5th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 8–11 July 2003, Le Meridien Montparnasse, Paris, France

ADVERSE EVENTS IN HIV/HCV-CO-INFECTED PATIENTS WITH INTERFERON α2B AND RIBAVIRIN (ANRS HC 02 – RIBAVIC TRIAL)

Antiviral Therapy 2003; 8:L4 (abstract W1)

C Perronne, F Bani Sadr, P Morand, F Lunel, E Rosenthal, S Pol, P Cacoub and F Carrat on behalf of the RIBAVIC Study Group
ANRS, Paris, France

BACKGROUND: The tolerability of anti-HCV treatments in HIV-HCV co-infected patients, with the possibility of drug interactions, is an important issue. The RIBAVIC study is comparing the tolerability and efficacy of a 48 week-course of the standard (IFNα2b: 3 MIU x3/week, n=210 patients) to the pegylated (PEG-IFNα2b: 1.5 μg/kg x1/week, n=206 pts) interferon + ribavirin combination (800 mg/day, ≈12 mg/kg/day).

METHODS: A randomized, multicentre, parallel-group, open-label trial. Inclusion criteria were: HCV RNA-positive and abnormal liver histology, CD4>200, stable HIV RNA, stable highly active antiretroviral therapy (HAART) or off HAART. Side effects were recorded, including complications due to the combination of anti-HIV and anti-HCV drugs, such as mitochondrial cytopathy.

RESULTS: The 416 patients (40 years, 73% male, 79% intravenous drug users) were given HAART in 80%; they had a mean CD4 cell count of 515 ±228/ml, HIV RNA <200 in 60% (mean viral load in others: 3.48 ±0.8 logs) and belonged to the CDC class A, B and C in 56, 28 and 16%, respectively. The mean pre-treatment Metavir score was A 1.8 ±0.7, F 2.3 ±1.0, 39% of pts had F3-F4, of which 16% had sustained normal ALT. Baseline variables at entry were not different between groups. Treatment discontinuation has been reported in 145 patients (38% in PEG group, 32% in INF group) and severe adverse events in 122 (29%) (48 IFN and 74 PEG). Of 400 patients receiving at least one dose of HCV treatment, 11 developed symptomatic mitochondrial toxicity (SMT). Hyperlactataemia in six cases: general weakness (five), weight loss (four), nausea (two), rapid lipoatrophy (two), dyspnea (one), peripheral neuropathy (one), acidosis (two). Pancreatitis in five cases: abdominal pain (four), nausea/vomiting (two), lipase ≥10N (five), hyperlactataemia (one), pancreatic CT scan lesions (one). The incidence of SMT was 27.5/1000 patients.year (34.1/1000 when combination with HAART, 0 without HAART). In multivariate analysis, SMT was associated with didanosine use (OR=44, 95% CI: 7-Inf) but not with stavudine. A significant decrease (P<0.001) was observed at the early stage of treatment (week 12) in Hb (IFN: -1.5 g/dl; PEG: -1.8 g/dl, P=0.04 ), neutrophils (IFN: -693; PEG: -1298, P=0.0035), lymphocytes (IFN: -317; PEG: -542, P=0.12, including -44 CD4 and -69 CD4, P=0.21) and platelets (IFN: -16000, PEG: -33000, P=0.02).

CONCLUSIONS: In co-infected patients, anti-HCV treatment is less tolerated leading to a high rate of treatment interruption. Co-administration of ribavirin and didanosine should be avoided.

Presenting author: C Perronne

2003-07-08
W1

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