Treatment of Hepatitis C Virus Infection in the HIV- Infected Patients by Pegylated Interferon and Ribavirin in Tehran, Iran

Ali Pashaei Zanjani; Negin Esmaeilpour; Mehrnaz Rasoolinejad; Pardis Moradnejad; Mojtaba Hedayat Yaghoobi

doi:10.5812/ajcmi.43623

Treatment of Hepatitis C Virus Infection in the HIV- Infected Patients by Pegylated Interferon and Ribavirin in Tehran, Iran

Ali Pashaei Zanjani ¹ , Negin Esmaeilpour ² , Mehrnaz Rasoolinejad ³ , Pardis Moradnejad ¹ and Mojtaba Hedayat Yaghoobi ^{4 , *}

Authors Information

¹ Specialist of Infectious Diseases, Department of Infectious Diseases, Tehran University of Medical Sciences, Tehran, IR Iran

² Associate Professor of Infectious Diseases, Department of Infectious Diseases, Tehran University of Medical Sciences, Tehran, IR Iran

³ Professor of Infectious Diseases, Department of Infectious Diseases, Iranian Research Center for HIV/AIDS, Tehran University of Medical Sciences, Tehran, IR Iran

⁴ Assistant Professor of Infectious Diseases, Department of Infectious Diseases, Alborz University of Medical Sciences, Karaj, IR Iran

Article Notes and Dates

Avicenna Journal of Clinical Microbiology and Infection: August 2017, 4 (3); e43623.Published Online: May 7, 2017

Article Type: Brief Report; Received : November 4, 2016; Revised : March 3, 2017; Accepted : April 16, 2017
DOI: http://dx.doi.org/10.5812/ajcmi.43623

To Cite : Pashaei Zanjani A, Esmaeilpour N, Rasoolinejad M, Moradnejad P, Hedayat Yaghoobi M. et al. Treatment of Hepatitis C Virus Infection in the HIV- Infected Patients by Pegylated Interferon and Ribavirin in Tehran, Iran, Avicenna J Clin Microb Infec. 2017 ;4(3):e43623. doi: 10.5812/ajcmi.43623.

Abstract

Copyright: Copyright © 2017, Avicenna Journal of Clinical Microbiology and Infection. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.

1. Background

In the past decade, the effect of ART (antiretroviral therapy) substantially reduced AIDS (Acquired Immunodeficiency Syndrome) related mortality. Therefore, HCV (hepatitis C virus) related liver disease has become a major concern for patients with HCV co-infection (1) and end-stage liver disease has remained the main cause of death in these patients (2). Eradicating hepatitis C virus in HIV (Human Immunodeficiency Virus)/HCV co-infection patients is the best method of controlling liver disease progress (3).

For over a decade, the chief treatment of the HCV infection was a combination regimen of pegylated interferon (pegIFN) and ribavirin. Fast progress in producing anti-HCV drugs led to the discovery of a new class of DDA (direct acting antiviral) agents that aimed at HCV replication cycle. The first DDA agents were the HCV protease inhibitors boceprerir and Telaprevir, subsequently a new drug of the same class (simeprevir) and a newer class (sofosbuvir, ledipasvir) approved (4). However, high cost of the over mentioned drugs has been a global barrier to their public use and they are not yet available in all parts of the world.

The present study aims at determining SVR rates in HIV/HCV co-infected patients under pegylated interferon and ribavirin treatment referring to Tehran Imam Khomeini Hospital during 2010 - 2013.

2. Methods

In this descriptive, cross-sectional study, records of all HIV/HCV co-infected patients under pegylated interferon and ribavirin treatment referring to Tehran Imam Khomeini hospital during 2010 - 2013 were gathered and the required information was extracted.

