[960] INTERFERON ALPHA AND RIBAVIRIN THERAPY FOR CHRONIC HEPATITIS C IN HIV-INFECTED PATIENTS (GESIDA 28-02 STUDY)

2nd International AIDS Society Conference on HIV Pathogenesis and Treatment

Paris, France - July 13 - 16, 2003

[TITLE:] INTERFERON ALPHA AND RIBAVIRIN THERAPY FOR CHRONIC HEPATITIS C IN HIV-INFECTED PATIENTS (GESIDA 28-02 STUDY)

[AUTHOR(S):] J Berenguer¹, J Gonzalez², P Miralles¹, C Quereda³, PMA Von-Wichman⁴, P Labarga⁵, B Mahillo⁶ and the GESIDA 28/02 Study Group
¹Gregorio Maranon; ²Hosp La Paz; ³Hosp Ramon y Cajal; ⁴Hosp Donosita; ⁵Hosp Donostia; and 6 AEC GESIDA, Spain

IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 960
Antiviral Therapy 2003; 8(Suppl. 1):S455

[ABSTRACT:] Objective: To analyse therapeutic efficacy and safety of interferon a (IFN) and ribavirin (RBV) for chronic hepatitis C (CHC) in HIVinfected patients (pt).

Patients and methods: Design: Observational multicentre cohort study. Patients: 132 pt (from 6 hospitals affiliated to GESIDA) with HIV and confirmed CHC [increased ALT, (+) PCR for HCV and (.) HBsAg]. Male/female: 103/29. Median age 37 y. Median weight 69 kg. HIV data: IVDA 116 pt. CDC category, A: 66 pt, B: 36 pt, C: 29 pt. Median nadir CD4: 216/μl. Median baseline CD4: 510/μl. HIV viral load <50 copies/ml: 66 pt. HAART: 98 pt (AZT: 16 pt, ddI: 18 pt, d4T: 53 pt, ddI+d4T: 21 pt). CHC data: Genotypes, 1: 65 pt, 2: 4 pt, 3: 52 pt, 4: 10 pt, unknown 1 pt. HCV viral load >850,000 UI: 70 pt. Never drank alcohol (>50 g/d) 68 pt. Liver biopsy (116 pt), F0: 4.5%, F1: 20.5%, F2: 18.9%, F3: 32.6%, F4: 11.4%. Treatment: IFN γ-2b: 114 pt; IFN γ-2a: 18 pt. IFN 3 MU 3 times/wk: 119 pt, and IFN >3 MU 3 times/wk (for induction): 13 pt RBV median dose: 14.63 mg/kg. HCV PCR was performed at 24 wk, if (+) IFN-RBV therapy was stopped, if (μl) therapy was prolonged to 48 wk.

Results: Efficacy: Sustained virological response (SVR) by ITT analysis: all genotypes 28 pt (21.2%), genotypes 1.4: 9 pt (12%), genotypes 2.3: 18 pt (32%). By logistic regression, genotype was the only variable associated with SVR; OR of not achieving SVR by ITT for genotypes 1.4 vs 2.3: 3.4 (CI 95% 1.21.9.58) P=0.021. Safety: Severe adverse events (AE) developed in 19 pt (14%): psychiatric disorders 4 pt, pancreatitis/lactic acidosis 4 pt, hepatic decompensation 3 pt, lipoatrophy 2 pt, other AE 6 pt. Fifteen 15 pt (11%) discontinued IFN-RBV due to AE. Two pt died during IFN-RBV therapy: sepsis and lactic acidosis, one each. By logistic regression, d4T+ddI therapy was the only variable associated with discontinuation of IFN-RBV due to AE: OR for d4T+ddI vs no d4T+ddI: 4.44 (CI 95% 1.38.14.27) P=0.012.

Conclusions: Our data suggest that the therapeutic efficacy of IFN-RBV for CHC in HIV-infected pt is substantially lower than that reported in clinical trials in non-HIV-infected pt. Genotype was the only baseline predictor of treatment outcome. The combination of IFN-RBV may cause severe AE due to drug interactions with antiretrovirals, particularly in patients treated with d4T+ddI.

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