Session 105Poster Presentations HCV: Therapeutic Progress Session Day and Time: Wednesday 1:30 - 3:30 pm Room: Hall B
841 Final Results of Daily vs 3-times Weekly Interferon alpha-2b plus Ribavirin for the Treatment of Hepatitis C Infection in HIV-infected Persons: A Multi-center, Randomized Open-label Study M. Sulkowski1, F. Felizarta2, J. Slim3, D. Dieterich4, R. Goodman*5, L. Ball5 1Johns Hopkins Med Inst, Baltimore, MD; 2Bakersfield, NJ; 3Newark, NJ; 4Mt Sinai Sch of Med, New York, NY; and 5Hepatitis Resource Network, Puyallup, WA
Background: Hepatitis C (HCV) is an opportunistic infection that causes substantial morbidity and mortality in HIV-infected patients (pts). Few studies have evaluated the safety and efficacy of Interferon (IFN)/Ribavirin (RBV) in co-infected patients. We present the final results of a randomized, controlled trial of IFN/RBV use in co-infection.
Objective: To assess the efficacy and safety of RBV with Daily (QD) or 3 Times Weekly (TIW) IFN for chronic HCV in HIV-infected pts.
Methods: Randomized, controlled, open-label, multicenter (68 sites) trial comparing IFN 3 mIU QD vs TIW + RBV (800 g/d) for 48 wks in 180 IFN/RBV-naïve, HIV-infected pts with compensated liver disease on stable antiretroviral therapy (ART). Those with active OIs, active substance abuse, severe psychiatric disease, or CD4 < 100/mm3 were excluded. Efficacy (HCV RNA) was assessed at treatment (Tx) wks 12, 24, and post-Tx wk 24. Safety assessments included incidence of AEs, rate of dose modification/discontinuation. CD4 count and HIV RNA levels were monitored. The Chi-squared test was used to test differences in proportions.
Results: Patient characteristics (QD/TIW): mean age, 44/44 yrs; male, 78/74%; Caucasian, 58/44%; genotype 1, 78/80%; ART, 89/82%, mean CD4, 551/533/mm3, mean HIV RNA, 1,531/3,698 c/mL. A total 162 (79 QD/83 TIW) were eligible for the intent-to-treat (ITT) analysis. Discontinuation for AEs was similar in both groups (p = 0.24); however, more pts taking QD IFN completed of 48 wks of Tx (30.0% QD vs 12.0% TIW, p = 0.0003) since 43.4% of pts taking TIW IFN stopped due to virologic failure compared to only 20.2% of those taking QD IFN (p = 0.0003). HCV RNA response (undetectable < 600 IU/mL) was assessed at week 12 (EVR) and wk 24 post-Tx (SVR). On-treatment results: EVR QD 44.3%/TIW 17.1% (p = 0.004); SVR: QD 42.9%/TIW 28.% (p = 0.03). Intention to treat results: EVR: QD 32.9% /TIW 13.3%; SVR: QD 9.3%/TIW 4.3% (note: missing data = failure). No significant effect was seen on HIV RNA levels; absolute CD4 fell in both groups (QD > TIW), but no decrease in CD4% was observed. EVR was a strong predictor of SVR (90.9% sensitivity, NPV 93.9%).
Conclusions: Both EVR and SVR were significantly greater in HIV-infected pts taking QD IFN/RBV than in those taking TIW IFN/RBV. The adverse event rate was similar in both groups; however, more pts taking QD IFN completed Tx. However, the attrition rate for both Tx arms was substantial, and the intention-to-treat SVR rates observed were low.
