Despite a rising incidence of acute HCV in patients infected with HIV, the optimal therapeutic strategy (pegylated interferon-α [PEG-IFN-α] monotherapy or in combination with ribavirin) is still under debate.
Methods
A total of 23 HIV-infected patients were prospectively diagnosed with acute HCV and treated with PEG-IFN-α2a monotherapy (180 μg/week) for 24 or 48 weeks. Add-on ribavirin was allowed from week 4 of therapy onwards. There were three patients who were not included for different reasons. Blood samples were routinely drawn for viral load measurement and IL28B polymorphism analysis.
Results
Spontaneous viral clearance occurred in 1 (4%) patient. Nineteen patients (13 genotype 1 and 6 genotype 4) received treatment with PEG-IFN-α monotherapy (3 with add-on ribavirin) resulting in a rapid virological response (HCV RNA<50 IU/ml at week 4) in 7 (37%) patients. A sustained virological response (SVR) was reached in 7 (37%) patients, whereas 9 (47%) patients were null-responders to treatment (that is, <2 log10 drop in HCV RNA at week 12 of therapy). The unfavourable G allele of the IL28B polymorphism rs8099917 was detected in 66% of the non-responders. In case of re-emergence of HCV viraemia after treatment discontinuation, sequence analysis of quasispecies confirmed an HCV relapse in 3 patients while 2 patients were re-infected by their previously non-responding partner.
Conclusions
PEG-IFN-α monotherapy resulted in a low SVR rate and a high percentage of null-response, whereas non-SVR was associated with a polymorphism in the IL28B gene (rs8099917).
References
1.
DantaM., BrownD., BhaganiS.Recent epidemic of acute hepatitis C virus in HIV-positive men who have sex with men linked to high-risk sexual behaviours. AIDS2007; 21: 983–991.
2.
MatthewsG.V., HellardM., KaldorJ., LloydA., DoreG.J.Further evidence of HCV sexual transmission among HIV-positive men who have sex with men: response to Danta, et al. AIDS2007; 21: 2112–2113.
3.
UrbanusA.T., van de LaarT.J., StolteI.G.Hepatitis C virus infections among HIV-infected men who have sex with men: an expanding epidemic. AIDS2009; 23: F1–F7.
4.
van de LaarT.J., van der BijA.K., PrinsM.Increase in HCV incidence among men who have sex with men in Amsterdam most likely caused by sexual transmission. J Infect Dis2007; 196: 230–238.
5.
RockstrohJ.K., BhaganiS., BenhamouY.European AIDS Clinical Society (EACS) guidelines for the clinical management and treatment of chronic hepatitis B and C coinfection in HIV-infected adults. HIV Med2008; 9: 82–88.
6.
SorianoV., PuotiM., SulkowskiM.Care of patients coinfected with HIV and hepatitis C virus: 2007 updated recommendations from the HCV-HIV International Panel. AIDS2007; 21: 1073–1089.
7.
CalleriG., CaritiG., GaiottinoF.A short course of pegylated interferon-alpha in acute HCV hepatitis. J Viral Hepat2007; 14: 116–121.
8.
JaeckelE., CornbergM., WedemeyerH.Treatment of acute hepatitis C with interferon alfa-2b. N Engl J Med2001; 345: 1452–1457.
9.
WiegandJ., BuggischP., BoecherW.Early monotherapy with pegylated interferon alpha-2b for acute hepatitis C infection: the HEP-NET acute-HCV-II study. Hepatology2006; 43: 250–256.
10.
ArendsJ.E., SchroverI.M., SchaarC.G., MudrikovaT., HoepelmanA.I.Peginterferon monotherapy for the treatment of acute hepatitis C in HIV-coinfected patients. AIDS2008; 22: 1381–1382.
11.
VogelM., RockstrohJ.K.Treatment of acute hepatitis C in HIV infection. J Antimicrob Chemother2010; 65: 4–9.
12.
DominguezS., GhosnJ., ValantinM.A.Efficacy of early treatment of acute hepatitis C infection with pegylated interferon and ribavirin in HIV-infected patients. AIDS2006; 20: 1157–1161.
13.
FiererD.S., FishmanS., UrielA.J.Characterization of an Outbreak of Acute HCV Infection in HIV-infected Men in New York City.16th Conference on Retroviruses and Opportunistic Infections. 8–11 February 2009, Montreal, QC, Canada. Abstract 802.
14.
GilleeceY.C., BrowneR.E., AsboeD.Transmission of hepatitis C virus among HIV-positive homosexual men and response to a 24-week course of pegylated interferon and ribavirin. J Acquir Immune Defic Syndr2005; 40: 41–46.
15.
LambersF., van den BerkG., van der MeerJ.Treatment Outcome of Acute Hepatitis C Virus Infection in HIV-infected MSM: The Effect of Treatment Length.17th Conference on Retroviruses and Opportunistic Infections. 16–19 February 2010, San Francisco, CA, USA. Abstract 641.
16.
LuetkemeyerA., HareC.B., StansellJ.Clinical presentation and course of acute hepatitis C infection in HIV-infected patients. J Acquir Immune Defic Syndr2006; 41: 31–36.
17.
MatthewsG.V., HellardM., HaberP.Characteristics and treatment outcomes among HIV-infected individuals in the Australian Trial in Acute Hepatitis C. Clin Infect Dis2009; 48: 650–658.
18.
SchnurigerA., DominguezS., GuiguetM.Acute hepatitis C in HIV-infected patients: rare spontaneous clearance correlates with weak memory CD4 T-cell responses to hepatitis C virus. AIDS2009; 23: 2079–2089.
19.
DantaM., TurnerJ.M., JohnstoneR.Use of pegylated interferon-alpha (peg-IFN) with or without ribavirin in the treatment of acute HCV in HIV-positive individuals. HIV Med2005; 6: 14–55.
20.
De RosaF.G., MollarettiO., AudagnottoS.Efficacy of early pegylated interferon alpha-2b monotherapy for acute hepatitis C in HIV-infected patients. Clin Infect Dis2009; 48: 1636–1637.
21.
Schulze zur WieschJ., PieperD., StahmerI.Sustained virological response after early antiviral treatment of acute hepatitis C virus and HIV coinfection. Clin Infect Dis2009; 49: 466–472.
22.
SerpaggiJ., ChaixM.L., BatisseD.Sexually transmitted acute infection with a clustered genotype 4 hepatitis C virus in HIV-1-infected men and inefficacy of early antiviral therapy. AIDS2006; 20: 233–240.
23.
VogelM., BieniekB., JessenH.Treatment of acute hepatitis C infection in HIV-infected patients: a retrospective analysis of eleven cases. J Viral Hepat2005; 12: 207–211.
24.
VogelM., NattermannJ., BaumgartenA.Pegylated interferon-alpha for the treatment of sexually transmitted acute hepatitis C in HIV-infected individuals. Antivir Ther2006; 11: 1097–1101.
ThomasD.L., ThioC.L., MartinM.P.Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature2009; 461: 798–801.
27.
GeD., FellayJ., ThompsonA.J.Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature2009; 461: 399–401.
28.
SuppiahV., MoldovanM., AhlenstielG.IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet2009; 41: 1100–1104.
29.
RauchA., KutalikZ., DescombesP.Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study. Gastroenterology2010; 138: 1338–1345.
30.
TanakaY., NishidaN., SugiyamaM.Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet2009; 41: 1105–1109.
31.
AlbertiA., ClumeckN., CollinsS.Short statement of the first European Consensus Conference on the treatment of chronic hepatitis B and C in HIV co-infected patients. J Hepatol2005; 42: 615–624.
32.
ArendsJ.E., MudrikovaT., WensingA.M.J., WindC.M., van BaarleD., HoepelmanA.I.M.High percentage of non-response with peginterferon-alfa-2a monotherapy for the treatment of acute hepatitis C in HIV infected patients.49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). 12–15 September 2009, San Francisco, CA, USA. Abstract 2458.
33.
KatohK., AsimenosG., TohH.Multiple alignment of DNA sequences with MAFFT. Methods Mol Biol2009; 537: 39–64.
34.
AsselahT.Genetic polymorphism and response to treatment in chronic hepatitis C: the future of personalized medicine. J Hepatol2010; 52: 452–454.
35.
GerlachJ.T., DiepolderH.M., ZachovalR.Acute hepatitis C: high rate of both spontaneous and treatment-induced viral clearance. Gastroenterology2003; 125: 80–88.
36.
TaiA.W., ChungR.T.Treatment failure in hepatitis C: mechanisms of non-response. J Hepatol2009; 50: 412–420.
37.
NúñezM., MirallesC., BerdunM.A.Role of weight-based ribavirin dosing and extended duration of therapy in chronic hepatitis C in HIV-infected patients: the PRESCO trial. AIDS Res Hum Retroviruses2007; 23: 972–982.
38.
MartinP., JensenD.M.Ribavirin in the treatment of chronic hepatitis C. J Gastroenterol Hepatol2008; 23: 844–855.
39.
MorelloJ., Rodriguez-NovoaS., Jimenez-NacherI., SorianoV.Usefulness of monitoring ribavirin plasma concentrations to improve treatment response in patients with chronic hepatitis C. J Antimicrob Chemother2008; 62: 1174–1180.
40.
ThompsonA.J., FellayJ., PatelK.Variants in the ITPA gene protect against ribavirin-induced hemolytic anemia and decrease the need for ribavirin dose reduction. Gastroenterology2010; 139: 1181–1189.
41.
AsselahT., EstrabaudE., BiecheI.Hepatitis C: viral and host factors associated with non-response to pegylated interferon plus ribavirin. Liver Int2010; 30: 1259–1269.
42.
NattermannJ., VogelM., BaumgartenA.Genetic variation in IL28B and treatment-induced clearance of HCV in HCV/HIV co-infected patients.17th Conference on Retroviruses and Opportunistic Infections. 16–19 February 2010, San Francisco, CA, USA. Abstract 164.
43.
ChenL., BorozanI., FeldJ.Hepatic gene expression discriminates responders and nonresponders in treatment of chronic hepatitis C viral infection. Gastroenterology2005; 128: 1437–1444.
44.
YounossiZ.M., BaranovaA., AfendyA.Early gene expression profiles of patients with chronic hepatitis C treated with pegylated interferon-alfa and ribavirin. Hepatology2009; 49: 763–774.
