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• W2058409846 abstract "We read with interest the article from Landau et al. [1] on the efficacy of the combination of interferon plus ribavirin for treating chronic hepatitis C virus (HCV) in HIV-infected individuals. After 6 months of therapy, 10 out of 20 (50%) recruited patients cleared HCV RNA. The authors thus concluded that the treatment of chronic hepatitis C should be recommended in HCV-HIV co-infected individuals. Although we would generally agree, several aspects of the study design and the population analysed by Landau et al. [1] limit the interpretation of their data, and warrant further clarification. Otherwise, their message could be misinterpreted. First, the definition of response when treating chronic hepatitis C usually requires both the normalization of liver enzymes and the clearance of HCV RNA [2]. These parameters need to be examined 6 months after stopping treatment in order to define the sustained response [2]. Landau et al. [1] used a negative HCV-RNA result when patients were still on treatment to consider the efficacy of interferon plus ribavirin. Therefore, nearly half the subjects considered to be responders by the authors probably relapsed thereafter [2–4]. Landau et al. [1] should have waited for 6 months after completing treatment to report their data. Otherwise their results can not be compared with those obtained in trials conducted in HIV-negative subjects with chronic hepatitis C. Second, the authors stated that all but one of their patients had less than 200 CD4 cells/μl at baseline. However, an average of 350 cells/μl was shown in Table 1. So far, the treatment of chronic hepatitis C should not be recommended for individuals with less than 200 CD4 cells/μl [5,6]. In the era of highly active antiretroviral therapy, individuals having less than 200 CD4 cells/μl should first be considered for treatment against HIV, and in those already on antiretroviral drugs, the prevention of classic opportunistic infections must remain the primary goal. In these individuals, the long-term risk of progression to cirrhosis should not be a major concern. Moreover, the rate of response to interferon falls as the CD4 cell count decreases [7], and the risk of lymphocytopaenia can even make worse the outcome of these patients [8,9]. Third, the population examined by Landau et al. [1] was too heterogeneous: 45% of subjects were cirrhotic patients, and 20% had received a previous course of interferon without success, being the remaining subjects naive for interferon. Moreover, the treatment of individuals with HCV genotype 1 was allowed for only 6 months instead of extending it to one year, as is usually recommended [2–4]. All these circumstances might have compromised the benefit of the interferon plus ribavirin combination. A trial conducted in a more homogeneous population (i.e. naive, non-cirrhotic patients) would have provided more useful information. Fourth, there was a surprising lack of drop-outs in the Landau trial. In HIV-negative individuals, rates of discontinuation close to 20% are commonly reported when using interferon plus ribavirin [3,4]. The use of concomitant medications, mainly antiretroviral agents, as well as the presence of some physical or psychological abnormalities, should all have negatively influenced the tolerance to interferon or ribavirin in HIV-infected patients. In a pilot trial conducted at our institution [10], in which interferon plus ribavirin was administered to 18 HIV-HCV co-infected patients who did not respond to a previous course of interferon alone, the rate of sustained response (6 months after stopping therapy) was 45% among those who completed 6 months on therapy. However, treatment discontinuation (suicidal ideation, anaemia, voluntary withdrawal) occurred in seven patients (39%). Although the report by Landau et al. [1] might have several pitfalls, we would like to underline that the treatment of chronic hepatitis C in HIV-infected patients must be considered for the appropriate candidates. So far, those should be individuals with CD4 cell counts above 300 cells/μl, undetectable plasma HIV RNA levels if on highly active retroviral therapy, or below 10 000 HIV-RNA copies/ml if not [6]. The use of zidovudine should be discouraged, because the risk of anaemia will be enhanced by taking ribavirin concomitantly. Moreover, there seems to be a competitive inhibition between thymidine analogues (zidovudine, stavudine) and ribavirin, which might hamper their respective clinical activity [11]. Preliminary encouraging data, such as that provided by Landau et al. [1] and our group, should promote the design of prospective, randomized, multicentre trials, in which both the safety and the efficacy of interferon plus ribavirin may be examined more appropriately. Moreover, the availability of the new pegylated form of interferon (administered once a week) [12,13] will probably impact more favourably on the tolerance and success of the treatment for chronic hepatitis C. Vincent Sorianoa Rafael Rodríguez-Rosadoa Mayte Pérez-Olmedaa Miriam Romerob Javier García-Samaniegob" @default.
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• W2058409846 title "Interferon plus ribavirin for chronic hepatitis C in HIV-infected patients" @default.
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• W2058409846 doi "https://doi.org/10.1097/00002030-200010200-00027" @default.
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