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Background. Concomitant genital herpes and papillomavirus infections increase a risk for the manifestations of cervical neoplasia. A search for possible medicaments that accelerate the regression of this pathology is being continued. Specific drugs that completely eliminate human papillomavirus (HPV) and herpes simplex virus (HSV) have not been designed today; work to study alternative antiviral and immune modulatory agents is still in progress. The Russian antiviral and immunomodulatory drug allokin-alpha is of interest.
Objective. To evaluate the efficiency of combination therapy using allokin-alpha for genital diseases concurrent with HPV and HSV infections, to compare the medical therapy with allokin-alpha versus destructive treatment without this drug, and to assess the tolerability and safety on the basis of an analysis of adverse events.
Design. A comparative randomized controlled clinical trial.
Subject and methods. After obtaining informed consent, 60 reproductive-aged patients with HPV and HSV infection and cytological and colposcopic signs of flat and exophytic condylomas and low-grade cervical intraepithelial neoplasia (CIN I) were randomized to two groups: 1) 31 patients were given allokin-alpha injections (n = 6) 1 mg/day subcutaneously every other day during argon plasma ablation (APA) treatment; 2) 29 patients received conventional APA treatment (acyclovir 1 g daily for 7 days). All the patients included in the study underwent colposcopy, bacterioscopy, PCR diagnosis of infections (with HPV, HSVII-I, cytomegalovirus (CMV), M. genitalium, or Chl. trachomatis) in the cervical canal epithelial scrape. The follow-up was 6 months. During the investigation, the patients kept a diary where they wrote down the specific features of the course of the infections and therapy-related side effects, their magnitude and duration. Diary data were assessed and PAP test, colposcopy, PCR test for HPV and HSV types I-II, and bacterioscopy were carried out 3 and 6 months after cervical APA. During their participation in the investigation, all the patients used barrier methods of contraception.
Results. Since colposcopy is a somewhat subjective test to evaluate the efficiency of therapy with the basic emphasis laid on the data of PAP test and PCR for HPV and HSV. Comparison of 3- and 6-month follow-up results revealed a significant difference in the number of cases of CU epithelial normalization in Groups 1 and 2 patients, which was evidenced by the PAP test in 22 (77.4%) and 19 (65.5%) patients after 3 months and in 28 (90.3%) and 20 (68.9%) patients after 6 months, respectively (P < 0.05). In Groups 1 and 2, PCR for HPV became negative in 17 (54.8%) and 12 (41.1%) cases following 3 months and in 24 (77.4%) and 17 (58.6%) cases following 6 months, respectively (P < 0.05). In these groups, 6-month colposcopy showed positive cervical changes in 29 (93.5%) patients in Group 1 and in 26 (89.6%) patients in Group 2, respectively (P > 0.05). During the follow-up, there were significantly fewer HSV infection recurrences in Group 1. None of the patients in the groups had any serious adverse reactions.
Conclusion. Allokin-alpha enhances the efficiency of treatment for CINI and exophytic cervical condylomas concurrent with HPV and recurrent HSV infections, favors their regression, and declines the number of herpesvirus infection recurrences. The drug is safe and well tolerated in the treatment using the above regimen.