What is the recommended treatment for lymphadenopathy in patients with Human Immunodeficiency Virus (HIV)?

Management of Lymphadenopathy in HIV Patients

The treatment of lymphadenopathy in HIV patients depends entirely on the underlying cause: benign persistent generalized lymphadenopathy (PGL) requires only antiretroviral therapy (ART) optimization, while pathologic lymphadenopathy from opportunistic infections or malignancies requires specific antimicrobial or chemotherapeutic treatment in addition to ART. 1

Initial Diagnostic Approach

The first critical step is distinguishing benign PGL from pathologic lymphadenopathy, as this determines the entire treatment pathway 1:

• Benign PGL characteristics: Symmetrical, generalized adenopathy (≥2 non-contiguous sites) without constitutional symptoms, typically in patients with CD4 >200 cells/μL 1
• Pathologic features requiring investigation: Localized lymphadenopathy, hepatosplenomegaly, constitutional symptoms (fever, night sweats, weight loss >10%), or rapidly enlarging nodes 1

Mandatory Initial Workup

Every HIV patient with significant lymphadenopathy requires 1:

• CD4+ T-lymphocyte count and HIV viral load
• Complete blood count with platelets
• Tuberculin skin test (PPD ≥5 mm is positive in HIV patients) 1
• Syphilis serology
• Contrast-enhanced CT chest/abdomen/pelvis if pathologic features present 1

Critical caveat: FDG-PET/CT has higher sensitivity for extranodal disease but produces frequent false-positives in HIV patients due to opportunistic infections and immune deficiency-related lymphoid hyperplasia—FDG-avid lesions should be re-biopsied if used to escalate treatment 2, 1

Treatment Based on CD4 Count and Etiology

CD4 >500 cells/μL: Benign PGL Most Likely

• No specific treatment required beyond ART optimization 1
• Initiate or optimize ART immediately to achieve viral suppression 1, 3
• Preferred first-line ART regimens 3:
  • Bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC)
  • Dolutegravir plus tenofovir/emtricitabine or lamivudine
  • Dolutegravir/lamivudine (if HIV RNA <500,000 copies/mL, no HBV co-infection)

CD4 200-500 cells/μL: Increased Risk of TB and HIV-Related Symptoms

• Tuberculosis becomes more common in this range 1
• If TB diagnosed: Start standard anti-tuberculous therapy immediately and continue ART throughout TB treatment 1
• ART timing with TB: Initiate within 2-8 weeks of starting TB treatment if CD4 ≥50 cells/μL; within 2 weeks if CD4 <50 cells/μL 3

CD4 <200 cells/μL: High Risk for Opportunistic Infections and Lymphomas

This requires comprehensive evaluation in a specialty setting 1. Prophylaxis is mandatory 2, 1:

• PCP prophylaxis strongly recommended (trimethoprim-sulfamethoxazole preferred) 2, 1
• Antiviral prophylaxis with acyclovir or valacyclovir for patients with herpes simplex or varicella zoster history 2, 1
• Antifungal prophylaxis with fluconazole for CD4 <100 cells/μL, especially with anticipated prolonged neutropenia 2

Treatment of HIV-Associated Lymphomas

If biopsy confirms lymphoma, treatment requires both chemotherapy and continued ART 2:

Hodgkin Lymphoma

• ABVD regimen preferred (doxorubicin/bleomycin/vinblastine/dacarbazine) due to lower toxicity profile 2, 1
• Stanford V is an alternative with good results 2
• Continue ART throughout chemotherapy with attention to drug-drug interactions 2

Diffuse Large B-Cell Lymphoma (DLBCL)

• Full-dose intensive chemotherapy with rituximab for CD20-positive disease 1
• R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) is standard
• ART must be continued and optimized during chemotherapy 2

Critical management principle: A multidisciplinary approach including an HIV specialist is mandatory to prevent drug-drug interactions between chemotherapy, ART, and supportive medications 2. Specific interaction checking available at www.hiv-druginteractions.org and www.cancer-druginteractions.org 2

ART Optimization During Treatment

All patients with HIV-related lymphadenopathy should receive effective ART, including those with preserved immune function 2:

• ART should be initiated immediately and continued during any chemotherapy to ensure sustained viral suppression 2
• Multiple prospective studies demonstrate improved chemotherapy tolerability, immune recovery, and patient outcomes with concurrent ART 2
• ART can be modified to avoid drug-drug interactions without compromising HIV control 2

Expected Viral Load Response

• Measure viral load 4-6 weeks after starting ART 2
• HIV RNA suppression may take up to 24 weeks, faster with integrase inhibitor-based regimens 2
• Once HIV RNA <50 copies/mL, monitor every 3 months until suppressed ≥1 year, then every 6 months 2

Common Pitfalls to Avoid

1. Delaying lymph node biopsy when pathologic features present—localized adenopathy, hepatosplenomegaly, or constitutional symptoms mandate tissue diagnosis 1
2. Stopping ART during chemotherapy—this worsens outcomes and immune recovery 2
3. Failing to provide PCP prophylaxis during chemotherapy even if CD4 >200 cells/μL—chemotherapy with prednisone causes profound CD4 decline 2
4. Interpreting PET/CT without considering opportunistic infections—both infections and HIV itself cause FDG-avid lymphadenopathy 2, 1
5. Delaying ART initiation—immediate ART (within 7 days of diagnosis) reduces mortality by 63% even in patients with CD4 >500 cells/μL 4