antiretroviral therapy, the therapy should be continued with symptomatic management (acetaminophen for fever).

Nelson et al review IRIS. They note it is seen in patients with HIV. They recommend antiretroviral therapy and antibiotics for bacterial infections.

Incorrect Answers:
Answer B: Determining drug sensitivities against the patient’s pulmonary infection would be of low diagnostic utility since IRIS best explains his current clinical presentation.

Answer C: Discontinuing antimicrobial treatment would not be appropriate since the patient has findings concerning for tuberculosis (upper lobe lung infiltrate), and lack of treatment can lead to progression of his infection.

Answer D: Obtaining a D-dimer level is only indicated in low-risk patients for pulmonary embolism by Wells criteria.

Answer E: Starting high-dose glucocorticoid treatment and discontinuing antiretroviral therapy would not be appropriate since discontinuing his antiretroviral therapy would not control his HIV infection, which would place him at greater risk of acquiring opportunistic infections. Corticosteroid use is part of symptom management as it decreases the inflammatory response.

Bullet Summary:
Immune reconstitution inflammatory syndrome (IRIS) can result in worsening of infectious symptoms and is managed by continuing antiviral therapy with symptomatic treatment.