A. Stepanov, A. Kruk, N. Polovinkina, A. Vinogradova Peoples' Friendship University of Russia, Moscow The Faculty of Medicine Chair of Infectious Diseases Chair of Internal diseases Efficacy of a 24 week course of acute HCV treatment with peg-interferon α-2b and ribavirin in HIV-infected patients A. Stepanov, A. Kruk, N. Polovinkina, A. Vinogradova

A global view of HIV infection 38.6 million people [33.4‒46.0 million] living with HIV, 2005 2.4

Officially Registered HIV Cases in the Russian Federation 1 January 1987 through 30 June 2006 (based on data from the Russian Federal AIDS Centre) 250.0 200.0 150.0 Prevalence, per 100,000 Registered HIV Cases 100.0 50.0 0.0 New Registered Cases 1090 1513 4315 3971 19758 59261 87671 49923 36396 34306 35526 13492 2603 6918 10889 30647 89908 177579 227502 263898 298204 333730 347222 0,7 1,4 4,2 6,7 19,8 59,5 118,9 152,7 178,4 202,8 227,4 235,4 1 2,9 2,7 13,5 40,8 60,8 34,6 25,3 23,9 24,9 9,5 Cumulative Registered Cases Prevalence per 100000 Annual Incidence per 100000

Increase in reported HIV cases in the Russian Federation and Ukraine, 1987-2005 Reported HIV cases in the Russian Federation Reported HIV cases in Ukraine 400 000 30 000 45 000 60 000 75 000 90 000 105 000 120 000 15 000 Russian Federation 350 000 Newly reported cases 300 000 Cumulative (previous years) 250 000 200 000 Ukraine Newly reported cases 150 000 Cumulative (previous years) 100 000 50 000 1987 1989 1991 1993 1995 1997 1999 2001 2003 2005 Sources: Russian Federal AIDS Centre; Ukranian AIDS Centre and Ministry of Health of Ukraine 2.12

HIV-infection cases reported among Russian citizens by main risk factors, 2004 (Russian Federal AIDS Centre data) Born to infected mother (0.9%) Blood Transfusion (0%) Heterosexual contact (30.0%) Homosexual contact (0.8%) IDU (68.3%)

HCV and public health HCV incidence in the world: 3 % (0,1-5 %) Chronic hepatitis C can be found in 30% of all HIV-patients HCV/HIV coinfected patients show a faster progression to cirrhosis and increased liver-related mortality In the developed countries, HCV is responsible for: 20 % of acute hepatites 70 % of chronic hepatites 40 % of decompensated cirrhosis 60 % of CHC cases 30 % of liver transplantations EASL International Consensus Conference on Hepatitis C. Paris, 26-28 February 1999. Consensus statement. J Hepatol 1999 ; 30 : 956-61. First European Consensus Conference on the treatment of chronic hepatitis B and C in HIV-coinfected patients. J Hepatol 2005; 42:615-624

Liver Disease Has Become a Major Cause of Death in the Era of Potent Antiretroviral Therapy Mortality from end-stage liver disease (ESLD) as a % of all mortalities among HIV patients 60 50% 50 45% 40 35% Mortality (%) 30 20 13% 12% 10 5% Italy (Brescia) Spain (Madrid) USA (Boston) Bica Clin Infect Dis 2001; Puoti JAIDS 2000; Soriano Eur J Epidemiol 1999; Soriano PRN Notebook 2002; Martin-Carbonero AIDS Res Human Retrovirus 2001 Pre-therapy era Therapy era

Mortality Among HIV-Infected Patients in France (GERMIVIC Study Group) Rosenthal E et al. For the GERMIVIC Joint Study Group, 2nd IAS Conference on HIV Pathogenesis and Treatment, Paris 2003; 87

Progression to HCC in HCV/HIV-Coinfected Patients HCV/HIV-coinfected patients progress more rapidly to HCC than HCV-monoinfected patients Coinfected pts also younger at HCC diagnosis, have higher AFP levels, receive HCC treatment more often HIV/HCV (n = 41) HCV (n = 119) P Value Mean duration of HCV infection at time of HCC diagnosis, yrs 26.4 (n = 30) 35.2 (n = 62) < .001 Mean age, yrs 52.4 61.1 Median AFP level, ng/mL 1274 192 .002 Excessive alcohol use, % 48.7 (n = 39) 71.0 (n = 100) .005 Receive HCC therapy, % 56 36 .025 Retrospective analysis of all HCC cases in HIV/HCV coinfected patients from 1992-2004 in 15 US and Canadian centers Comparison with all HCV-monoinfected HCC patients diagnosed in 3 tertiary care facilities from 1992-2004 Bräu N, et al. IAS 2005. Abstract TuPe1.1C17.

Study Objectives To assess the efficacy and tolerability of acute hepatitis C treatment with peg-interferon α-2b and ribavirin in the HCV/HIV co-infected population: the proportion of patients with SVR; the proportion of patients with undetectable HCV VL at the end of treatment (EOT); changes in liver enzymes from baseline to week 48.

Study Design Patients with confirmed HCV seroconversion during a period shorter than 6 months Observation period: Follow-up for 12 weeks with monthly clinical examinations HCV Treatment with PegInterferon α-2b (1.5 mcg/kg/weekly) and Ribavirin (800 mg/daily) for 24 weeks Results: 12 weeks 24 weeks – EOT 48 weeks – SVR

Baseline characteristics of the patients studied Male, n (%) 25 (79) Median age, years (range) 29 (19-39) Risk factors IVDU, cessation of drug use, n (%) Sexual exposure, n (%) 28 (88) 4 (12) Antiretroviral therapy, n (%) Yes No 26 (81) 6 (19) HIV-1 RNA, cp/ml Below 400, n (%) CD4 cells/μl Median (range) 413 (244-756) HCV genotype, n (%) 2 or 3 1 or 4 23 (72) 9 (28) HCV RNA, IU/ml 775300 (3.200 – 5.2x106) ALT, IU/l 98 (29 - 871) Clinical manifestations, n (%) 8 (25)

Patients with HCV-RNA negative results

Percentage of negative plasma HCV-RNA in patients with infection caused by genotype 1-4 and genotypes 2-3 HCV

Changes in aminotransferase levels during the 48 weeks of study

Conclusions This study shows good efficacy of PegINFα-2b and Ribavirin combination therapy for the treatment of acute HCV in HIV-infected patients with SVR – 75% The results of this study, if confirmed in a larger population, could justify the treatment of acute HCV in order to avoid the progression of the disease and to reduce the risk of HCV transmission

Acknowledgements We would like to thank Our patients and their families All medical and nursing staff of the hepatologic centre and the 25-th out-patient clinic who helped us to conduct this study All staff of Chair of Infectiuos Diseases and Chair of Internal Diseases, Peoples’ Friendship University of Russia, Moscow