What is the next step in managing a 41-year-old female with Human Immunodeficiency Virus (HIV) on antiretroviral therapy (ART) and recently started on anti-tuberculosis (TB) therapy, who presents with a neck mass and fever, and has a lymph node biopsy showing granulomatous inflammation consistent with Immune Reconstitution Inflammatory Syndrome (IRIS)?

Management of Immune Reconstitution Inflammatory Syndrome (IRIS) in HIV-TB Co-infection

The most appropriate next step in managing this patient with TB-IRIS is to start NSAIDs (option D) as the first-line treatment for moderate symptoms of immune reconstitution inflammatory syndrome. 1

Understanding the Clinical Presentation

This 41-year-old female presents with classic features of TB-IRIS:

• Known HIV infection on antiretroviral therapy
• Recently started anti-TB treatment
• Development of new symptoms (neck mass and fever)
• Lymph node biopsy showing granulomatous inflammation

These findings are consistent with paradoxical TB-IRIS, which occurs when the recovering immune system mounts an inflammatory response against tuberculosis antigens after starting antiretroviral therapy.

Management Algorithm for TB-IRIS

Step 1: Confirm IRIS and Rule Out Alternative Diagnoses

• Ensure this is not treatment failure due to drug resistance
• Verify there are no new opportunistic infections
• Confirm temporal relationship with ART initiation

Step 2: Determine Severity and Initiate Treatment

• For mild to moderate IRIS (as in this case):

  • Start with NSAIDs such as ibuprofen for symptomatic relief 1
  • Continue both antiretroviral therapy and anti-TB medications 2, 1

• For severe IRIS (not present in this case):

  • Consider corticosteroids (prednisone 0.5-1.0 mg/kg/day) 1
  • Duration typically 4-8 weeks with gradual taper 2

Why NSAIDs Are the Correct Choice

The CDC/NIH/IDSA guidelines specifically recommend: "Persons who develop moderate to severe symptoms typical of IRIS during ART should receive initial treatment with nonsteroidal anti-inflammatory agents (CIII)" 2. This patient's presentation with lymphadenopathy and fever without evidence of severe disease (such as respiratory distress, CNS involvement, or hemodynamic instability) makes NSAIDs the appropriate first-line therapy.

Why Other Options Are Not Appropriate

• Option A (Hold antiretroviral therapy): Discontinuing ART is generally not recommended unless there is life-threatening IRIS, particularly with CNS involvement 2, 1. Guidelines recommend continuing ART in most cases of IRIS 2.

• Option B (Excisional lymph node biopsy): The patient has already had a lymph node biopsy showing granulomatous inflammation consistent with TB. Another biopsy would not change management and would delay appropriate treatment 1.

• Option C (Add 5th anti-TB drug): Adding additional anti-TB medications is only indicated when there is concern for drug-resistant TB, not for IRIS 2. There is no evidence suggesting drug resistance in this case.

Monitoring and Follow-up

• Assess response to NSAIDs within 1-2 weeks
• If symptoms worsen or do not improve, consider corticosteroids (prednisone 20-40 mg daily for 4-8 weeks) 2, 1
• Continue regular monitoring of both HIV and TB treatment response

Important Caveat

If the patient develops signs of severe IRIS (especially neurological deterioration, respiratory distress, or significant systemic symptoms), promptly escalate to corticosteroid therapy 1. The Clinical Infectious Diseases journal recommends prednisone 1.25 mg/kg/day for severe TB-IRIS to reduce the need for hospitalization or surgical procedures 1.