Intravenous acyclovir shortened the duration of herpes simplex virus shedding among mechanically ventilated patients, a new study found, but the dose and duration tested weren’t sufficient to totally suppress oropharyngeal HSV reactivation and shedding.
Intravenous acyclovir significantly reduced herpes simplex virus oropharyngeal reactivation in medically ventilated patients, but throat shedding was still detected in a third of patients, according to a recent research letter.
The ancillary study, published in JAMA Network Open, included 130 adults in intensive care units in Paris and Marseille, France, who were part of the Preemptive Treatment for Herpesviridae randomized clinical trial.
The parent trial didn’t support routine preemptive use of acyclovir among mechanically ventilated patients with HSV oropharyngeal reactivation because the treatment didn’t increase the number of ventilator-free days compared with placebo. The ancillary study evaluated the impact of acyclovir on oropharyngeal HSV reactivation.
Participants were mechanically ventilated, had oropharyngeal HSV reactivation and were randomized with 66 receiving 5 mg/kg of avyclovir and 64 receiving a placebo three times a day for 14 days.
“This analysis of a randomized clinical trial found that intravenous acyclovir at a dosing of 15 mg/kg/d for 14 days was effective in decreasing the duration of HSV oropharyngeal shedding compared with placebo among patients mechanically ventilated for 96 hours or more,” the study authors, led by Charles-Edouard Luyt MD, PhD, wrote. “However, throat HSV shedding was still detected among one-third of patients after 14 days of antiviral treatment.”
Oropharyngeal swabs were collected on days 7, 14 and 21.
The incidence of HSV-negative oropharyngeal swabs was significantly higher in the acyclovir group at day 21 compared with the placebo group (67.3% [95% CI, 49.0%-81.0%] vs 36.8% [95% CI, 23.0%-51.0%] respectively; P = .008). Subdistribution hazard ratios for acyclovir vs placebo obtained from the Fine-Gray model for HSV negative swab, extubation, and death were 2.50 (95% CI, 1.42-4.39), 0.41 (95% CI, 0.17-0.96), and 0.52 (95% CI, 0.20-1.35), respectively, the authors noted.
The PTH trial showed decreased mortality but an increased duration of mechanical ventilation among patients in the acyclovir group.
“One hypothesis for the negative result of the PTH trial was the inefficacy of acyclovir to cure HSV oropharyngeal reactivation, although this drug has been shown to prevent HSV reactivation,” the authors wrote. “Although we found here that acyclovir allowed the shortening of HSV shedding duration, this dosing and duration of antiviral treatment do not appear to be sufficient to totally suppress oropharyngeal HSV reactivation and shedding among patients who are mechanically ventilated.”
Further research is needed to determine whether increased doses or duration could improve outcomes.