Treatment of chronic hepatitis C with peginterferon and ribavirin in patients with HCV/HIV co-infection S. Fedorchenko, MD

Transcription

1 Treatment of chronic hepatitis C with peginterferon and ribavirin in patients with HCV/HIV co-infection S. Fedorchenko, MD GI «L.V. Gromashevsky Institute of Epidemiology and Infectious Diseases of the National Academy of Medical Sciences of Ukraine»

2 НВV and HCV markers in risk groups in Ukraine Detected infection markers Survey groups (n) HBV HCV HBsAg anti-нвс anti-hcv Total % ± mp Total % ± mp Total % ± mp Patients with STD (1,274) ± ± ±0.9 Sex workers (1,606) ± ± ±1.2 HIV-infected people (1,404) ± ±1.3 1, ±1.0 PWID (1,429) ± ± ±1.3 Persons deprived of liberty (1,533) ± ± ±1.3 GI «L.V. Gromashevsky Institute of Epidemiology and Infectious Diseases of the National Academy of Medical Sciences of Ukraine»,

3 Study objective: to determine the efficacy of therapy with pegylated interferons (Peg-IFN) in combination with ribavirin (RBV) in patients with HCV/HIV co-infection Study object HCV/HIV co-infection

4 Study tasks: To evaluate the efficacy and tolerance of therapy with Peg-IFN + RBV in patients with НСV/HIV coinfection To review the efficacy of antiviral therapy (AVT) depending on baseline level of HCV-RNA viremia and HCV genotype in patients with НСV/HIV coinfection To determine the efficacy of AVT depending on HIV infection stage, СD4+ count and ART

5 Group characteristics: HCV/HIV The study enrolled patients with confirmed diagnosis of HIV infection (by IFA with confirmation by IB) and HCV infection: Anti-HCV+, RNA-HCV+ Clinical stage of HIV infection (WHO): 1-7.7% (10/130) 2-9.2% (12/130) % (65/130) % (43/130)

6 Group characteristics (n = 130) Gender males 68% (88/130) females 32% (42/130 Age (years) 33 (CI 95%; 32-34) HIV infection route: PWID RNA HCV blood plasma levels: > IU/mL HCV genotype: 1 81% (105/130) sexual 19% (25/130) 48% (63/130) < IU/mL 52% (67/130) 52.3% (68/130) % (8/130) 40.0% (52/130) 4 Antiretroviral therapy (ART): 1.5% (2/130) 96 (76.8%)

7 Group characteristics: ART ART concomitantly with AVT received by: 69.2% (90/130) depending on NRTI component: depending on NNRTI/PI/INSTI platforms: - AZT containing 62.2% (56/90) - TDF containing 37.8% (34/90) - NNRTI 22.2% (21/90) - PI 76.7% (68/90) - INSTI 1.1% (1/90) АRТ administered during AVT 4.6% (6/130) depending on NRTI component: depending on NNRTI/PI/INSTI platforms: - AZT containing (1/6) - TDF containing (5/6) - NNRTI (2/6) - PI (4/6)

8 Progress of the study of efficacy of therapy with pegylated interferons in combination with ribavirin in patients with HCV/HIV co-infection 130 patients Initiated the treatment 98 (75.4%) Completed 24 weeks of AVT 89 (68.5%) Completed 48 weeks of AVT 41 (31.5%) Failed to complete the treatment course 31 (23.8%) Virological failure 10 (7.7%) Adverse reactions

9 Peg-IFN+RBV: SVR in patients with HIV/HCV co-infection depending on demographic parameters and route of HIV infection p = 0,062 p = 0,107 p = 0,122 % of patients with SVR 67,0% 68,9% 64,8% 55,1% 50,0% 48,0% 59/88 21/42 42/61 38/69 12/25 68/105 males females <33 years >33 years non-pwid PWID

10 Peg-IFN+RBV: SVR in patients with HIV/HCV co-infection depending on genotype and viral load in 1 HCV genotype p = 0, ,7% % of patients with SVR 61,5% 32,4% p = 0,066 55,9% 80/130 11/34 19/34 49/60 gen. 1,2,3,4 gen. 1RNA gen. 1RNA gen. 2/3

11 Peg-IFN+RBV: SVR in patients with HIV/HCV co-infection depending on CD4 lymphocytes count at AVT start p = 0,482 % of patients with SVR 61,5% 60,2% 68,2% 80/130 65/108 15/22 All CD4 > 350 cells/mcl CD4 < 350 cells/mcl

12 Peg-IFN+RBV: SVR in patients with HIV/HCV co-infection depending on HIV infection clinical stage p = 0,482 % of patients with SVR 68,2% 61,5% 60,2% 80/130 15/22 65/108 All Clinical Stage 1, 2 Clinical Stage 3, 4

13 Median absolute CD4 counts progress in patients after 48 weeks Peg-IFN+RBV p = 0,0001 p = 0,002 p = 0,182 CD4+, cells/mm p = 0, p = 0,295 p = 0,03 p = 0,627 p = 0,001 p = 0, Treatment Weeks

14 Median relative CD4 counts progress in patients after 48 weeks Peg-IFN+RBV p = 0,006 p = 0,0001 p = 0,012 CD4+, % p = 0,112 p = 0,008 p = 0, ,5 p = 0, p = 0, Treatment Weeks

15 SVR in patients with HIV/HCV co-infection depending on ART co-administered with Peg-IFN+RBV p = 0,729 % of patients with SVR 61,5% 58,8% 62,2% 80/130 20/34 56/90 All Only Peg-IFN+RBV ART+Peg-IFN+RBV

16 Peg-IFN+RBV: SVR in patients with HIV/HCV co-infection depending on NRTI-component of ART regimens p = 0,01 p = 0,08 83,3% % of patients with SVR 62,2% 67,6% 47,4% 56/90 18/39 23/34 15/18 ART+Peg-IFN+RBV AZT-containing TDF-containing AZT substituted

17 Peg-IFN+RBV: SVR in patients with HIV/HCV co-infection depending on NNRTI-or PI platforms of ART regimens p = 0,599 % of patients with SVR 66,7% 60,3% 14/21 41/68 NNRTI PI

18 CONCLUSIONS 1. Efficacy of Peg-IFN+RBV for chronic HCV infection treatment evaluated on the basis of reaching SVR in patients with HIV/HCV co-infection does not depend on gender, age, route of HIV infection and the history of use of injection drugs 2. Chance of reaching SVR in patients with HIV/HCV coinfection depends on HCV genotype. The highest positive response rates were observed in patients with HCV genotypes 2 and 3 3. Relative risk of not reaching SVR in patients with HIV/HCV co-infection genotypes 1 and 4 was 3 times higher than in patients with HCV genotypes 2 and 3

19 CONCLUSIONS 2 4. No statistically significant effects of baseline HCV viral load on reaching SVR were found out 5. No statistically significant effects of absolute CD4 count at AVT (Peg-IFN+RBV) start in group assignment, no statistically significant relationship was determined between clinical stage of HIVinfection and efficacy of treatment for HCV infection evaluated on the basis of reaching SVR

20 CONCLUSIONS 3 6. No statistically significant effects on the efficacy of treatment of HCV infection evaluated on the basis of reaching SVR, ART regimens depending on NNRTIand PI-platforms were found out 7. Statistically significant effects on Peg-IFN+RBV HCV treatment efficacy were determined in case of substitution of ART AZT-containing regimen onto TDFcontaining regimen as evaluated on the basis of SVR in patients with HIV/HCV co-infection