Цель. Изучение механизма противовирусного действия и оценка клинической эффективности, безопасности и переносимости терапии препаратом Фортепрен у пациентов с хронической рецидивирующей герпесвирусной инфекцией генитальной локализации. Материалы и методы. Клинические исследования проходил лекарственный препарат Фортепрен (натрия полипренилфосфат) раствор для инъекций, 4 мг/мл, который вводили пациентам, прошедшим базовый курс препарата Ацикловир-Акри для снятия острой фазы заболевания. Исследование проводили на 80 пациентах мужского и женского пола, отобранных в процессе скрининга с подтвержденным диагнозом хроническая рецидивирующая герпесвирусная инфекция генитальной локализации (ХРГВИ). Было сформировано 2 группы. Пациентам 1 группы (экспериментальной) Фортепрен в дозе 2 мл (8 мг) вводили внутримышечно на стадии ремиссии трехкратно с интервалом в 21 день на 3±2, 24±2 и 45±2 сутки после окончания 10-дневного базового курса лечения острой фазы заболевания с применением препарата ацикловир таблетки по 400 мг — 13±2, 34±2 и 55±2 день от начала исследования. Пациентам 2 группы (контрольной) раствор плацебо в объеме 2 мл вводили внутримышечно на стадии ремиссии трехкратно на 3±2, 24±2 и 45±2 сутки после окончания базового курса лечения острой фазы заболевания с применением препарата ацикловир таблетки по 400 мг — 13±2, 34±2 и 55±2 день от начала исследования. Для оценки эффективности применения препарата Фортепрен использовали такие критерии как: увеличение продолжительности межрецидивного периода, уменьшение частоты рецидивов за весь период наблюдения; снижение выраженности рецидивов, оцененное в баллах, изменение иммунологических показателей по динамике изменения продукции основных цитокинов. Результаты. В 1 группе пациентов межрецидивный период за весь период проведения исследования статистически значимо увеличился с 29,36±2,16 до 42,98±3,29 суток. В то время как во 2 группе изменения этого показателя не отмечено. Соответственно у пациентов 1 группы отмечено статистически достоверное сокращение частоты рецидивов ХРГВИ с 3,03±0,02 до начала лечения до 1,94±0,19 во время лечения при отсутствии снижения частоты рецидивов в контроле. Оценка в баллах выраженности рецидивов ХРГВИ у пациентов группы 1 указывает на эффективность данной схемы лечения. Сумма баллов средних значений балла выраженности признаков ХРГВИ статистически достоверно снизилась в 1 группе с 7,36±0,35 баллов на 1 визите до начала лечения до 4,75±0,35 баллов во время лечения. Во 2 группе изменений не отмечено. Уровень лейкоцитарного вирус-индуцированного интерферона (ЛВИ—ИФН) у пациентов экспериментальной группы повысился к завершению клинического исследования с 36 до 64% по сравнению с контрольной группой, в которой не наблюдалось прироста титров ЛВИ-ИФН. Оценка продукции ИФНα, ИФНγ, ИЛ-10, ИЛ-12p40, ИЛ-12p70, ИЛ-15, ИЛ-2, ИЛ-4, МИФ-1α, ФНОα показала увеличение их количества к завершению исследования у пациентов, получавших препарат Фортепрен, по сравнению с контрольной группой. Заключение. Показана эффективность применения препарата Фортепрен в дозе 2 мл (8 мг) при внутримышечном введении пациентам с хронической рецидивирующей герпесвирусной инфекцией генитальной локализации на стадии ремиссии трехкратно с интервалом в 21 день на 3±2, 24±2 и 45±2 сутки после окончания 10-дневного базового курса лечения острой фазы заболевания с применением препарата ацикловир.