The variables are age, sex, genotype, ART history before/after treatment, liver involvement stage and grade in biopsy, viral load levels prior to treatment, 4^th (rapid virologic response (RVR)), 12th (early virologic response (EVR)), and 48th (End of treatment response (ETR)) week as well as 6 months after treatment (sustained virologic response (SVR)), and CD4 count every 3 months in addition to the incidence of opportunistic infections.

The patients received 2 pegIFN (pegIFN alfa-2a and pegIFN alfa-2b) during the study.

The data was analyzed by the SPSS 16 software and using the t-test and Chi-Square test for analyzing quantitative and qualitative variables, respectively.

3. Results

The findings of the study show that during the course of the study, 28 patients underwent pegylated interferon and ribavirin therapy for hepatitis C. The patients were all male with the mean age of 40.3 ± 8.4 years (range: 26 - 58). There were 25 (89.3%) patients with a positive drug injection history; 6 (21.4%) and 22 (78.6%) of the patients received pegINF alfa-2b and peg INF alfa-2a, respectively. Genotypes 1, 3, and 2 were observed in 17 (61%), 9 (32%), and 2 (7%) of the patients, correspondingly. None of the patients had HBV co-infection.

The mean CD4 count was 518.16 ± 298 cell/mL. Among all, 20 (71.4%) patients received ART prior to the HCV treatment.

Half of the patients had HAI (hepatic activity index) 1 stage in their liver biopsy.

Overall, 50%, 72.7%, and 83.3% of the patients attained RVR, EVR, and ETR, respectively. The general SVR level was 67.8% and it was 52.9% and 72.7% in genotypes 1, and 2, 3 correspondingly. All patients attaining RVR, reached SVR.

The frequency of CD4 count depletion to less than 200 during the treatment period is demonstrated in Table 1. Despite CD4 decline, no opportunistic infectious disease has been reported during the treatment of hepatitis C.

Table 1. Frequency of CD4 < 200 During pegINF and Ribavirin Course of Treatment

Frequency of CD4 < 200	Time of Measurement (CD4)
6 (21.4)	3th month of treatment
8 (28.5)	6th month of treatment
12 (42.8)	9th month of treatment
6 (21.4)	Treatment termination

ART was started for 1 patient (3.6%) during the treatment period. Hepatitis C treatment was discontinued for 6 (21.4%) patients, among which, 4 were null responder and 2 could not tolerate.

CD4 count for 6 months after treatment was less than 200 cell/mL in 1 (3.5%) and 200 - 350 (17.8%) cell/mL after hepatitis C treatment; ART was initiated for 5 patients after treatment of hepatitis C.

4. Discussion

Generally, SVR rates in the HIV/HCV co-infected are lower than HCV monoinfected patients. Among patients with HIV/HCV genotype 1 co-infection SVR rates have been nearly 14% to 40% (5-8). In our study, overall SVR rates by pegINF and ribavirin regimen was 67.8%, and it was 52.9% and 72.7% in genotypes 1 and 2, 3, respectively.

In the study of Apricot, SVR rates in HIV-HCV co-infected patients under pegIFN alfa-2a and ribavirin treatment was 40%, and it was 28% and 62% in genotypes 1 and 2, 3, respectively (7). In the study of Barcaui HS et al. which was conducted on 100 HIV-HCV co-infected patients under pegIFN and ribavirin regimen treatment, SVR rates were 27% (9).

In another study, SVR rates following pegINF alfa- 2a and Ribavirin treatment were 22% and 62% in genotypes 1 and 2, 3, respectively and they were correspondingly 32% and 71% following the administration of pegIFN alfa-2b and Ribavirin in genotypes 1 and 2,3 (10). One reason for higher SVR rates in our study is the possibility of a more favorable genetic trait in Iranian HCV patients responding to pegIFN and ribavirin in Iran.

Researchers have detected a polymorphism (rs129798060) close to IL28B gene that encodes interferon lambda-3, which has a strong statistical relationship with response to IFN therapy (11, 12). In our study, all patients attaining RVR reached SVR and this shows that those getting to RVR can reach SVR in a significantly higher manner.

