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Efficacy and safety of glucosaminylmuramyl dipeptide in treatment of human papillomavirus-associated diseases: a systematic review

https://doi.org/10.17749/2313-7347.2019.13.2.132-154

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Abstract

Introduction. Human papillomavirus infection (HPV-infection) remains one of the most important health problems as it significantly reduces the quality of life and stigmatizes the patients. Also, the prevalence of cervical cancer – the most severe outcome of the HPV-infection is 5 % of the global burden of cancer. Although vaccination against human papillomavirus has been proved efficient, its availability in Russia continues to be limited. Therefore, it is important to review other methods of HPV-infection control. A number of studies have confirmed the efficacy of glucosaminylmuramyl dipeptide (GMDP) in the treatment of diseases associated with HPV-infection, but no systematic evaluation of these studies has been published in the available literature.

Aim: to analyze the data on the efficacy and safety of GMDP in the treatment of diseases and conditions associated with HPVinfection.

Materials and methods. We used the PRISMA approach. The search for the relevant publications was conducted in international scientific databases: the Scientific Electronic Library, the Google Scholar, the ScienceDirect, the Cochrane Community Library, the Pubmed/MEDLINE, and clinical research registries. For this systematic analysis, only full-text publications were used. We evaluated the reliability of evidence and the methodological quality of the studies.

Results. We used the following search queries: "glucosaminyl-muramyl dipeptide", "glucosamine L'muramyl dipeptide", "H-acetylglucosaminyl-H-acetylmuramyl dipeptide", "GMDP", "Licopid" (both in Russian and English transcriptions). Based on the results of the screening, 14 full-text publications were selected. At the final stage, review articles with secondary data were excluded; also excluded were original articles published in doubtful resources and those with an unclear status of peer reviewing. This systematic analysis includes 7 publications of acceptable methodological quality. Here, we summarize the consistent conclusions derived from these reports: the addition of therapy with GMDP to local (surgical) methods increases the efficacy of treatment and the duration of remission; destruction of condylomas is more effective when combined with the course of GMDP as compared to using the local destruction alone; GMDP enhances the production of cytokines that have a direct antiviral and antiproliferative effect in HPV-infection (interleukin-1, tumor necrosis factor alpha, gamma-interferon); GMDP causes normalization of cellular and humoral immunity (T-lymphocytes, T-cytotoxic lymphocytes, B-lymphocytes, CD3+, CD4+, CD8+, CD16+, and CD72+ lymphocytes, as well as the production of serum immunoglobulins IgA, IgG, and IgM). A high safety profile of GMDP is evidenced from the absence of reports on adverse events.

Discussion. The recommendation for the inclusion of GMDP into a comprehensive treatment for HPV-infection in addition to local interventions is a strong recommendation. The differences between the Russian and international approaches can be explained by the difference in the available resources and funding. We propose to test whether using GMDP for reducing the risk of recurrent HPV-infection is beneficial in terms of pharmacoeconomics. Conclusion. The high efficacy and safety of GMDP in the combined therapy of HPV-infection has been confirmed. Further carefully designed studies on GMDP are needed.

About the Authors

A. D. Makatsariya
I.M. Sechenov First Moscow State Medical University, Health Ministry of Russian Federation
Russian Federation

Alexander D. Makatsariya – MD, PhD, Corresponding Member of RAS, Professor, Head of the Department of Obstetrics and Gynecology, Faculty of Clinical and Preventive Medicine

Researcher ID: M-5660-2016

Scopus Author ID: 6602363216



V. O. Bitsadze
I.M. Sechenov First Moscow State Medical University, Health Ministry of Russian Federation
Russian Federation
Victoria O. Bitsadze – MD, PhD, Professor RAS, Professor, Department of Obstetrics and Gynecology, Faculty of Preventive Medicine


J. Kh. Khizroeva
I.M. Sechenov First Moscow State Medical University, Health Ministry of Russian Federation
Russian Federation
Jamilya Kh. Khizroeva – MD, PhD, Professor, Department of Obstetrics and Gynecology, Faculty of Preventive Medicine


G. Kh. Vikulov
People's Friendship University of Russia
Russian Federation
George Kh. Vikulov – PhD, Director of the National Research Center for the Prevention and Treatment of Viral Infections, Leading Expert in Immunology and Infectious Diseases, IC and PCP, Assistant, Department of Infectious Diseases, Medical Institute


M. A. Gomberg
Moscow Scientific and Practical Center for Dermatovenerology and Cosmetology, Moscow Healthcare Department
Russian Federation

Mikhail A. Gomberg – MD, PhD, Professor, Chief Researcher, 

President of the STD Experts Association

Scopus Author ID: 6603854132



A. A. Khryanin
Novosibirsk State Medical University, Health Ministry of Russian Federation
Russian Federation
Alexey A. Khryanin – MD, PhD, Professor, Department of Dermatovenerology and Cosmetology; Vice President of the Society for Obstetrics, Gynecology and Dermatovenerology


References

1. Bruni L., Diaz M., Castellsague X. et al. Cervical human papillomavirus prevalence in 5 continents: meta-analysis of 1million women with normal cytological findings. J Infect Dis. 2010;202(12):1789–99. DOI: 10.1086/657321.

2. Bruni L., Barrionuevo-Rosas L., Albero G. et al. ICO/IARC information Centre on papillomavirus and cancer (HPV information Centre). Human papillomavirus and related diseases in the world. Summ Rep. 2017;19. Available at: http://www.hpvcentre.net/index.php. [Accessed: 12.03.2019].

3. Bitsadze V.O., Khamani N.M., Makatsariya N.A. Role of inosine pranobex in management of HPV-associated diseases: problems and prospective. [Mesto immunomodulyatorov v kontrole VPCh-associirovannyh zabolevanij: problemy i perspektivy]. Akusherstvo, ginekologiya i reprodukciya. 2016;10(3):76–84. (In Russ.). DOI: 10.17749/2313-7347.2016.10.2.076-084.

4. Minkina G.N. Cytological screening of the cervical cancer: from the traditional PAP-test to computer technologies. [Citologicheskij skrining raka shejki matki: ot tradicionnogo pap-testa k komp'yuternym tekhnologiyam]. Akusherstvo, ginekologiya i reprodukciya. 2017;11(1):56–63. (In Russ.). DOI: 10.17749/2313-7347.2017.11.1.056-063.

5. Plummer M., de Martel C., Vignat J. et al. Global burden of cancers attributable to infections in 2012: a synthetic analysis. Lancet Glob Health. 2016;4(9):609–16. DOI: 10.1016/S2214-109X(16)30143-7.

6. Serrano B., Brotons M., Bosch F.X., Bruni L. Epidemiology and burden of HPV-related disease. Best Pract Res Clin Obstet Gynaecol. 2018;47:14–26. DOI: 10.1016/j.bpobgyn.2017.08.006.

7. Results of the implementation of the HPV (human papillomavirus) vaccination program in the Moscow Region. [Itogi realizacii programmy vakcinoprofilaktiki virusa papillomy cheloveka v Moskovskoj oblasti]. Akusherstvo, ginekologiya i reprodukciya. 2017;11(2):75–7. (In Russ.).

8. Baranov A.A., Namazova-Baranova L.S., Tatochenko V.K. et al. Vaccine prophylaxis of diseases caused by the human papillomavirus: Federal clinical guidelines of Health Ministry of Russian Federation, Union of Pediatricians of Russia. [Vakcinoprofilaktika zabolevanij, vyzvannyh virusom papillomy cheloveka: Federal'nye klinicheskie rekomendacii MZ RF, Soyuz pediatrov Rossii]. Moskva: Pediatr, 2016. 39 s. (In Russ.).

9. Forman D., de Martel C., Lacey C.J. et al. Global burden of human papillomavirus and related diseases. Vaccine. 2012;30(Suppl 5):F12–23.

10. Sarucci M., Franco E.L., Ding L. et al. Non-vaccine-type human papillomavirus prevalence after vaccine introduction: no evidence for type replacement but evidence for cross-protection. Sex Transm Dis. 2018;45(4):260–5. DOI: 10.1097/OLQ.0000000000000731.

11. Bouvard V., Baan R., Straif K. et al. A review of human carcinogense – part B: biological agents. Lancet Oncol. 2009;10(4):321–2.

12. Khan M.J., Castle P.E., Lorincz A.T. et al. The elevated 10-year risk of cervical precancer and cancer in women with human papillomavirus (HPV) type 16 or 18 and the possible utility of type-specific HPV testing in clinical practice. J Natl Cancer Inst. 2005;97(14):1072–9. DOI: 10.1093/jnci/dji187.

13. Pett M.R., Herdman M.T., Palmer R.D. et al. Selection of cervical keratinocytes containing integrated HPV16 associates with episome loss and an endogenous antiviral response. Proc Natl Acad Sci USA. 2006;103(10):3822–7.

14. Kanodia S., Fahey L.M., Kast W.M. Mechanisms used by human papillomaviruses to escape the host immune response. Curr Cancer Drug Targets. 2007;7:79–89.

