COMPARATIVE STUDY OF THE EFFECTIVENESS OF VALACYCLOVIR, VALGANCICLOVIR AND ARTESUNATE IN CHRONIC REACTIVATED HHV-6- AND HHV-7 INFECTIONS ASSOCIATED WITH CHRONIC FATIGUE SYNDROME / MYALGIC ENCEPHALOMYELITIS
DOI:
https://doi.org/10.32689/2663-0672-2021-2-10Keywords:
polymerase chain reaction, herpes viruses, blood leukocytes, virostatic therapy, resistance to antiviral drugsAbstract
Formulation of the problem. The association of chronic fatigue syndrome with reactivated HHV-6- and HHV-7 infections has been established and the benefits of using antiviral chemotherapeutics in such cases have been demonstrated. Although chronic reactivated HHV-6- and HHV-7 infections are among the most common herpesvirus infections in the current population, there are currently few clinical studies to study the effectiveness of antiviral drugs in such cases. Moreover, no comparative trials of different virostatic chemotherapeutics have been performed in the reactivation of these viral agents from latency or persistence in patients with chronic fatigue syndrome. Formulation of the purpose of the study. The aim is to compare the efficacy of valacyclovir, valganciclovir and artesunate in chronic reactivated HHV-6- and HHV-7 - infections associated with chronic fatigue syndrome / myalgic encephalomyelitis. Analysis of recent research and publications. The results of a number of controlled clinical trials indicate the reactivation of herpesviruses in patients with chronic fatigue syndrome, which is confirmed by positive PCR results of blood leukocytes Materials and methods of research. Between 2015 and 2021, 192 cases of reactivated HHV-7 infection associated with chronic fatigue syndrome / myalgic encephalomyelitis were identified in adult patients aged 19 to 42 years. The diagnosis of reactivated herpesvirus infection was made by PCR of blood leukocytes with species-specific primers HHV-6 and HHV-7 (Institute of Neurosurgery, National Academy of Medical Sciences of Ukraine, Department of Neurobiochemistry). Valacyclovir was administered at a dose of 3000 mg per day, valganciclovir - 900 mg / day, and artesunate - 100 mg / day daily orally for 3 consecutive months. The control group consisted of 63 patients with chronic fatigue syndrome who were not taking antiviral drugs. Carried out monthly monitoring of PCR of blood leukocytes. The probability of differences in the obtained results was evaluated by the parametric Student's T-test with the calculation of the confidence probability p and the non-parametric criterion - the number of Z signs by Urbach Yu.V. Research results. Elimination of HHV-6 and HHV-7 DNA from blood leukocytes with valacyclovir was achieved after the first month of treatment in 26% and 23%, the second – 34% and 28%, and the third – 37% and 34% of cases, respectively. Negative PCR results of blood leukocytes with species-specific primers HHV-6 and HHV-7 when using valganciclovir were obtained in 35% and 33% of cases after the first, in 44% and 39% of cases – after the second, in 48% and 45% - after the third month therapy, respectively. In contrast, in the artesunate subgroup, HHV-6 and HHV-7 DNA was removed from blood leukocytes after the first month of treatment in 44% and 41%, the second in 57% and 53%, and the third in 68% and 63%. % of cases, respectively. Differences in the efficacy of the three antiviral drugs used were statistically significant at all study endpoints (p <0.05; Z <Z0.05). In any case, there remained many patients who showed resistance to all tested therapeutic strategies, indicating the need for higher doses of virostatic drugs, longer courses of treatment and / or combination regimens. Conclusions and prospects for further research. Artesunate is the most effective in the treatment of chronic reactivated HHV-6 and HHV-7 infections associated with chronic fatigue syndrome / myalgic encephalomyelitis in adult patients compared to valganciclovir, which demonstrated moderate antiviral activity and valacic acid efficacy. of the studied drugs.
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