1 / 16

Introduction (I)

Concomitant nevirapine therapy is associated with higher efficacy of pegylated interferon plus ribavirin among HIV/hepatitis C virus- coinfected patients.

samira
Download Presentation

Introduction (I)

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Concomitantnevirapinetherapyisassociatedwithhigherefficacy of pegylatedinterferon plus ribavirinamong HIV/hepatitis C virus-coinfectedpatients JA Mira, LF López-Cortés, E Vispo, C Tural, P Mallolas, E Ferrer, I de los Santos-Gil, P Domingo, H Knobel, F Téllez, M Crespo, A Rivero, E Ortega, JA Pineda on behalf of the VIRA-C Study Group

  2. Introduction (I) • It is known that some NRTIs, such as ddI, AZT and ABC, may decrease the efficacy and tolerability of HCV therapy due to different interactions and toxicities. • The information about whether PI and NNRTI influence SVR among coinfected patients is limited and contradictory. • The use of PIs during HCV therapy led to a worse rate of response to peg-IFN plus RBV in the Ribavic clinical trial. But, this association was not found in other studies performed in this population.

  3. Introduction (II) It has been reported that patients receiving NVP-based ART show lower plasma HCV-RNA load than those treated with PI- or EFV-containing regimens. This finding could have a positive influence on the response to HCV therapy among individuals taking NVP. It is critical to clarify if the use of NVP is associated with higher SVR rates to peg-IFN plus RBV treatment.

  4. Objective To compare the efficacy of peg-IFN plus RBV among HIV/HCV-coinfected patients taking TDF plus 3TC or FTC with either NVP or LPV/r.

  5. Methods (I) • Design:Retrospective multicenter study (2002-2009). • Setting:20 hospitals in Spain. • Inclusion criteria: • Older than 18 years. • Previously naive for HCV therapy. • On a three-drug antiretroviral regimen including TDF plus 3TC or FTC along with NVP or LPV/r at starting peg-IFN plus RBV.

  6. Methods (II) • HCV therapy: • peg-IFN α2a (180µg/week) or α2b (1.5µg/kg/week) plus RBV (800-1200mg/day). • Duration: Genotype 1-4: 48 weeks. Genotype 2-3: 24 or 48 weeks. • Statistical analysis: • Primary variable: SVR. • Sensitivity analyses: intention-to-treat and per-protocol. • Univariate and multivariate analysis (logistic regression) were performed to identify predictors of SVR.

  7. Results (I)Characteristics of the study patients (N=165) * Median (Q1-Q3).

  8. Results (II)Characteristics of the study patients (N=165) * Median (Q1-Q3).

  9. Results (III)SVR rates to peg-IFN plus RBV. Intention-to-treat analysis p=0.015 p=0.04 p=0.1 % n 27 71 94 43 60 34

  10. Results (IV)Causes of lack of SVR. Intention-to-treat analysis p=0.01 p=0.2 p=0.1 p=0.8 p=0.4 %

  11. Results (V) SVR rateaccordingtodifferents variables Baseline plasma HCV-RNA load Liver fibrosis stage ≥ 600.000 IU/ml <600.000 IU/ml F0-F2 F3-F4 p=0.8 p=0.01 p=0.2 p=0.2 % % 10 n 40 25 31 69 n 37 33 10 36 NVP LPV/r

  12. Results (VI)SVR to PEG-IFN plus RBV. Per-protocol analysis p=0.05 p=0.019 p=0.06 % n 44 57 160 13 101 59

  13. Results (VII)Factors associated with SVR. Multivariate analysis Odds ratio (CI 95%) HCV genotypes 2-3(p<0.001) TDF+3TC/FTC+NVP (p= 0.01) Exposure to HCV therapy ≥80% (p=0.01) 0 1 10 100 Variables without association with SVR: CDC Clinical Category C (p=0.1), HCV-RNA load (log IU/mL) (p= 0.08).

  14. Conclusions • HIV/HCV-coinfected patients who receive NVP respond better to peg-IFN plus RBV than those individuals receiving LPV/r. • Controlled clinical trials are warranted in order to confirm the impact of NVP on the efficacy of HCV therapy in the HIV-infected population.

  15. DiscussionImpact of NVP on HCV-RNA viral load HCV-RNA level among individuals receiving PI-, EFV- or NVP-based ART2 • It has been shown that HCV patients receiving NNRTIs, especially NVP, have lower HCV-RNA levels1,2. • HIV can induce HCV replication through TGF-beta1, which is produced in the liver in response to proinflamatory cytokines3. • NVP has been associated with higher decreases in levels of TNF-alpha receptor than other antiretroviral drugs4, which might decrease TGF-beta1 secretion in the liver and reduce HCV replication. p=0.012 1) Bani-Sadr F et al. AIDS 2007; 21: 1645 2) Mata R et al. EACS Conference 2009, Cologne, Germany. 3) Lin W et al. Gastroenterology 2008; 134:803–811 4) Virgili N et al. J Acquir Immune Defic Syndr 2009; 50: 552-553

  16. VIRA-C STUDY GROUP

More Related