A Review on Inosine Pranobex Immunotherapy for Cervical HPV-Positive Patients

Figures & data

Table 1 Summary of Studies Investigating the Efficacy of IP Therapy in HPV Genital Infections, Especially Cervical Infections

HPV Infection	Therapeutic Scheme	IP Treatment Duration and Dose Regimes	№ of Patients	Age	Follow Up
Genital warts^Citation61	CO2 laser or CO2 laser plus IP	–	–	–	–
Main findings^Citation61 Monotherapy was less efficacious than the combination treatments.^Citation61 Combination therapy consisting of CO2 laser plus isoprinosine significantly reduced the number of recurring condyloma acuminate.^Citation61
Genital warts^Citation62	Conventional treatment Conventional treatment plus IP therapy	One gram IP three times daily by mouth for four weeks	165 patients: 85 men/80 women	21–22 years	At 6 and 8 weeks and hereafter every four weeks, up to 24 weeks.
Main findings^Citation62 Conventional therapy alone had 41% efficacy, the combination of IP plus conventional therapy increased efficacy to 94%.^Citation62
Genital warts^Citation63	Conventional treatment (podophyllin or trichloroacetic acid) plus IP	4 week course of inosine pranobex 3 g a day	55	Over 18 years	At 8 and 12 weeks from entering the study
Main findings^Citation63 The IP therapy improved the relative clinical efficacy of the conventional treatment (podophyllin or trichloroacetic acid).^Citation63
Genital warts^Citation64	Destructive methods alone and with IP combination	IP- 3 g a day	-	20–30 years	8 month
Main findings^Citation64 The combination therapy had long-term efficacy and there was only a 7% relapse rate. In contrast, destructive therapy was associated with a 32% relapse rate.^Citation64
Vulvar HPV infection^Citation65	IP therapy alone and placebo	1 g IP thrice daily for 6 weeks	55	-	2 month
Main findings.^Citation65 IP monotherapy proved effective in 14 (63.5%) of the patients. However, only 4 patients (16.7%) in the placebo group presented with substantial improvement in vulvar epithelial morphology (P = 0.005).65 The authors concluded that IP therapy is suitable for the treatment of vulvar HPV infections.^Citation65
Genital HPV infection^Citation71	IP monotherapy and combined treatments	IP dose of 50 mg/kg of body weight for 10 days as a monotherapy or in combination	5.650	Under 20 years -over 66 years	6 months
Main findings^Citation71 HPV self-clearance without treatment had occurred in 22.6% of all cases.^Citation71 The rates of HPV negative cases were 35.5%, 54.8%, and 84.2% after conventional, single IP, and combined IP treatments, respectively.^Citation71
Cervical HPV infection^Citation72	IP monotherapy	50 mg/kg per day thrice daily for 10 d, a break for 10 d, and later 2 more 10 d courses	123	20–80 years	6 months
Main findings^Citation72 IP treatment stopped CIN1 progression in 96.23 ± 2.62% of all patients.^Citation72 Cervical HPV clearance and full recovery were observed in 91.06% of all patients administered IP.^Citation72
Cervical HPV infection^Citation73	IP monotherapy	Three courses of 3000 mg IP daily at 10 d intervals between courses.	39	18–35 years	6 months
Main findings^Citation73 At the end of the trial, viral load declined to a clinically insignificant level in 17.95% of all women and there was 74.36% cervical HPV clearance.^Citation73
Cervical HPV infection and dysplasia^Citation74	Radio-wave conization and IP therapy	Three courses of 1.000 mg IP thrice daily for 10 d with 14 d intervals between courses	80	19–47 years	6 months
Main findings^Citation74 At the end of the study, clearance of cervical HPV infection was confirmed for 97.5% of all patients.^Citation74
Cervical HPV infection^Citation67	Electro-ablation plus IP therapy and IP monotherapy	1000 mg oral IP monotherapy thrice daily - 10 d	100	19–35 y.	60 days and 6 months
Main findings^Citation67 Cervical HPV PCR revealed 88% clearance of cervical HPV infection at IP monotherapy group after 6 mo.^Citation67 In the II group, the combined treatment provided 93.5% cervical HPV clearance after 6 mo.^Citation67
Cervical HPV 16, HPV 18 infection^Citation75	IP monotherapy	IP – 1g tid., 10 days	45	32.2 ± 2.7 years	6 months
Main findings^Citation75 Following a course of IP treatment: HPV 16 and 18 were undetectable in 77.8% and 50% of treated patients.^Citation75
Cervical HPV infection^Citation76	IP monotherapy (I, II groups) and no therapy (III group)	Six 0.500-mg IP tablets taken at 8-h intervalsfor 14 (II group) and 28 (I group) days	125	32.2 ± 2.7	6 months
Main findings^Citation76 After 6 mo, there was no evidence of cervical HPV infection in 93.7%, 78.0%, and 43.6% of the women in the first, second, and third groups, respectively.^Citation76
Cervical HPV infection and HSIL^Citation11	Electroconization and electroconization plus IP therapy	1 g IP thrice daily at 8-h intervals for 1 mo. For the next 5 mo, 500 mg IP thrice daily at 8-h intervals	32	16 to 55 years	24 and 48 months
Main findings^Citation11 Long-term IP therapy reduces HSIL recurrence in HPV-positive women who have undergone surgery.^Citation11 Adjuvant IP immunotherapy augmented cervical HPV infection clearance and diminished cervical dysplasia relapses in patients who were positive for cervical HPV and who underwent HSIL surgery.^Citation11

