By Richard R. Watkins, MD, MS, FACP

Division of Infectious Diseases, Akron General Medical Center, Akron, OH; Associate Professor of Internal Medicine, Northeast Ohio Medical University, Rootstown, OH

Dr. Watkins reports no financial relationships relevant to this field of study.

SYNOPSIS: A retrospective, observational, single-center study found immunocompromised patients are at increased risk for neurologic sequelae from HSV meningitis and likely benefit from antiviral therapy. There is no benefit to antiviral therapy in immunocompetent individuals.

SOURCE: Noska A, et al. The role of antiviral therapy in immunocompromised patients with herpes simplex virus meningitis. Clin Infect Dis. 2015;60:237-242.

Herpes simplex virus (HSV) is a very common cause of viral meningitis in adults. It occurs in approximately 30% of women and 10% of men at the time of primary genital acquisition, although many patients report no history of genital lesions. The vast majority of HSV meningitis in adults is due to HSV-2 and most cases of encephalitis are caused by HSV-1. While clinical practice guidelines recommend IV acyclovir for HSV encephalitis, similar data and recommendations for antiviral therapy in HSV meningitis are limited. Therefore, Noska and colleagues sought to determine if antiviral therapy has an impact on the clinical course of HSV meningitis and if there are differences between immunocompetent and immunocompromised patients.

The study was a retrospective observational one from a single institution that evaluated all patients with a positive cerebral spinal fluid (CSF) sample for HSV-1 or HSV-2 between July 2000 and November 2012. Patients were classified as immunocompromised if they had any of the following: HIV with a CD4 count < 500 cells/μL; diabetes mellitus; alcohol dependence; malignancy; severe malnutrition; or receiving steroids. Neurologic outcomes were determined by chart review. All cases had outpatient follow up with a primary care physician, an infectious diseases physician and/or a neurologist.

A total of 63 episodes of HSV CNS infection in 53 patients were identified. Of these, 42 were meningitis including 15 in immunocompromised patients. The median age was 35 years and 65% were women. Among the 15 immunocompromised patients, 3 were treated with supportive care only and all developed neurologic sequelae (2 with chronic headaches and 1 had paresthesias of the hands and discoordination); 3 received oral antiviral therapy (median duration, 7 days) and all recovered completely; and 9 received a combination of intravenous (IV) and oral antiviral therapy, with 2 developing neurologic sequelae (1 with paresthesias of the hands and 1 with left arm pain). Two immunocompromised patients had recurrences and both developed neurologic sequelae (paresthesias in one and headaches and discoordination and paresthesias in the other). No CNS sequelae occurred in the immunocompetent group. The association between treatment and outcome was significant in the immunocompromised group (P < 0.05) but not in the immunocompetent group (P = 1.0). In other words, treating immunocompromised patients with antiviral therapy was associated with significantly fewer neurologic sequelae. Interesting, patients with HSV meningitis had higher CSF white blood cell (WBC) counts compared to those with encephalitis (median, 328 cells/μL vs. 50 cells/μL, respectively) and in one episode of HSV meningitis and 3 of HSV encephalitis the CSF WBC count was normal (< 5 cells/μL).

COMMENTARY

HSV meningitis is frequently encountered in clinical practice, yet there is a lack of strong evidence for its management. Therefore, the study by Noska and colleagues is welcomed because it adds to this body of evidence and helps inform medical decision making. Their main finding was that short course antiviral therapy seems to help immunocompromised patients by reducing neurologic sequelae but had no benefits for immunocompetent patients. In their short discussion they do not offer any possible explanation for this result and recommend treating immunocompromised patients with HSV meningitis with a 7 to 10 day course of antiviral therapy. Although this approach seems reasonable, the limitations of the study reduce its impact. These include a retrospective design that could have been influenced by confounding factors, a small sample, and that it was conducted at a single center which lessens its applicability to other settings. Moreover, differences in the routes of antiviral therapy could have influenced the results i.e. it is unclear if IV therapy led to better outcomes compared to oral therapy. Finally, the lack of benefit from antiviral therapy seen in immunocompetent patients is not surprising since these patients have a very low risk of neurologic sequelae at baseline.

Despite the informative study by Noska and colleagues, it will likely take a prospective randomized clinical trial with a large sample size to determine the optimal management of HSV meningitis. In the interim, I suggest treating immunocompromised patients with oral antiviral therapy (e.g., valacyclovir) for 7 days and using clinical judgment to decide about treating immunocompetent patients. For instance, antiviral therapy may be considered for immunocompetent patients who are severely ill or not improving after several days of supportive/conservative treatment.