Effect of antiviral therapy on the outcome of mechanically ventilated patients with herpes simplex virus type 1 in bronchoalveolar lavage fluid: a retrospective cohort study

Background: Herpes simplex virus type 1 (HSV-1) is frequently detected in the bronchoalveolar lavage fluid (BAL) of mechanically ventilated patients.

Research question: The aim of the study was to investigate whether antiviral therapy is associated with improved overall survival within 30 days.

Study design: Retrospective cohort study in 4 intensive care units (ICUs) between 01/2011 and 12/2017.

Methods: All mechanically ventilated adult patients with a respiratory tract infection with positive polymerase chain reaction testing for HSV-1 in the BAL were included. Patients already receiving antiviral agents on the day BAL was performed were excluded. We performed uni- and multivariable Cox and logistic regression modelling.

Results: Overall, 306 patients were included in the analysis. Among them, 177 patients (57.8%) received antiviral therapy (90.9% acyclovir, 6.2% ganciclovir, 2.9% both). The overall 30-day mortality rate was 42.4% (n=75) in antiviral treatment group and 50.4% (n=65) in the control group. The adjusted hazard ratio (HR) for the primary outcome was 0.62 (95% confidence interval (CI) 0.44-0.87, p=0.005), indicating better overall survival within 30 days for the antiviral-treated group than for the untreated group. This benefit was also present in the subgroup of patients without immunosuppression (n=246; adjusted HR 0.53, 95% CI 0.36-0.78, p=0.001). Overall, the median lengths of hospital stay (31 vs. 24 days, p=0.002) and ICU stay (24 vs. 17 days, p<0.001), as well as the duration of mechanical ventilation (18 vs. 11 days, p<0.001), were longer for patients with therapy. No evidence for the treatment-related deterioration of renal function was observed.

Interpretation: These data suggest that detection of HSV-1 in the BAL of mechanically ventilated patients may be of clinical significance and that specific antiviral treatment may improve clinical outcomes. However, this needs to be proven in multicentre randomized controlled trials before implementation into the clinical routine.