In the present study, despite the fact that absolute CD4 counts decline to less than 200 during the treatment, none of the patients developed opportunistic infections and ART was administered for 1 case (3.6%) due to CD4 percent decline.

4.1. Conclusions

Considering high price of free interferon regimens in Iran and proper response of the patients to pegIFN and ribavirin treatment, it seems that the regimen is still an appropriate treatment for HIV/HCV co-infected patients in Iran. Further studies are required to compare the mentioned regimen to free IFN regimens in HIV/HCV co-infected patients considering SVR rates, as well as drug side effects and interactions.

Acknowledgements

Footnote

References

1. Sulkowski MS. Current management of hepatitis C virus infection in patients with HIV co-infection. J Infect Dis. 2013; 207 Suppl 1-32[DOI][PubMed]
2. Weber R, Sabin CA, Friis-Moller N, Reiss P, El-Sadr WM, Kirk O, et al. Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study. Arch Intern Med. 2006; 166(15): 1632-41[DOI][PubMed]
3. Berenguer J, Alvarez-Pellicer J, Martin PM, Lopez-Aldeguer J, Von-Wichmann MA, Quereda C, et al. Sustained virological response to interferon plus ribavirin reduces liver-related complications and mortality in patients coinfected with human immunodeficiency virus and hepatitis C virus. Hepatology. 2009; 50(2): 407-13[DOI][PubMed]
4. Recommendations for testing, managing, and treating hepatitis C. 2014;
5. Torriani FJ, Rodriguez-Torres M, Rockstroh JK, Lissen E, Gonzalez-Garcia J, Lazzarin A, et al. Peginterferon Alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med. 2004; 351(5): 438-50[DOI][PubMed]
6. Carrat F, Bani-Sadr F, Pol S, Rosenthal E, Lunel-Fabiani F, Benzekri A, et al. Pegylated interferon alfa-2b vs standard interferon alfa-2b, plus ribavirin, for chronic hepatitis C in HIV-infected patients: a randomized controlled trial. JAMA. 2004; 292(23): 2839-48[DOI][PubMed]
7. Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001; 358(9286): 958-65[PubMed]
8. Vogel M, Ahlenstiel G, Hintsche B, Fenske S, Trein A, Lutz T, et al. The influence of HAART on the efficacy and safety of pegylated interferon and ribavirin therapy for the treatment of chronic HCV infection in HIV-positive Individuals. Eur J Med Res. 2010; 15(3): 102-11[PubMed]
9. Barcaui HS, Tavares GC, May SB, Brandao-Mello CE, Amendola Pires MM, Barroso PF. Low rates of sustained virologic response with peginterferon plus ribavirin for chronic hepatitis C virus infection in HIV infected patients in Rio de Janeiro, Brazil. PLoS One. 2013; 8(7)[DOI][PubMed]
10. Laguno M, Cifuentes C, Murillas J, Veloso S, Larrousse M, Payeras A, et al. Randomized trial comparing pegylated interferon alpha-2b versus pegylated interferon alpha-2a, both plus ribavirin, to treat chronic hepatitis C in human immunodeficiency virus patients. Hepatology. 2009; 49(1): 22-31[DOI][PubMed]
11. Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009; 461(7262): 399-401[DOI][PubMed]
12. Yu ML, Huang CF, Huang JF, Chang NC, Yang JF, Lin ZY, et al. Role of interleukin-28B polymorphisms in the treatment of hepatitis C virus genotype 2 infection in Asian patients. Hepatology. 2011; 53(1): 7-13[DOI][PubMed]

Avicenna Journal of Clinical Microbiology and Infection

Published by: Kowsar

Treatment of Hepatitis C Virus Infection in the HIV- Infected Patients by Pegylated Interferon and Ribavirin in Tehran, Iran

Abstract

1. Background

2. Methods

3. Results

4. Discussion

Acknowledgements

Footnote

References

Share This Article on: