How to manage a patient with TB (tuberculosis) lymphadenitis (scrofula) and a positive HIV (human immunodeficiency virus) screening?

Management of TB Lymphadenitis (Scrofula) with HIV Co-infection

Immediately initiate standard four-drug anti-tuberculosis therapy (isoniazid, rifampin, pyrazinamide, and ethambutol) with directly observed therapy (DOT), and evaluate for concurrent antiretroviral therapy (ART) initiation, as prompt treatment of both diseases significantly reduces mortality and prevents disease transmission. 1

Immediate TB Treatment Initiation

Start anti-TB therapy immediately upon diagnosis without waiting for culture results or HIV staging. 1

• Use the standard 6-month regimen: 2 months intensive phase with isoniazid, rifampin, pyrazinamide, and ethambutol, followed by 4 months continuation phase with isoniazid and rifampin 1, 2, 3
• Implement DOT for all doses to ensure adherence and prevent drug resistance 1
• Obtain baseline drug susceptibility testing on all initial isolates 2
• TB lymphadenitis requires the same treatment duration as pulmonary TB in HIV-infected patients 3

HIV Assessment and ART Timing

Initiate ART in all HIV-infected TB patients regardless of CD4 count, with timing based on immunosuppression severity. 3

Timing Algorithm:

• CD4 <50 cells/mm³: Start ART within 2 weeks of beginning TB treatment 3
• CD4 ≥50 cells/mm³: Start ART within 2-8 weeks of beginning TB treatment 1, 3
• Already on ART: Continue current regimen but adjust for drug interactions 1

Rationale for Early ART:

Early ART initiation improves survival and reduces mortality, particularly in severely immunosuppressed patients, though it increases risk of immune reconstitution inflammatory syndrome (IRIS) 3, 4

Managing Drug Interactions

The choice of ART regimen depends critically on whether rifampin can be used, as rifampin has severe interactions with protease inhibitors and NNRTIs. 1

If Patient NOT Yet on ART:

Option 1 (Preferred): Rifampin-based TB regimen + Efavirenz-based ART

• Use standard rifampin-based TB treatment 1
• Combine with efavirenz (NNRTI-based ART) at standard dosing 1, 3
• Efavirenz is preferred over nevirapine due to better outcomes with rifampin 3, 4

Option 2: Rifabutin-based TB regimen + Protease inhibitor-based ART

• Substitute rifabutin for rifampin in TB regimen 1
• Use 2-month intensive phase: isoniazid, rifabutin, pyrazinamide, ethambutol daily or daily for 2 weeks then twice weekly for 6 weeks 1
• Continue 4-month phase: isoniazid and rifabutin daily or twice weekly 1
• Can combine with protease inhibitor-based ART 1

Option 3: Non-rifamycin TB regimen + Any ART

• Use 9-month regimen: isoniazid, streptomycin, pyrazinamide, ethambutol for 2 months, then isoniazid and streptomycin for 7 months 1
• Reserved for patients with rifamycin intolerance or contraindications 1

If Patient Already on Protease Inhibitor or NNRTI:

Do not use rifampin with protease inhibitors or NNRTIs due to severe drug interactions that reduce antiretroviral efficacy. 1

• Switch to rifabutin-based TB regimen 1
• Alternatively, use non-rifamycin TB regimen 1
• If switching from rifampin to allow ART initiation, wait 2 weeks after last rifampin dose before starting protease inhibitors or NNRTIs, as rifampin's enzyme induction persists 1

Monitoring and Follow-up

Clinical Monitoring:

• Assess for TB symptoms monthly: fever, night sweats, lymph node changes 1
• Monitor weight monthly to adjust medication doses 3
• Evaluate for paradoxical worsening of lymphadenopathy (TB-IRIS), especially 2-8 weeks after ART initiation 1, 5, 4

Laboratory Monitoring:

• Obtain sputum or lymph node cultures monthly until negative (if accessible) 2
• Check CD4 count and HIV viral load every 3 months 1
• Baseline and periodic liver function tests, especially with risk factors for hepatotoxicity 3, 4
• Visual acuity testing if using ethambutol 3

Managing TB-IRIS (Paradoxical Reaction)

TB-IRIS presents as worsening or new lymphadenopathy, fever, or constitutional symptoms 2-8 weeks after starting ART, despite appropriate TB treatment. 1, 5, 4

Diagnostic Approach:

• First, exclude other causes: TB treatment failure, drug resistance, new opportunistic infections, or medication side effects 4
• Obtain lymph node biopsy and culture to rule out drug-resistant TB or alternative diagnoses 5, 4
• If cultures remain negative and clinical picture consistent, diagnose TB-IRIS 5, 4

Management:

• Continue both TB treatment and ART - do not stop either regimen 1, 5
• For severe symptoms: Consider short-term corticosteroids (prednisone) to suppress enhanced immune response 1, 4
• Most cases resolve without changing antimicrobial therapy 1, 5

Critical Pitfalls to Avoid

Do not delay TB treatment while awaiting HIV staging or ART planning - TB treatment must start immediately as delays increase mortality 1

Do not use rifampin with protease inhibitors or NNRTIs - this combination causes treatment failure due to severe drug interactions 1

Do not treat TB with single-drug therapy or inadequate regimens - this rapidly creates drug resistance 2, 6

Do not assume worsening lymphadenopathy after ART initiation is always IRIS - always exclude drug-resistant TB, treatment failure, and new infections first 5, 4

Do not use nevirapine with rifampin without careful monitoring - nevirapine concentrations are frequently subtherapeutic during lead-in dosing, leading to virological failure 4

Coordination of Care

Management requires consultation with experts in both TB and HIV disease due to complexity and serious public health consequences of mismanagement. 1

• Coordinate between TB control programs and HIV/AIDS programs 1
• Report TB case to local health department as required 1
• Ensure patient has access to medications, social support, and nutritional services 1
• Consider respiratory isolation if pulmonary involvement suspected until non-infectious 1