Treating reactivated EBV, HHV-6, HHV-7 infections in children with Autism Spectrum disorder associated with genetic folate cycle disruptions: Outcomes after Valacyclovir, Valganciclovir and Artesunate

Immune dysfunction causes the reactivation of herpesviruses in children with autism spectrum disorder (ASD) associated with the genetic folate cycle deficiency (GFCDs). The aim – to investigate the efficacy of valaciclovir, valganciclovir, and artesunate in reactivated Epstein-Barr virus (EBV), herpes virus type 6 (HHV-6) and herpes virus type 7 (HHV-7) infections in children with ASD. The treatment group consisted of 225 children aged 2 to 9 years who had GFCDs and ASD. The diagnosis of EBV, HHV-6, and HHV-7 reactivations was made by blood leukocyte PCR. Valacyclovir (500-1000 mg twice per day), valganciclovir (225-450mg twice per day), and artesunate (25-50mg twice a day) were prescribed for 3 months. The control group (no antiviral treatment) included 52 children who were comparable in age and diagnosis. Valacyclovir treatment achieved undetectable EBV DNA in 39% of cases. Valganciclovir and artesunate performed complete response rates of 47 and 62%, respectively (p<0.05; Z<Z_0.05). HHV-6 DNA was undetectable in 29% of valacyclovir-treated patients. Valganciclovir and artesunate achieved complete response rates of 32 and 57%, respectively (p<0.05; Z<Z_0.05). HHV-7 DNA was not detected in 24% of valacyclovir-treated patients, but in 35 and 44%, respectively (p<0.05, Z<Z_0.05) in valganciclovir and artesunate groups. There was an association found between negative PCR results and normalized S-100 protein and neuron-specific enolase serum concentrations. Antiviral treatments disrupted the natural course of reactivated EBV, HHV-6, and HHV-7 infections in ASD children, exerting a neuroprotective effect, with artesunate being the most effective option and EBV - the most sensitive to antiviral drugs.