15. Kulikov A.Yu., Akimova Yu.I. The features of methodology for pharmacoeconomics analysis of vaccination. [Metodologiya farmakoekonomicheskogo analiza vakcinoprofilaktiki]. FARMAKOEKONOMIKA. Sovremennaya farmakoekonomika i farmakoepidemiologiya. 2013;6(1):4–10. (In Russ.).

16. Karaulov A.V., Blinov D.V. Prevention and treatment of diseases caused by human papillomavirus. [Profilaktika i lechenie zabolevanij, vyzyvaemyh virusom papillomy cheloveka]. Vakcinaciya. 2011;(1):37–42. (In Russ.).

17. Joura E.A., Leodolter S., Hernandez-Avila M. et al. Efficacy of a quadrivalent prophylactic human papillomavirus (types 6, 11, 16, and 18) L1 virus–like-particle vaccine against high-grade vulval and vaginal lesions: a combined analysis of three randomized clinical trials. Lancet. 2007;369:1693–702.

18. Lehtinen M., Paavonen J., Wheeler C.M. et al. Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against grade 3 or greater cervical intraepithelial neoplasia: 4-year end-of-study analysis of the randomized, double-blind PATRICIA trial. Lancet Oncol. 2012;13:89–99.

19. Villa L.L., Costa R.L., Petta C.A. et al. High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up. Br J Cancer. 2006;95:1459–66.

20. Paavonen J., Naud P., Salmeron J. et al. Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomized study in young women. Lancet. 2009;374:301–14.

21. Drolet M., Benard E., Boily M.C. et al. Population-level impact and herd effects following human papillomavirus vaccination programmes: a systematic review and meta-analysis. Lancet Infect Dis. 2015;15(5):565–80.

22. Markowitz L.E., Liu G., Hariri S. et al. Prevalence of HPV after introduction of the vaccination program in the United States. Pediatrics. 2016;137:1–9.

23. Kahn J.A., Widdice L.E., Ding L. et al. Substantial decline in vaccine type human papillomavirus (HPV) among vaccinated young women during the first 8 years after HPV vaccine introduction in a community. Clin Infect Dis. 2016;63:1281–7.

24. Tabrizi S.N., Brotherton J.M., Kaldor J.M. et al. Assessment of herd immunity and cross-protection after a human papillomavirus vaccination programme in Australia: a repeat cross-sectional study. Lancet Infect Dis. 2014;14(10):958–66.

25. Cameron R.L., Kavanagh K., Pan J. et al. Human papillomavirus prevalence and herd immunity after introduction of vaccination program, Scotland, 2009–2013. Emerg Infect Dis. 2016;22:56–64.

26. Huang S.S., Platt R., Rifas-Shiman S.L. et al. Post-PCV7 changes in colonizing pneumococcal serotypes in 16 Massachusetts communities, 2001 and 2004. Pediatrics. 2005;116:e408–13.

27. Wheeler C.M., Castellsagué X., Garland S.M. et al. Cross-protective efficacy of HPV-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by non-vaccine oncogenic HPV types: 4-year end-of-study analysis of the randomized, double-blind PATRICIA trial. Lancet Oncol. 2012;13:100–10.

28. Khryanin A.A. Is the immunotherapy of urogenital infections possible from the viewpoint of evidence-based medicine? [Vozmozhna li immunoterapiya urogenital'nyh infekcij s pozicij dokazatel'noj mediciny?] Klinicheskaya dermatologiya i venerologiya. 2017;16(3):82–8. (In Russ.).

29. Khryanin A.A. Immunomodulating therapy of sexually transmitted infections from the viewpoint of evidence-based medicine. [Immunomoduliruyushchaya terapiya infekcij, peredavaemyh polovym putem, s pozicij dokazatel'noj mediciny]. Status Praesens. 2016;(3):33–41. (In Russ.).

30. Shikunova I.A. Modern mechanism of immunomodulation. [Sovremennyj mekhanizm immunomodulyacii]. VetPharma. 2012;1–2:1–4. (In Russ.).

31. Licopid. Instructions for medical use. LS-001438. State Register of Medicines. [Likopid. Instrukciya po medicinskomu primeneniyu. LS-001438. Gosudarstvennyj Reestr Lekarstvennyh Sredstv]. Available at: http://www.grls.rosminzdrav.ru. (In Russ.). [Accessed: 22.02.2019].

32. Scott M., Nakagawa M., Moscicki A.B. Cell-mediated immune response to human papillomavirus infection. Clin Diagn Lab Immunol. 2001;8(2):209–20.

33. Khryanin A.A. How to increase the effectiveness of treatment of genital papillomavirus infection? [Kak povysit' effektivnost' terapii papillomavirusnoj infekcii genitalij?] Voprosy ginekologii, akusherstva i perinatologii. 2017;16(5):51–8. (In Russ.).

