Is Tenofovir alafenamide (tenofovir alafenamide) effective for treating leukocytoclastic vasculitis, particularly in a patient with a history of HIV?

Tenofovir Alafenamide and Leukocytoclastic Vasculitis

Tenofovir alafenamide should be immediately discontinued if leukocytoclastic vasculitis develops, as tenofovir is a documented cause of drug-induced leukocytoclastic vasculitis, and drug withdrawal alone is typically sufficient for resolution without requiring immunosuppressive therapy. 1, 2

Evidence for Tenofovir as a Causative Agent

The critical issue here is that tenofovir itself can cause leukocytoclastic vasculitis (LCV), not treat it. A case report documented tenofovir-induced LCV in a patient with chronic hepatitis B who developed non-blanchable erythematous to violaceous papules and targetoid patches on the lower extremities one month after starting tenofovir. The rash resolved completely within days after replacing tenofovir with entecavir. 2

While this case involved tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) is a prodrug that delivers the same active moiety (tenofovir) to tissues, making it biologically plausible that TAF could trigger the same vasculitic reaction. 3, 4

Management Algorithm for Drug-Induced LCV

Step 1: Immediate Drug Discontinuation

• Stop tenofovir alafenamide immediately upon clinical suspicion of LCV, as this is the primary treatment and often sufficient for complete resolution. 1
• Drug withdrawal alone typically induces prompt resolution without requiring immunosuppressive therapy. 1

Step 2: Assess Disease Severity

For mild cutaneous disease only:

• Observation after drug discontinuation is appropriate. 1
• Most cases resolve spontaneously within weeks. 5

For severe disease with skin necrosis or systemic involvement:

• Add systemic corticosteroids: prednisolone 1 mg/kg/day (maximum 60 mg/day). 1
• Do not use cyclophosphamide or rituximab, as these are reserved for ANCA-associated vasculitis, not drug-induced LCV. 1

Step 3: Alternative HIV Therapy Selection

For the HIV-positive patient, immediate transition to an alternative antiretroviral regimen is essential:

Recommended alternatives without tenofovir:

• Dolutegravir/abacavir/lamivudine (if HLA-B*5701 negative). 6
• Raltegravir plus abacavir/lamivudine. 6
• Dolutegravir/lamivudine (if HIV RNA <500,000 copies/mL, no HBV coinfection, and no lamivudine resistance). 6

Critical caveat: If the patient has hepatitis B coinfection, tenofovir-containing regimens are typically preferred for dual HIV/HBV treatment. 6 In this scenario, switching to entecavir for HBV (as done in the published case) plus a tenofovir-free HIV regimen would be necessary. 2

Diagnostic Clues to Confirm Drug-Induced Etiology

Look for these features that distinguish drug-induced from idiopathic vasculitis:

• High-titer MPO-ANCA positivity or dual MPO and PR3 ANCA positivity. 1
• Discordance between ANCA type by immunofluorescence versus ELISA. 1
• Positive ANA and antihistone antibodies. 1
• Temporal relationship: onset within weeks to months of drug initiation. 2, 7

Critical Pitfall to Avoid

Do not confuse drug-induced LCV with ANCA-associated vasculitis (AAV). Drug-induced LCV may present with positive ANCA serology, leading to misdiagnosis as AAV and inappropriate treatment with cyclophosphamide or rituximab. 1 The key distinguishing feature is that drug-induced LCV resolves with drug withdrawal alone, whereas AAV requires immunosuppression. 1

Monitoring After Drug Discontinuation

• Assess for rash resolution within days to weeks. 2
• If switching from TAF to another antiretroviral regimen, monitor HIV RNA every 4-6 weeks until undetectable. 6
• Monitor renal function and urinalysis, as tenofovir can cause proximal tubular dysfunction that may coexist with vasculitis. 6, 8