Acyclovir Not Beneficial With HSV Oropharyngeal Reactivation

Pre-emptive use of acyclovir does not seem to reduce the duration of mechanical ventilation in critically ill patients with herpes simplex virus (HSV) oropharyngeal reactivation, according to results of a study published in JAMA Network Internal Medicine.

With 50% to 80% of healthy adults living with the infection, HSV is the species of Herpesviridae that is most responsible for infections in humans, which follow a relapsing and remitting pattern. Mechanical ventilation is strongly associated with reactivation of HSV in patients with oropharyngeal HSV who are immunocompetent; reactivation occurs in 20% to 50% of patients receiving mechanical ventilation.

Previous studies have suggested that HSV detection in the lower respiratory tract and HSV bronchopneumonitis are associated with poorer outcomes. However, the role of HSV reactivation on morbidity and mortality in patients in the intensive care unit (ICU) requiring mechanical ventilation and whether treatment with acyclovir could improve prognosis remains unknown. Therefore, this double-blind, placebo-controlled, randomized clinical trial determined whether pre-emptive treatment with intravenous acyclovir reduced the duration of mechanical ventilation in patients with HSV oropharyngeal reactivation (ClinicalTrials.gov Identifier: NCT02152358).

Between 2014 and 2018, a total of 238 patients (aged >18 years) were included from 16 French ICUs. Inclusion criteria included receipt of ≥96 hours of mechanical ventilation and a prediction of a minimum of 48 hours or more of such therapy and positive results for HSV reactivation via oropharyngeal swab testing. Patients were randomly assigned to receive either intravenous acyclovir 5 mg/kg 3 times daily for 14 days or a matching placebo (n=119 patients each). The primary endpoint was ventilator-free days from randomization to day 60. Secondary outcomes included mortality at 60 days, mechanical ventilation duration, and occurrence of HSV bronchopneumonitis. The main analyses were performed on an intention-to-treat basis.

Results suggested that routine use of acyclovir in this setting did not affect outcomes differently from placebo. The median number of ventilator-free days at day 60 was 35 days for the acyclovir group and 36 days for the placebo group (P =.17). On day 60, results demonstrated that 26 (22%) patients in the acyclovir group and 39 (33%) patients in the control group had died (P =.06). Median mechanical ventilation duration for day 60 survivors was 17 days for acyclovir recipients and 14 days for control patients (P =.89).

Both groups had similar adverse event frequency (28% in the acyclovir group and 23% in the placebo group; P =.40). Notably, acute renal failure affected 3 patients in the acyclovir group and 2 patients in the control group. A total of 4 patients in the acyclovir group and no patients in the placebo group discontinued study drug because of treatment-related adverse events.

Overall, the study authors concluded that, “It appears that for ICU patients with HSV reactivation in the throat while receiving mechanical ventilation for 96 hours or more, acyclovir, 5 mg/kg, 3 times daily compared with placebo was unable to increase the day 60 number of ventilator-free days.”

They added, “Our study results show that preemptive acyclovir administration, compared with placebo for mechanically ventilated patients with oropharyngeal HSV reactivation, was not associated with shorter mechanical ventilation durations, as assessed by the number of ventilator-free days.”

Reference

Luyt CE, Forel JM, Hajage D, et al. Acyclovir for mechanically ventilated patients with herpes simplex virus oropharyngeal reactivation: a randomized clinical trial [published online December 16, 2019]. JAMA Intern Med. doi:10.1001/jamainternmed.2019.5713