34. Order of the Ministry of Health of Russia dated February 28, 2019 N 103n «On approval of the procedure and deadlines for the development of clinical guidelines, their revision, standard clinical guidelines and requirements for their structure, composition and scientific validity of the information included in clinical guidelines». [Prikaz Minzdrava Rossii ot 28.02.2019 N 103n «Ob utverzhdenii poryadka i srokov razrabotki klinicheskih rekomendacij, ih peresmotra, tipovoj formy klinicheskih rekomendacij i trebovanij k ih strukture, sostavu i nauchnoj obosnovannosti vklyuchaemoj v klinicheskie rekomendacii informacii»]. 13 s. (In Russ.). Available at: http://www.remedium.ru/legislation/other/Prikaz_Minzdrava_RF_ ot_28_02_2019_103n_. [Accessed: 12.03.2019].

35. Turánek J., Ledvina M., Kasná A. et al. Liposomal preparations of muramyl glycopeptides as immunomodulators and adjuvants. Vaccine. 2006;24(Suppl 2):S2–90.

36. Knotigová P.T., Zyka D., Mašek J. et al. Molecular adjuvants based on nonpyrogenic lipophilic derivatives of norAbuMDP/GMDP formulated in nanoliposomes: stimulation of innate and adaptive immunity. Pharm Res. 2015;32(4):1186–99. DOI: 10.1007/s11095-014-1516-y.

37. Effenberg R., Turánek Knötigová P., Zyka D. et al. Nonpyrogenic molecular adjuvants based on norAbu-muramyldipeptide and norAbu-glucosaminyl muramyldipeptide: synthesis, molecular mechanisms of action, and biological activities in vitro and in vivo. J Med Chem. 2017;60(18):7745–63. DOI: 10.1021/acs.jmedchem.7b00593.

38. Petrova E.E., Valyakina T.I., Simonova M.A. et al. Muramyl peptides augment cytotoxic effect of tumor necrosis factor-alpha in combination with cytotoxic drugs on tumor cells. Int Immunopharmacol. 2006;6(9):1377–86.

39. Petrova E.E., Valyakina T.I., Komaleva R.L. et al. Glucosaminylmuramyl dipeptide potentiates the effects of tumor necrosis factor-alpha and cisplatin on transformed cells in vitro. Bull Exp Biol Med. 2007;143(2):251–4. DOI: 10.1007/s10517-007-0063-5.

40. Akhmatova N.K., Semenova I.B., Donenko F.V. et al. Immunomodulators of microbial origin enhance cytotoxicity of human mononuclear leukocytes and reduce metastatic progression of Lewis lung carcinoma in mice. [Mikrobnye immunomodulyatory usilivayut citotoksichnost' mononuklearnyh lejkocitov cheloveka i umen'shayut metastazirovanie legochnoj karcinomy L'yuisa u myshej]. Zhurnal mikrobiologii, epidemiologii i immunobiologii. 2006;(6):35–40. (In Russ.).

41. Petrova E.E., Simonova M.A., Komaleva R.L. et al. GMDP augments antitumor action of the CP/TNF-alpha combination in vivo. Biomed Pharmacother. 2010;64(4):240–8. DOI: 10.1016/j.biopha.2009.06.019.

42. Konorev M.R. Use of the immunopotentiator N-acetylglucosamine-N-acetylmuramyl dipeptide during triple anti-Helicobacter pylori therapy. [Primenenie immunomodulyatora N-acetilglyukozaminil-N-acetilmuramildipeptida pri provedenii trekhkomponentnoj antihelikobakternoj terapii]. Terapevticheskij arhiv. 2012;84(12):66–70. (In Russ.).

43. Konorev M.R., Andronova T.M., Matveenko M.E. Use of probiotics and probiotic-based immunomodulators as adjuvant therapy for Helicobacter pylori eradication. [Ispol'zovanie probiotikov i immunomodulyatorov na ih osnove v kachestve ad"yuvantnoj terapii pri provedenii eradikacii Helicobacter pylori]. Terapevticheskij arhiv. 2016;88(12):140–8. (In Russ.). DOI: 10.17116/terarkh20168812140-148.

44. Maiorov R.V., Derbenov D.P. The clinical economic analysis of application of immune correcting preparations to prevent respiratory infections and their complications in frequently ill children of early school age. [Kliniko-ekonomicheskij analiz primeneniya immunokorrigiruyushchih preparatov dlya profilaktiki respiratornyh infekcij i ih oslozhnenij u chasto boleyushchih detej mladshego shkol'nogo vozrasta]. Problemy social'noj gigieny, zdravoohraneniya i istorii mediciny. 2014;22(6):23–6. (In Russ.).

45. Liang Y., Wu J., Wang W. et al. Pro-endometriotic niche in endometriosis. Reprod BioMed Online. 2019;38(4):549–59.

46. Balitsky K.P., Umansky V., Tarakhovsky A. et al. Glucosaminylmuramyl dipeptide-induced changes in murine macrophage metabolism. Inter J Immunopharmacol. 1989;11(5):429–34.

47. Biari K., Gaudioso A., Carmen Fernandez-Alonso M. et al. Peptidoglycan recognition by wheat germ agglutinin. A view by NMR. Natural Product Communications. 2019;14(5):1934578X19849240. DOI: 10.1177/1934578X19849240.

48. Bolton E.J., King J, Preketes A.P., Clingan P.R. A randomized controlled trial of an oral muramyl dipeptide (GMDP) for the reduction of leukopenia and thrombocytopenia in patients receiving cytotoxic chemotherapy. Surgical Research Communications. 1998;19(2):117–28.

49. Klimova S.V., Pinegin B.V., Totolyan N.A. Antibodies to the component of the bacterial cell wall, glucosaminylmuramyl dipeptide (GMDP) in neurological patients. [Antitela k komponentu kletochnoj stenki bakterij glyukozaminilmuramil dipeptidu (GMDP) u nevrologicheskih bol'nyh]. Medicinskaya immunologiya. 1999;1(3–4):65–6. (In Russ.).

50. Sitdikova T.S., Prosekova E.V., Turyanskaya A.I. The effectiveness of immunotropic therapy in children with virus-induced bronchial asthma: the dynamics of parameters of congenital and adaptive immune response. [Effektivnost' immunotropnoj terapii u detej s virus-inducirovannoj bronhial'noj astmoj: dinamika pokazatelej vrozhdennogo i adaptivnogo immunnogo otveta]. IV Mezhdunarodnaya nauchno-prakticheskaya konferenciya «Nauchnye issledovaniya: teoriya, metodika i praktika»: tezisy dokladov. Cheboksary, 2018. 33–6. (In Russ.).

51. Alibaeva G.F., Morugova T.V., Chakryan S.A., Nasyrtdinova A.D. Evaluation of immunity parameters using glucosaminylmuramyl dipeptide in patients with urinary tract infection and diabetes mellitus type 2. [Ocenka pokazatelej immuniteta pri ispol'zovaniya glyukozaminilmuramildipeptida u bol'nyh infekciej mochevyh putej na fone saharnogo diabeta 2 tipa]. VIII (XXV) Vserossijskij diabetologicheskij kongress s mezhdunarodnym uchastiem «Saharnyj diabet – pandemiya XXI veka»: tezisy dokladov. Moskva, 2018. 198–9. (In Russ.). Available at: https://rae-org.ru/sites/default/files/all/Events/8-VDK/VDK8_tezis.pdf. [Accessed: 12.03.2019].

52. Zabkov O.I., Zurochka V.A., Dobrynina M.A. et al. Clinical diagnostic criteria of efficiency of complex etiopathogenetic therapy of chronic Epstein-Barr viral infection. [Kliniko-diagnosticheskie kriterii effektivnosti kompleksnoj etiopatogeneticheskoj terapii hronicheskoj Epshtejna-Barr virusnoj infekcii]. BONC UrO RAN. 2018;(3):1–13. (In Russ.).

53. Masalova O., Lesnova E., Onishchuk A. et al. Polyprenyl phosphates induce a high humoral and cellular response to immunization with recombinant proteins of the replicative complex of the hepatitis C virus. [Poliprenilfosfaty induciruyut vysokij gumoral'nyj i kletochnyj otvet na immunizaciyu rekombinantnymi belkami replikativnogo kompleksa virusa gepatita C]. Doklady AN. 2018;482(4):459–62. (In Russ.). DOI: 10.31857/S086956520003094-6.

54. Nesterova I.V., Nguen T.Z., Khalturina E.O. et al. The modulatory effects of glucosaminylmuramyldipeptide on the transformed phenotype of the subset of IFNα/βR1+IFNγR+TLR4 + neutrophilic granulocytes of patients with chronic herpes-viral infections in the experiment in vitro. [Moduliruyushchie effekty glyukozaminilmuramildipeptida na transformirovannyj fenotip subpopulyacii IFNα/βR1+IFNγR+TLR4+ nejtrofil'nyh granulocitov pacientov s hronicheskimi gerpes-virusnymi infekciyami v eksperimente in vitro]. Rossijskij immunologicheskij zhurnal. 2018;12(3):379–84. (In Russ.).

55. Ivanova O.N., Argunova E.F., Dmitrieva T.G. et al. The study of immunity in children with multiple papillomas. [Izuchenie osobennostej immuniteta u detej s mnozhestvennymi papillomami]. Yakutskij medicinskij zhurnal. 2018;(3):107–9. (In Russ.).

56. Khrustaleva E.V., Legostaeva O.P., Melnikova A.Yu., Zyablitskaya N.K. Modern approach to the treatment of respiratory papillomatosis. [Sovremennyj podhod k lecheniyu respiratornogo papillomatoza]. V sbornike: Materialy Mezhregional'noj nauchno-prakticheskoj konferencii otorinolaringologov Sibiri i Dal'nego Vostoka s mezhdunarodnym uchastiem «Aktual'nye voprosy otorinolaringologii». Pod obshchej red. A.A. Blockogo. Blagoveshchensk, 2018. 102–3. (In Russ.).

57. Katelnitskaya N.I., Tkacheva O.I., Domashenko E.A. et al. A comprehensive approach to the treatment of patients with human papillomavirus infection with MCO-25 surgical laser. [Kompleksnyj podhod k lecheniyu bol'nyh s papillomavirusnoj infekciej s primeneniem MSO-25 hirurgicheskogo lazera]. Venerolog. 2005;(11):11–2. (In Russ.).

58. Kubanov A.A. Modern approaches to the treatment of human papillomavirus infection of skin and mucous membranes. [Sovremennye podhody k lecheniyu papillomavirusnoj infekcii kozhi i slizistyh obolochek]. Vestnik dermatologii i venerologii. 2005;(4):8–12. (In Russ.).

59. Rogovskaya S.I., Mezhevitinova E.A., Prilepskaya V.N. Genital condylomas caused by human papillomavirus infection. [Kondilomy genitalij, obuslovlennye papillomavirusnoj infekciej]. RMZh. 1998;6(5):6–7. (In Russ.).

60. Pinegin B.V., Minkina G.N., Agikova L.A. et al. New immunomodulator GMDP in the treatment of HPV infection of the uterine cervix. [Ispol'zovanie novogo immunomodulyatora GMDP pri lechenii bol'nyh papillomavirusnoj infekciej shejki matki]. Immunologiya. 1997;(1):49–51. (In Russ.).

61. Randomized, open two-period cross-sectional study of comparative pharmacokinetics and bioequivalence of Licopid tablets, dispersed 0.5 mg (Peptek JSC, Russia) and Licopid® tablets, 1 mg (Peptek JSC, Russia) in healthy volunteers after a single ingestion on an empty stomach. RCT No. 297 (06.25.2018). [Randomizirovannoe, otkrytoe dvuhperiodnoe perekrestnoe issledovanie sravnitel'noj farmakokinetiki i bioekvivalentnosti preparata Likopid tabletki, dispergiruemye 0,5 mg (AO «Peptek», Rossiya) i preparata Likopid® tabletki, 1 mg (AO «Peptek», Rossiya) u zdorovyh dobrovol'cev posle odnokratnogo priema vnutr' natoshchak. RKI №297 (25.06.2018)]. (In Russ.). Available at: http://grls.rosminzdrav.ru/CIPermissionMini. aspx?CIStatementGUID=b4a26bb4-30f8-4d7c-940c4c551292615c&CIPermGUID=9033AC37-AFCE-4EFE-A277- A5E7FBAC13CB. [Accessed: 24.02.2019].

62. A prospective, single-site, open-label clinical study of the tolerability, safety and pharmacokinetics of GMDP-A (glucosaminylmuramyl dipeptide acid), solution for subcutaneous administration of 20 mg/2 ml (Peptek JSC, Russia) in healthy volunteers. RCT No. 152 (04.02.2018). [Prospektivnoe odnocentrovoe otkrytoe klinicheskoe issledovanie perenosimosti, bezopasnosti i farmakokinetiki preparata GMDP-A (glyukozaminilmuramildipeptid kislota), rastvor dlya podkozhnogo vvedeniya 20 mg/2 ml (AO «Peptek», Rossiya) u zdorovyh dobrovol'cev. RKI №152 (02.04.2018)]. (In Russ.). Available at: http://grls.rosminzdrav.ru/ CIPermissionMini.aspx?CIStatementGUID=2064a38c-8828- 4048-95d2-d75d91f5c446&CIPermGUID=3049C74B-11A0- 4282-9CA5-29566A451860. [Accessed: 24.02.2019].