Sadoul G, Beuret TH. Treatment of cervical and vulvar condylomata by СО2 laser also with a immunostimulant. Rev Fran Gynecol Obstet. 1984;79(11):681–684.

 PubMedGoogle Scholar

Mohanty KC, Scott CS. Immunotherapy of genital warts with inosine pranobex (Imunovir): preliminary study. Sex Transmit Infect. 1986;62:352–355. doi:10.1136/sti.62.5.352

 Google Scholar

Davidson-Parker J, Dinsmore W, Khan MH, Hicks DA, Morris CA, Morris DF. Immunotherapy of genital warts with inosine pranobex and conventional treatment: double blind placebo controlled study. Genitourin Med. 1988;64(6):383–386. doi:10.1136/sti.64.6.3832465265

 PubMedGoogle Scholar

Nejmark BA, Kondrateva JS, Zologina VS, Torbik DV. Effectiveness of combined treatment of HPV infection. Urologia. 2015;(2):39–40,42.

 Google Scholar

Tay SK. Efficacy of inosine pranobex oral therapy in subclinical human papillomavirus infection of the vulva: a randomized double-blinded placebo controlled study. Int J STD AIDS. 1996;7(4):276–280. doi:10.1258/09564629619179608876359

 PubMed Web of Science ®Google Scholar

Eliseeva MY, Manukhin IB, Mynbaev OA, Zvereva NS, Mishutina AA, Tcarev VN. Antiviral effect of isoprinosine in HPV-associated diseases. Obstet Gynecol. 2012;2:107–114.

 Google Scholar

Pestrikova TY, Pushkar VA. Evaluation of comprehensive treatment of cervical pathology associated with HPV. Gynecol. 2015;17(1):50–53. doi:10.26442/2079-5831_17.4.50-53

 Google Scholar

Pestrikova TY, Panfilova YO, Yurasova EA, Kotelnikova AV. Assessment of viral load in patients with HPV-associated cervicitis during the course of complex treatment. Gynecology. 2017;19(3):45–48.

 Google Scholar

Ordiyants IM, Buyanova NV, Abdurakhmanova MB. Recurrence of HPV infection after combination therapy of uterine cervical diseases. Obstet Gynecol News Opin Train. 2018;6(3):47–52.

 Google Scholar

Budanov PV, Churganova AA, Bakhtiyarov KR, Strizhakov AN. Human papillomavirus infection: the efficacy of treatment with inosine pranobex. Gynecology. 2015;17(6):56–59. doi:10.26442/2079-5696_17.6.56-59

 Google Scholar

Kedrova AG, Podisov YI, Kuznetsov VV, Bryugzin VV, Kozachenko VP, Nikogosyan SO. Role of antiviral therapy in the complex treatment of patients with epithelial dysplasias and preinvasive cancer of the cervix uteri. Akush Ginekol. 2006;6:27–30.

 Google Scholar

Kedrova AG. Local immunosuppressive damage in the human papillomavirus persistence. RMJ. 2017;26:1971–1976.

 Google Scholar

Kovachev S. Immunotherapy in patients with local HPV infection and high-grade squamous intraepithelial lesion following uterine cervical conization. Immunopharmacol Immunotoxicol. 2020;42(4):314–318. doi:10.1080/08923973.2020.176537432429720

 PubMed Web of Science ®Google Scholar