HDV-RNA and HBsAg Evolution during peg-IFN Treatment in Three HBV-HDV-HCV-HIV Coinfected Patients


Background: Patients coinfected with HBV, HDV, HCV and HIV are usually excluded from clinical trials. Data on pegylated interferon treatment in this setting are limited, with predictive factors for HDV virologic success being unknown. Objectives: In this study we analyzed the time course of HDV viral load and HBsAg in HBV-HDV-HCV-HIV patients, who underwent pegylated alfa-2a interferon (peg-IFN) therapy for HDV infection between 2005 and 2009, with different virologic outcomes (no response, relapse or sustained response). Methods: Three patients were selected for virologic analysis, since complete clinical and laboratory data and stored residual blood samples, collected before/during/after peg-IFN treatment were available. Plasma samples were retrospectively analyzed for HDV-RNA detection and quantitative HBsAg determination. Results: All patients were HCV-Ab positive, persistently HCV-RNA negative, and received a peg-IFN treatment curse (180 mcg/week) for 12 to 18 months. HIV and HBV viral loads remained undetectable due to underlying Tenofovir/Emtricitabine (TDF/FTC) treatment. Low baseline HDV-RNA and HBsAg levels were both observed in the patient with sustained viral response. A HDV-RNA decline greater than 2log10 at month 6 was observed in two of the three patients, both with compensated liver cirrhosis, achieving a viral clearance at the end of treatment. Conclusions: Although performed in few patients, this study suggests that a decline of HDV-RNA during treatment and low baseline quantitative HBsAg may be associated to HDV virologic response to peg-IFN in HIV-infected subjects, independently of fibrosis stage. If confirmed on larger patient number, these data may help to select those HDV-infected patients with a reliable chance to respond to prolonged peg-IFN treatment and suggest the importance of quantitative HBsAg monitoring in this setting.

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A. Rosa Garbuglia, D. Lapa, A. Testa, M. Rosaria Capobianchi and U. Visco-Comandini, "HDV-RNA and HBsAg Evolution during peg-IFN Treatment in Three HBV-HDV-HCV-HIV Coinfected Patients," World Journal of AIDS, Vol. 2 No. 4, 2012, pp. 294-299. doi: 10.4236/wja.2012.24039.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] C. Castellares, P. Barreiro, L. Martín-Carbonero, P. Labarga, M. E. Vispo, R. Casado, L. Galindo, P. García-Gascó, J. García-Samaniego and V. Soriano, “Liver Cirrhosis in HIV-Infected Patients: Prevalence, Aetiology and Clinical Outcome,” Journal of Viral Hepatitis, Vol. 15, No. 3, 2008, pp. 165-172.
[2] V. Soriano, E. Vispo, P. Labarga, J. Medrano and P. Barreiro, “Viral Hepatitis and HIV Co-Infection,” Antiviral Research, Vol. 85, No. 1, 2010, pp. 303-315. doi:10.1016/j.antiviral.2009.10.021
[3] G. A. Niro, A. Ciancio, G. B. Gaeta, A. Smedile, A. Marrone, A. Olivero, M. Stanzione, E. David, G. Brancaccio, R. Fontana, F. Perri, A. Andriulli and M. Rizzetto, “pegylated Interferon Alpha-2b as Monotherapy or in Combination with Ribavirin in Chronic Hepatitis Delta,” Hepatology, Vol. 44, No. 3, 2006, pp. 713-720. doi:10.1002/hep.21296
[4] I. Rosa, L. Costes, V. Garrait and M. Chousterman, “Efficacy of pegylated Interferon Alpha-2b for the Treatment of Chronic Delta Hepatitis in a Patient Co-Infected with HIV,” AIDS, Vol. 19, No. 18, 2005, pp. 2177-2178. doi:10.1097/01.aids.0000194794.13305.08
[5] F. Le Gal, E. Gordien, D. Affolabi, T. Hanslik, C. Alloui, P. Dény and E. Gault, “Quantification of Hepatitis Delta Virus RNA in Serum by Consensus Real-Time PCR Indicates Different Patterns of Virological Response to Interferon Therapy in Chronically Infected Patients,” Journal Clinical Microbiology, Vol. 43, No. 5, 2005, pp. 2363-2369. doi:10.1128/JCM.43.5.2363-2369.2005
[6] C. Castelnau, F. Le Gal, M. P. Ripault, E. Gordien, M. Martinot-Peignoux, N. Boyer, B. N. Pham, S. Maylin, P. Bedossa, P. Dény, P. Marcellin and E. Gault, “Efficacy of peginterferon Alpha-2b in Chronic Hepatitis Delta: Relevance of Quantitative RT-PCR for Follow-Up,” Hepatology, Vol. 44, No. 3, 2006, pp. 536-539. doi:10.1002/hep.21325
[7] E. K. Manesis, M. Schina, F. Le Gal, O. Angelopoulou, C. Papaioannou, C. Kalligeros, V. Arseniou, S. Manolakopoulos, E. S. Hadziyannis, E. Gault, J. Koskinas, G. Papatheodoridis and A. J. Archimandritis, “Quantitative Analysis of Hepatitis D Virus RNA and Hepatitis B Surface Antigen Serum Levels in Chronic Delta Hepatitis Improves Treatment Monitoring,” Antiviral Therapy, Vol. 12, No. 3, 2007, pp. 381-388.
[8] A. Theamboonlers, T. Hansurabhanon, V. Verachai, V. Chongsrisawat and Y. Poovorawan, “Hepatitis D Virus Infection in Thailand: HDV Genotyping by RT-PCR, RFLP and Direct Sequencing,” Infection, Vol. 30, No. 3, 2002, pp. 140-144. doi:10.1007/s15010-002-2061-x
[9] M. Buti, M. Homs, F. Rodriguez-Frias, G. Funalleras, R. Jardì, S. Sauleda, D. Tabernero, M. Schaper and R. Esteban, “Clinical Outcome of Acute and Chronic Hepatitis Delta over Time: A Long-Term Follow-Up Study,” Journal of Viral Hepatitis, Vol. 18, No. 6, 2011, pp. 434-442. doi:10.1111/j.1365-2893.2010.01324.x
[10] E. Polilli, F. Sozio, E. Mazzotta, A. Pieri, L. Alterio, E. Placido, A. Agostinone , F. Di Masi , M. Tontodonati, A. Consorte, L. Cosentino and G. Parruti, “Fatal Reactivation of HBV and HDV during a Long-Lasting Interruption of HAART in a Patient Co-Infected with HIV, HCV, HBV and HDV,” Infez Med, Vol. 18, No. 1, 2010, pp. 43-47.
[11] J. Gozlan, K. Lacombe, E. Gault, G. Raguin and P. M. Girard, “Complete Cure of HBV-HDV Co-Infection after 24 Weeks of Combination Therapy with pegylated Interferon and Ribavirin in a Patient Co-Infected with HBV/HCV/HDV/HIV,” Journal of Hepatology, Vol. 50, No. 2, 2009, pp. 432-434. doi:10.1016/j.jhep.2008.05.029
[12] E. Sagnelli, N. Coppola, C. Scolastico, P. Filippini, T. Santantonio, T. Stroffolini and F. Piccinino, “Virologic and Clinical Expressions of Reciprocal Inhibitory Effect of Hepatitis B, C, and Delta Viruses in Patients with Chronic Hepatitis,” Hepatology, Vol. 32, No. 5, 2000, pp. 1106-1110. doi:10.1053/jhep.2000.19288
[13] H. Wedemeyer and M. P. Manns, “Epidemiology, Pathogenesis and Management of Hepatitis D: Update and Challenges Ahead (Review),” Nature Reviews Gastroenterology & Hepatology, Vol. 7, No. 1, 2010, pp. 31-40.
[14] Y. Benhamou, M. Bochet, V. Di Martino, F. Charlotte, F. Azria, A. Coutellier, M. Vidaud, F. Bricaire, P. Opolon, C. Katlama and T. Poynard, “Liver Fibrosis Progression in Human Immunodeficiency Virus and Hepatitis C Virus Coinfected Patients. The Multivirc Group,” Hepatology, Vol. 30, No. 4, 1999, pp. 1054-1058. doi:10.1002/hep.510300409
[15] M. Núnez, B. Ramos, B. Díaz-Pollán, N. Camino, L. Martìn-Carbonero, P. Barreiro, J. González-Lahoz and V. Soriano, “Virological Outcome of Chronic Hepatitis B Virus Infection in HIV-Coinfected Patients Receiving Anti-HBV Active Antiretroviral Therapy,” AIDS Research and Human Retroviruses, Vol. 22, No. 9, 2006, pp. 842-848. doi:10.1089/aid.2006.22.842
[16] P. Tuma, J. Medrano, S. Resino, E. Vispo, A. Madejòn, C. Sanchez-Piedra, P. Rivas, P. Labarga, L. Martín-Carbonero, P. Barreiro and V. Soriano, “Incidence of Liver Cirrhosis in HIV-Infected Patients with Chronic Hepatitis B or C in the Era of Highly Active Antiretroviral Therapy,” Antiviral Therapy, Vol. 15, No. 6, 2010, pp. 881-886. doi:10.3851/IMP1630
[17] K. Zachou, C. Yurdaydin, U. Drebber, G. N. Dalekos, A. Erhardt, Y. Cakaloglu, H. Degertekin, S. Gurel, S. Zeuzem, H. Bozkaya, V. Schlaphoff, H. P. Dienes, T. C. Bock, M. P. Manns and H. Wedemeyer, “HIDT-1 Study Group. Quantitative HBsAg and HDV-RNA Levels in Chronic Delta Hepatitis,” Liver International, Vol. 30, No. 3, 2010, pp. 430-437. doi:10.1111/j.1478-3231.2009.02140.x
[18] J. Sheldon, B. Ramos, C. Toro, P. Rìos, J. Martinez- Alarcòn, M. Bottecchia, M. Romero, J. Garcia-Samaniego and V. Soriano, “Does Treatment of Hepatitis B Virus (HBV) Infection Reduce Hepatitis Delta Virus (HDV) Replication in HIV-HBV-HDV-Coinfected Patients?” Antiviral Therapy, Vol. 13, No. 1, 2008, pp. 97-102.
[19] J. Millum and J. Menikoff, “Streamlining Ethical Re- view,” Annal International Medecine, Vol. 153, No. 10, 2010, pp. 655-657.

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