63. An open clinical study for assessment of safety and tolerability, pharmacokinetics of «Licopid Fast®, a lyophilisate for solution for injection, 0.125 mg» (Peptek JSC, Russia) in healthy volunteers at intramuscular administration. RCT No. 143 (03.28.2018). [Otkrytoe klinicheskoe issledovanie po ocenke bezopasnosti i perenosimosti, farmakokinetiki preparata «Likopid Fast®, liofilizat dlya prigotovleniya rastvora dlya in"ekcij, 0,125 mg» (AO «Peptek», Rossiya) u zdorovyh dobrovol'cev pri vnutrimyshechnom vvedenii. RKI №143 (28.03.2018). (In Russ.). Available at: http://grls.rosminzdrav.ru/CIPermissionMini. aspx?CIStatementGUID=cabe5465-891a-4ad8-a3a9- 27c8ef393619&CIPermGUID=E96BE1CA-D873-4060-A077- EBD67F8B9373. [Accessed: 24.02.2019].

64. Dolgushina V.F., Telesheva L.F., Ahmatova A.N. et al. Clinicoimmunological substantiation immunotropic therapy of chronic cervicitis associated with HPV infection. [Kliniko-immunologicheskoe obosnovanie immunotropnoj terapii hronicheskogo cervicita, associirovannogo s papillomavirusnoj infekciej]. Ural'skij medicinskij zhurnal. 2009;3(57):58–62. (In Russ.).

65. Kolesnikova N.V. Clinical and immunological efficacy of murmyldipeptide (GMDP) in fertility disorders (scientific review). [Kliniko-immunologicheskaya effektivnost' murmildipeptidov (GMDP) pri narusheniyah reproduktivnoj funkcii]. Kubanskij nauchnyj medicinskij vestnik. 2017;24(5):120–8. DOI: 10.25207/1608-6228-2017-24-5-120-128. (In Russ.).

66. Manukhin I.B., Minkina G.M., Vysotskiy M.M., Kharlova O.G. Complex treatment of patients with local and diffuse condylomatosis of the uterine cervix. [Kompleksnoe lechenie pacientok s lokal'nym i rasprostranennym kondilomatozom shejki matki]. Voprosy ginekologii, akusherstva i perinatologii. 2005;4(1):20–4. (In Russ.).

67. Mynbaev O.A., Eliseeva M.Yu., Manukhin I.B. et al. Immunomodulators’ application in gynecology: myths and reality. [Primenenie immunomodulyatorov v ginekologii: mify i real'nost']. Effektivnaya farmakoterapiya v akusherstve i ginekologii. 2010;5(5):10–3. (In Russ.).

68. Pinegin B.V., Minkina G.N., Manukhin I.B. et al. The effect of glucosaminylmuramyl dipeptide on the immune and clinical status in patients with cervical lesions by human papillomavirus. [Vliyanie glyukozaminilmuramildipeptida na immunnyj status i klinicheskoe sostoyanie bol'nyh s porazheniem shejki matki virusom papillomy cheloveka]. Immunologiya. 1994;(3):46–9. (In Russ.).

69. Rakhmatullina M.R., Nechaeva I.A. Immunotropic therapy with Licopid for children suffering from papilloma viral infection. [Immunotropnaya terapiya detej s papillomavirusnoj infekciej preparatom Likopid]. Vestnik dermatologii i venerologii. 2009;(6):109–12. (In Russ.).

70. Stolyarova, U.V., Khvorostukhina, N.F., Mikheeva, Yu.V. Complex treatment of cervical papillomavirus infection. [Kompleksnoe lechenie papillomavirusnoj infekcii shejki matki]. Izvestiya Samarskogo nauchnogo centra RAN. 2014;16(5–4):1456–8. (In Russ.).

71. Khryanin A.A. Our response is resistance. Immunomodulating therapy of sexually transmitted infections from the standpoint of evidence-based medicine. [Nash otvet rezistentnosti. Immunomoduliruyushchaya terapiya infekcij, peredavaemyh polovym putyom, s pozicij dokazatel'noj mediciny]. StatusPraesens. Ginekologiya, akusherstvo, besplodnyj brak. 2016;32(3):46–55. (In Russ.).

72. Omelyanovsky V.V., Fedyaeva V.K., Musina N.Z. The concept of multi-criteria analysis of decision-making in the current system of health technology assessment in Russia. [Koncepciya mnogokriterial'nogo analiza prinyatiya reshenij v tekushchej sisteme ocenki tekhnologij v zdravoohranenii Rossii]. FARMAKOEKONOMIKA. Sovremennaya farmakoekonomika i farmakoepidemiologiya. 2018;11(3):3–7. (In Russ.). DOI: 10.17749/2070-4909.2018.11.3-003-007.

