Background: Although the etiology of multiple sclerosis (MS) remains uncertain, clinical, epidemiological, and laboratory findings suggest that environmental factors may be involved in the disease.

Objective: This study was undertaken in order to investigate the possible relation of human herpesvirus-6 (HHV-6) in relapsing-remitting MS (RRMS).

Methods: A one-year follow-up study was performed analyzing serum samples of 63 patients with RRMS and 63 healthy blood donors (HBD) by a quantitative real time PCR, to measure HHV-6 prevalence and viral load. Clinical data (starting age and EDSS increase) were collected.

Results: (i) We found 25.4% of RRMS patients with at least one positive serum sample along the one year follow-up. (ii) 19.1% of RRMS samples in relapse had HHV-6 active infection vs. 7.9% of RRMS samples in remission. (iii) We only found variant A. (iv) RRMS patients with HHV-6 active replication initiated the disease 1.9 years earlier, and they had a higher EDSS increase.

Conclusions: A higher HHV-6A frequency of active infection seems to be related with the exacerbations in a subset of RRMS patients. Regarding the relationship between HHV-6A active infection and the clinical data in RRMS patients, further investigations are needed.