Should hydroxychloroquine be discontinued during an active herpes simplex virus (HSV) or varicella‑zoster virus (VZV) infection, and what is the recommended antiviral and prophylactic management?

Hydroxychloroquine Management During Active Herpes Infections

Hydroxychloroquine does not need to be discontinued during active HSV or VZV infections; instead, initiate appropriate antiviral therapy immediately with acyclovir, valacyclovir, or famciclovir, and reserve hydroxychloroquine discontinuation only for severe disseminated or invasive herpes infections in immunocompromised patients where temporary reduction of all immunosuppression is warranted. 1, 2

Treatment Algorithm for Active Herpes Infections

Initial Assessment and Antiviral Selection

• For uncomplicated HSV or localized VZV (shingles): Start oral acyclovir 800 mg five times daily, valacyclovir 1000 mg three times daily, or famciclovir 500 mg three times daily for 7-10 days, continuing until all lesions have completely scabbed. 1, 2

• Hydroxychloroquine continuation is appropriate in most cases of uncomplicated herpes infections, as the primary treatment is antiviral therapy, not immunosuppression modification. 1, 2

When to Escalate to IV Therapy and Consider Hydroxychloroquine Discontinuation

Intravenous acyclovir 10 mg/kg every 8 hours is mandatory for:

• Disseminated herpes zoster (lesions in >3 dermatomes or visceral involvement) 1, 2
• Severe immunocompromised patients with active chemotherapy or significant immune dysfunction 1, 2
• CNS complications (encephalitis, meningitis) 2
• Complicated ocular disease 2
• Hemorrhagic or necrotic lesions suggesting severe disease 2

In these severe cases, temporary reduction or discontinuation of hydroxychloroquine should be considered alongside other immunosuppressive medications, but only when clinically feasible. 1, 2

Prophylaxis Considerations

• Universal antiviral prophylaxis is not recommended for patients on hydroxychloroquine alone. 1

• Consider prophylaxis with acyclovir 400 mg twice daily or valacyclovir 500 mg daily only in patients with:

  • History of recurrent HSV/VZV reactivations 1
  • Concomitant high-dose corticosteroids (>40 mg prednisone daily) 1, 2
  • Additional T-cell depleting agents (rituximab, alemtuzumab, fludarabine) 1

Critical Monitoring Parameters

• Continue antiviral therapy until all lesions have completely scabbed, not just for an arbitrary 7-day period—this is the key clinical endpoint. 1, 2

• Monitor renal function at baseline and weekly during IV acyclovir therapy, with dose adjustments for creatinine clearance <50 mL/min. 2

• If lesions fail to improve within 7-10 days, suspect acyclovir resistance and obtain viral culture with susceptibility testing; switch to foscarnet 40 mg/kg IV every 8 hours if resistance is confirmed. 2, 3

Common Pitfalls to Avoid

• Do not discontinue hydroxychloroquine reflexively for every herpes infection—this is unnecessary for uncomplicated cases and may destabilize the underlying autoimmune condition. 1, 2

• Do not use topical antivirals as they are substantially less effective than systemic therapy. 1, 2

• Do not stop antiviral therapy at exactly 7 days if lesions are still forming or have not completely scabbed—short-course therapy designed for genital herpes is inadequate for VZV infection. 2

• Avoid corticosteroids during active herpes infections as they can increase risk of dissemination and severe disease, particularly in immunocompromised patients. 2

Re-introduction of Hydroxychloroquine

Resume hydroxychloroquine only after:

• All vesicular lesions have crusted 2
• Fever has resolved 2
• Clinical improvement is documented on antiviral therapy 2

This approach prioritizes controlling the acute viral infection with appropriate antivirals while maintaining disease-modifying therapy (hydroxychloroquine) whenever safely possible, reserving immunosuppression modification only for severe, life-threatening presentations.