73. Vatolin V.M., Sukhorukikh O.A., Galeeva Zh.A. et al. Methods of clinical assessment from the “Clinical Recommendations” resource of the Ministry of Healthcare of Russia: a systematic review. [Analiz dannyh o metodikah klinicheskoj ocenki, ukazannyh v klinicheskih rekomendaciyah, razmeshchennyh na informacionnom resurse Minzdrava Rossii «Rubrikator klinicheskih rekomendacij». FARMAKOEKONOMIKA. Sovremennaya farmakoekonomika i farmakoepidemiologiya. 2018;11(1):56–63. (In Russ.). DOI: 10.17749/2070-4909.2018.11.1.056-063.

74. Zhuravleva N.I., Shubina LS, Sukhorukikh O.A. The use of the level of evidence and grade of recommendations scales in developing clinical guidelines in the Russian Federation. [Obzor metodik ocenki dostovernosti nauchnyh dokazatel'stv i ubeditel'nosti rekomendacij, primenyaemyh pri razrabotke klinicheskih rekomendacij v Rossijskoj Federacii]. FARMAKOEKONOMIKA. Sovremennaya farmakoekonomika i farmakoepidemiologiya. 2019;12(1):34–41. (In Russ.). DOI: 10.17749/2070-4909.2019.12.1.34-41.

75. Kolesnikova N.V., Kozlov I.G., Guryanova S.V. et al. Clinical and immunological efficiency of muramyl dipeptides in the treatment of atopic diseases. [Kliniko-immunologicheskaya effektivnost' i perspektivy ispol'zovaniya muramildipeptidov v lechenii atopicheskih zabolevanij]. Medicinskaya immunologiya. 2016;18(1):15–20. (In Russ.).

76. Kolesnikova N.V., Andronova T.M. Immunotropic effects of glucosaminylmuramyldipeptide in herpes infection in children. [Immunotropnye effekty glyukozaminilmuramildipeptida pri gerpeticheskom infekcii u detej]. Voprosy prakticheskoj pediatrii. 2016;11(5):56–61. (In Russ.).

77. Zhukova OV, Kononova S.V. Method «cost-effectiveness» in evaluation of atibiotic treatment of acytr obstructive bronchitis in children in hospital. [Metod «zatraty-effektivnost'» v ocenke antibiotikoterapii ostrogo obstruktivnogo bronhita u detej v usloviyah stacionara]. FARMAKOEKONOMIKA. Sovremennaya farmakoekonomika i farmakoepidemiologiya. 2016;9(3):30–7. (In Russ.). DOI: 10.17749/2070-4909.2016.9.3.030-037.

78. Musina N.Z, Tarasov V.V. Prospects for the use of methods of economic evaluation at the stage

79. of planning and organization of clinical studies. [Perspektivy primeneniya metodov kliniko-ekonomicheskogo analiza na etape planirovaniya i organizacii klinicheskih issledovanij]. FARMAKOEKONOMIKA. Sovremennaya farmakoekonomika i farmakoepidemiologiya. 2016;9(1):79–83. (In Russ.). DOI: 10.17749/2070-4909.2016.9.1.079-083.

80. Gomon Yu.M., Arepyeva MA, Balykina Yu.E. et al. Modeling microbial drug-resistance: from mathematics to pharmacoeconomics. [Prognozirovanie rezistentnosti: ot matematicheskogo modelirovaniya k farmakoekonomike]. FARMAKOEKONOMIKA. Sovremennaya farmakoekonomika i farmakoepidemiologiya. 2018;11(1):27–36. (In Russ.). DOI: 10.17749/2070-4909.2018.11.1.027-036.

81. Teptsova T.S., Bezdenezhnykh T.P., Fedyaeva V.K. et al. Determination of a willingness-to-pay threshold and decisionmaking in financing the healthcare technologies. [Vozmozhnye metodiki opredeleniya poroga gotovnosti platit' dlya prinyatiya reshenij o finansirovanii tekhnologij zdravoohraneniya za schet byudzhetnyh sredstv]. FARMAKOEKONOMIKA. Sovremennaya farmakoekonomika i farmakoepidemiologiya. 2018;11(3):13–22. (In Russ.). DOI: 10.17749/2070-4909.2018.11.3-013-022.


For citation:


Makatsariya A.D., Bitsadze V.O., Khizroeva J.K., Vikulov G.K., Gomberg M.A., Khryanin A.A. Efficacy and safety of glucosaminylmuramyl dipeptide in treatment of human papillomavirus-associated diseases: a systematic review. Obstetrics, Gynecology and Reproduction. 2019;13(2):132-154. https://doi.org/10.17749/2313-7347.2019.13.2.132-154

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ISSN 2313-7347 (Print)
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