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Pegylated interferon alpha-2b plus ribavirin as therapy for chronic hepatitis C in HIV-infected patients

Callens, Stevena,b; Bottieau, Emmanuela,b; Michielsen, Peterc; Colebunders, Roberta,b


aDepartment of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; bTropical Diseases Unit and cDepartment of Gastroenterology, University Hospital, Antwerp, Belgium.

See also pp. 1, 59, 67, 75, 121

Received: 6 June 2003; accepted: 11 August 2003.

Pérez-Olmeda et al. [1] reported that pegylated interferon alfa-2b (peg-IFN) plus ribavirin therapy cured one third of patients co-infected with HIV and hepatitis C virus (HCV), and that such therapy is relatively well-tolerated. In only two out of the 68 patients (3.1%) was a decline in the absolute CD4 lymphocyte count greater than 33% observed. In none of them was a change in the CD4 lymphocyte percentage seen.

We recently observed an HIV–HCV co-infected patient treated with peg-IFN/ribavirin in which the CD4 lymphocyte count fell from 0.429 × 109/l (28.1%) to 0.029 × 109/l (9%). These low levels persisted despite a sustained undetectable HIV viral load, even after the HCV therapy was stopped.

A 49-year-old, HIV–HCV co-infected man, with compensated liver cirrhosis (Child–Pugh class A) was started on peg-IFN (1.50 μg/kg per week) and ribavirin (1200 mg once a day). His body weight was 100 kg. For HIV infection he was treated with abacavir, lamivudine and zidovudine. At the start of the peg-IFN/ribavirin treatment his CD4 lymphocyte count was 0.429 × 109/l (28.1%) and his viral load was less than 50 copies/ml plasma. Two months after the initiation of the peg-IFN/ribavirin, he developed anaemia (haemoglobin 9.5 g/dl) and thrombocytopenia (40 × 109 /l). For this reason the HCV treatment was continued at a reduced dosage (peg-IFN 100 μg a week, ribavirin 600 mg once a day). Ultimately, both drugs had to be discontinued after 12 weeks when severe anaemia developed (haemoglobin 7.4 g/dl). The HCV-RNA (polymerase chain reaction test) level at that time was negative. One month later when the haemoglobin level was 8.7 g/dl and the platelet count was 99 × 109 /l, peg-IFN monotherapy was restarted. After the reintroduction of peg-IFN, a severe Coombs-positive anaemia developed (haemoglobin 5.1 g/dl) and thrombocytopenia persisted (72 × 109 /l). Zidovudine was switched to stavudine and the peg-IFN was stopped. His CD4 lymphocyte count at that time was 0.275 × 109/l (28.1%). Finally, high-dose steroid therapy reversed the anaemia and thrombocytopenia, but the patient developed diabetes mellitus requiring insulin therapy. His CD4 lymphocyte count fell during peg-IFN therapy, and continued to decline to a level of 0.029 × 109 cells/l (9.0%) 3 months after this therapy was stopped. Ten months after the start of the peg-IFN/ribavirin therapy the patient died as a result of invasive pulmonary aspergillosis.

Interferon potentially induces haemolytic anaemia, thrombocytopenia, leucopenia with neutropenia and a decrease in the CD4 lymphocyte cell count [2–4]. This decrease in the CD4 lymphocyte count during interferon therapy has been attributed to autoimmunity [5,6]. Generally, a spontaneous recovery in the CD4 lymphocyte count is observed after stopping interferon treatment. However, in our patient, despite a sustained undetectable HIV viral load, his CD4 lymphocyte count continued to drop after the termination of HCV therapy.

The decision to discontinue peg-IFN/ribavirin treatment because of haematological toxicity, in HIV–HCV co-infected patients should be made sufficiently early, in order to avoid a prolonged low CD4 lymphocyte count and an increased risk of developing opportunistic infections.

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© 2004 Lippincott Williams & Wilkins, Inc.