# Valaciclovir therapy for secondary suppression of immune response to herpesviruses: An exploratory study

## TL;DR

This study tested if valaciclovir could reduce immune response to herpesviruses in older adults, but found no effect on immune response or health.

## Contribution

The study explores a novel approach to potentially improve immune function by suppressing herpesvirus-specific immunity in older individuals.

## Key findings

- Valaciclovir treatment did not reduce CMV or EBV-specific immune responses in older donors.
- Treatment had no impact on physical or mental quality of life in participants.
- Alternative therapies or longer treatment durations may be needed to suppress herpesvirus-specific immunity.

## Abstract

Herpesviruses establish a state of persistent infection which is suppressed by sustained virus-specific immune control. The magnitude of this immune response can increase with age and lead to attrition of immune reserve against other pathogens. Approaches which suppress herpesvirus-specific immunity may therefore have the potential to improve general immune function. Anti-retroviral therapy for HIV leads to a reduction in HIV viral antigen and has been shown to mediate a secondary attenuation of the HIV-specific immune response. As such, we assessed if treatment with valaciclovir could suppress the immune response against cytomegalovirus and Epstein Barr Virus in donors aged >65 years. Medication was given at 3 different doses up to a maximum of 4gm/day for 6 months and humoral and cellular profiles were assessed over 12 months. Anti-viral therapy did not impact on the magnitude or phenotype of the humoral or cellular virus-specific immune response during the study period. Treatment also had no impact of physical or mental quality of life assessment. These data show that valaciclovir treatment, at this dose and treatment duration, does not attenuate the CMV or EBV-specific immune response in this age group.

Cytomegalovirus (CMV) is a herpesvirus that infects most people during their lifetime. The virus can never be eradicated after infection and its replication must be suppressed by sustained immune pressure throughout life. This virus-specific immune response becomes very large in older people and may limit the ability of the immune system to make effective immune responses against other infections. Here we performed a clinical trial in which we treated healthy older people for six months with the antiviral drug valaciclovir to see if suppression of CMV would subsequently attenuate the CMV-specific immune response and improve well being. This approach did not lead to a reduction in CMV-specific immune response and had no impact on health measurements. As such, alternative approaches such as extended duration therapy or alternative anti-viral drugs are required in future studies to assess potential suppression of herpesvirus-specific immunity.