The group of female reproductive tract tumors includes cancers of corpus uteri, ovary, cervix, vulva and vagina (the last three are associated with HPV). Among the large group of sexually transmitted infections (STIs) there are only six infections, which subject to registration in the official statistical data in Russia: syphilis, gonorrhea, trichomoniasis, chlamydia, urogenital herpes and anogenital warts (AGWs). Occurrence of AGWs in 95–100% of cases caused by HPV types 6 and 11. Objectives: our aim was to determine the prevalence of HPV-associated diseases (cervical cancer and anogenital warts) in the structure of female reproductive tract tumors and STIs in recent years in Moscow, and to compare it with the prevalence in population of Russia. Methods: we analyzed retrospective data with diagnostic codes related to cancers of corpus uteri, ovary, cervix, vulva and vagina from the official statistic of cancer register using incidence and mortality rates between January 2007 and December 2015 in Russia and Moscow. We also analyzed retrospective data of STIs (incl. syphilis, gonorrhea, trichomoniasis, chlamydia, urogenital herpes and AGWs) incidence rates between January 2003 and December 2015. Results: average rate of cervical cancer incidence among the female reproductive tract tumors accounted for 23.7% in Moscow (29.8% in Russia). Average rate of cervical cancer mortality among the female reproductive tract tumors accounted for 24.1% in Moscow (28.3% in Russia). The rate of AGWs in the STIs structure (for both sexes) in Moscow increased from 11.5% in 2003 to 25.7% in 2015 (the maximum was 31.0% in 2014). The highest rate of AGWs was detected in the age group 15–17 years (up to 59.8% in 2012), followed by 18–29 years (up to 37.3% in 2014). The rate of AGWs was 11.7% among all STIs (in both sexes) in Russia in 2015. Conclusion: HPV-associated diseases (cervical cancer and AGWs) take up a significant place in the structure of female reproductive tract tumors and STIs. And in the structure of the STI for Moscow, AGWs moved from the 5th (in 2003) to the 1st (in 2015) ranked place, surpassing syphilis, gonorrhea, trichomoniasis and chlamydia. The effective prevention of HPV-infection would be able to improve the situation.

Aim. The study of the mechanism of antiviral action and evaluation of the clinical efficacy, safety and tolerability of therapy with Fortepren® in patients with chronic recurrent herpesvirus infection of genital localization (CRHVI). Materials and methods. Clinical studies were carried out of a drug Fortepren® (0.4% sodium polyprenyl phosphate solution), which was administered to patients who underwent a basic therapeutic course of the drug Acyclovir-Acry® to relieve the acute phase of the disease. The study was performed on 80 male and female patients selected during the screening with a confirmed diagnosis of CRHVI. Two groups were formed. Patients of group 1 (experimental) were intramuscularly injected with Fortepren® at a dose of 2 ml (8 mg) three times at intervals of 21 days by 3 ± 2, 24 ± 2 and 45 ± 2 days following the 10-day basic course of treatment of the acute phase of diseases with the use of the acyclovir tablets of 400 mg - 13 ± 2, 34 ± 2 and 55 ± 2 days from the beginning of the study. Patients of the 2nd group (control) were intramuscularly injected with placebo solution at a volume of 2 ml instead of Fortepren®. To evaluate Fortepren® efficacy, the following criteria were used: increase in the duration of the inter-recessive period, a decrease in the frequency of relapses over the entire observation period; decrease in the severity of relapses, estimated in points, changes in immunological parameters according to the dynamics of changes in the production of the main cytokines. Results. In patients treated with Fortepren®, the inter-recurrence period for the entire study period increased statistically from 29.36 ± 2.16 to 42.98 ± 3.29 days, while in the control group this indicator have not changed. Accordingly, in patients treated with Fortepren®, a statistically significant reduction in the incidence of recurrence of CRHVI from 3.03 ± 0.02 before treatment to 1.94 ± 0.19 was observed during treatment in the absence of a decrease in the frequency of relapses in the control. Evaluation of the severity of CRHVI relapses in patients treated with Fortepren® indicates the efficacy of this protocol. The sum of the scores of the mean values of CRHVI symptoms signs was statistically significantly decreased in the group 1 from 7.36 ± 0.35 points at the 1 st visit before the start of treatment to 4.75 ± 0.35 points during the treatment. No changes were seen in the control group. The level of leukocyte virus-induced interferon (LVI-IFN) in the patients of the group 1 increased from 36% to 64% in the end of the clinical trial compared to the control group, in which the increase in LVI-IFN titers was not observed. To further justify the possibility of increasing the immune response of cells, establishing possible mechanisms that determine the efficacy of treatment for CRHVI with Fortepren®, evaluation of the production of IFNz, IFNy, IL-10, IL-12p40, IL-12p70, IL-15, IL-2, IL-4, MIF-Fz, TNFа was made. In the of the study levels of all these cytokines was increased in patients treated with Fortepren® compared with the control group. Conclusion. The efficacy of using Fortepren® in a dose of 2 ml (8 mg) with intramuscular administration to patients with chronic recurrent herpesviral infection of genital localization at the stage of remission three times with an interval of 21 days by 3 ± 2, 24 ± 2 and 45 ± 2 days after the end of 10 day basic course of treatment of the acute phase of the disease with the use of the drug acyclovir.

