Acyclovir ineffective for extending ventilator-free days in reactivated HSV ICU patients

Takeaway

• Preemptive acyclovir 5 mg/kg tid q14d does not increase ventilator-free days at day 60 in mechanically ventilated (MV) ICU patients experiencing oropharyngeal herpes simplex virus (HSV) reactivation.
• Related editorial. 

Why this matters

• Although preemptive acyclovir in MV patients with oropharyngeal HSV reactivation may potentially improve OS, its use is not currently recommended. 

Key results

• 238 assessable patients (119 acyclovir, 119 placebo).
• Primary endpoint was median ventilator-free days at day 60: 
  • 35 days with acyclovir vs 36 days with placebo.
  • P=.17 for between-group comparison.
• Secondary endpoint was 60-day mortality:
  • 22% (26) acyclovir vs 33% (39) placebo.
  • HR, 0.61 (P=.047).
• Post hoc analyses, mortality on day 90:
  • 28% (33) acyclovir vs 34% (41) placebo (P=.26).
• Per-protocol analysis, median ventilator-free days:
  • 31 days with acyclovir vs 34 with placebo (P=.42).
• Mortality:
  • 23% (26) acyclovir vs 34% (39) placebo (P=.09).

Study design

• Double-blind, placebo-controlled, multicentre, interventional study assessing effectiveness of preemptive acyclovir in MV HSV-reactivated French patients, February 2014-February 2018.
• Funding: Direction de la Recherche Clinique et du Développement, French Ministry of Health.

Limitations

• No serial monitoring of HSV shedding in respiratory tract secretions.
• Nongeneralisable.
• Extracorporeal membrane oxygenation support, renal replacement therapy limited to acyclovir recipients. 
• Small sample size.