Incidence of Anaemia and Impact on Sustained vVirological Response in HIV/HCV-Coinfected Patients Treated With Pegylated Interferon Plus Ribavirin

M. Núñez; A. Ocampo; K. Aguirrebengoa; M. Cervantes; A. Pascual; S. Echeverria; V. Asensi; P. Barreiro; J. Garcia-Samaniego; V. Soriano

Disclosures

J Viral Hepat. 2008;15(5):363-369. 

In This Article

Summary and Introduction

Ribavirin (RBV) exposure is important for maximizing the response to chronic hepatitis C virus (HCV) therapy. However, RBV-associated haemolytic anaemia may force dose reductions or even treatment discontinuation. The use of zidovudine might further increases the risk of anaemia in HCV/HIV-coinfected patients. The predictors of anaemia were examined in PRESCO, a large trial conducted in HIV/HCV-coinfected patients treated with pegylated interferon alpha-2a 180 μg/week plus RBV 1000-1200 mg/day. Measurements included maximal decrease in haemoglobin (Hb) throughout treatment, drops in Hb to <10 (moderate) or to <8.5 g/dL (severe), and premature RBV discontinuation because of anaemia. Finally, the impact of anaemia on sustained virological response (SVR) was assessed. Moderate or severe anaemia occurred, respectively, in 51 (13%) and 13 (3.3%) of 389 patients included in the study. Lower baseline Hb [RR: 0.14 (95% CI 0.07-0.27); P < 0.0001] and greater Hb drops during the first 4 weeks of therapy [RR: 4.74 (95% CI 2.95-7.60); P < 0.0001] were independent predictors of moderate anaemia at any time point in the multivariate analysis. Mean drops in Hb from baseline to week 4 were significantly greater in patients receiving zidovudine compared with other drugs (-3.09 vs-2.3 g/dL; P < 0.001). Lower baseline Hb [RR: 0.33 (95% CI 0.11-0.95); P = 0.04] and maximal Hb drops during treatment [RR: 2.48 (95% CI 1.33-4.59); P = 0.004] predicted treatment discontinuation because of anaemia. However, maximal Hb drops, development of moderate-severe anaemia and RBV dose reductions were comparable among patients who achieved SVR and those who did not. Lower baseline Hb predicts maximal drops in Hb and development of anaemia in HIV/HCV-coinfected patients treated with pegylated interferon plus RBV. The use of zidovudine is associated with greater Hb declines at week 4. However, severe anaemia is relatively infrequent and seems not to have much impact on SVR. Given the availability of alternative antiretroviral drugs, it is advised to avoid zidovudine while receiving anti-HCV treatment.

The addition of ribavirin (RBV) to pegylated interferon (pegIFN) has shown to significantly improve sustained virological response (SVR) in patients with chronic hepatitis C virus (HCV) infection and combination therapy is currently the standard treatment for chronic hepatitis C.[1] Insufficient exposure to RBV is followed by suboptimal response to anti-HCV therapy.[1]

Haemolytic anaemia is a side effect of RBV.[2,3] Its extent largely depends on plasma concentrations of the drug.[4] This is also the case in HCV/HIV-coinfected individuals,[5] in whom other factors may also contribute to anaemia. In particular, the use of zidovudine (AZT) as part of highly active antiretroviral therapy (HAART) may enhances the risk of anaemia, as a result of bone marrow impairment.[6,7] Herein, we have examined the rate and predictors of the development of anaemia in a large therapeutic trial conducted in HCV/HIV-coinfected patients, as well as its impact on SVR.

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