Aim. The study of the mechanism of antiviral action and evaluation of the clinical efficacy, safety and tolerability of therapy with Fortepren ® in patients with chronic recurrent herpesvirus infection of genital localization (CRHVI). Materials and methods. Clinical studies were carried out of a drug Fortepren ® (0.4% sodium polyprenyl phosphate solution), which was administered to patients who underwent a basic therapeutic course of the drug Acyclovir-Acry® to relieve the acute phase of the disease. The study was performed on 80 male and female patients selected during the screening with a confirmed diagnosis of CRHVI. Two groups were formed. Patients of group 1 (experimental) were intramuscularly injected with Fortepren ® at a dose of 2 ml (8 mg) three times at intervals of 21 days by 3 ± 2, 24 ± 2 and 45 ± 2 days following the 10-day basic course of treatment of the acute phase of diseases with the use of the acyclovir tablets of 400 mg - 13 ± 2, 34 ± 2 and 55 ± 2 days from the beginning of the study. Patients of the 2nd group (control) were intramuscularly injected with placebo solution at a volume of 2 ml instead of Fortepren ® . To evaluate Fortepren ® efficacy, the following criteria were used: increase in the duration of the inter-recessive period, a decrease in the frequency of relapses over the entire observation period; decrease in the severity of relapses, estimated in points, changes in immunological parameters according to the dynamics of changes in the production of the main cytokines. Results. In patients treated with Fortepren ® , the inter-recurrence period for the entire study period increased statistically from 29.36 ± 2.16 to 42.98 ± 3.29 days, while in the control group this indicator have not changed. Accordingly, in patients treated with Fortepren ® , a statistically significant reduction in the incidence of recurrence of CRHVI from 3.03 ± 0.02 before treatment to 1.94 ± 0.19 was observed during treatment in the absence of a decrease in the frequency of relapses in the control. Evaluation of the severity of CRHVI relapses in patients treated with Fortepren ® indicates the efficacy of this protocol. The sum of the scores of the mean values of CRHVI symptoms signs was statistically significantly decreased in the group 1 from 7.36 ± 0.35 points at the 1 st visit before the start of treatment to 4.75 ± 0.35 points during the treatment. No changes were seen in the control group. The level of leukocyte virus-induced interferon (LVI-IFN) in the patients of the group 1 increased from 36% to 64% in the end of the clinical trial compared to the control group, in which the increase in LVI-IFN titers was not observed. To further justify the possibility of increasing the immune response of cells, establishing possible mechanisms that determine the efficacy of treatment for CRHVI with Fortepren®, evaluation of the production of IFNz, IFNy, IL-10, IL-12p40, IL-12p70, IL-15, IL-2, IL-4, MIF-Fz, TNFа was made. In the of the study levels of all these cytokines was increased in patients treated with Fortepren® compared with the control group. Conclusion. The efficacy of using Fortepren ® in a dose of 2 ml (8 mg) with intramuscular administration to patients with chronic recurrent herpesviral infection of genital localization at the stage of remission three times with an interval of 21 days by 3 ± 2, 24 ± 2 and 45 ± 2 days after the end of 10 day basic course of treatment of the acute phase of the disease with the use of the drug acyclovir.