Peginterferon monotherapy for the treatment of acute hepatitis C in HIV-coinfected patients

Le résumé fourni par la source

In recent years, in Western Europe, the incidence of acute hepatitis C virus (HCV) infection among HIV-infected men who have sex with men is increasing [1–3]. To date, only a small number of clinical trials have been performed and no evidence-based guidelines are available to guide the treatment of acute hepatitis C in HIV-coinfected patients. With much interest, we read the publication by Soriano et al. [4] on the updated recommendations from the HCV–HIV International Panel, published recently in this journal. After a short overview of acute hepatitis C in patients with chronic HIV infection, the authors recommended that these patients should be treated early with both pegylated interferon and ribavirin. They state that ‘addition of ribavirin ensures maximal clearance of HCV’. As this recommendation in merely based on an expert opinion, we would like to argue this and advocate that these patients could be treated with pegylated interferon solely, for reasons mentioned below. First, most available data about the treatment of acute hepatitis C come from trials performed in hepatitis C monoinfected patients. The first therapeutic trials in acute hepatitis C monoinfection, with varying interferon regimes and small numbers of included patients, showed a beneficial effect of treatment with responses varying between 25% and 91%. The first landmark trial by Jaeckel et al. [5], treating 44 patients with interferon alfa-2b for a total of 24 weeks, resulted in a sustained viral response rate (SVR) of 98%. More recently, a few trials [6–9] have shown that high response rates, varying between 72% and 94% can also be reached with peginterferon monotherapy. Up to now, there is no convincing evidence that addition of ribavirin to pegylated interferon will add any benefit [10]. Therefore, current guidelines for the treatment of acute hepatitis C monoinfection recommend peginterferon monotherapy instituted 12 weeks after seroconversion. What about the evidence in HIV/HCV-coinfected patients? In recent years, three prospective trials have been published on the treatment of acute hepatitis C in HIV-coinfected patients [11–13]. Both Dominguez et al. [12] and Gilleece et al. [13] have treated their patients with the combination of peginterferon and ribavirin whereas Vogel et al. [13] compared peginterferon monotherapy with peginterferon/ribavirin combination therapy. The SVRs reached in these trials were comparable (59–71%). Moreover, no difference in SVR rate was seen between patients treated with peginterferon/ribavirin combination therapy versus peginterferon monotherapy [13]. Therefore, in our opinion, there is no firm evidence at the moment to support the addition of ribavirin to peginterferon in the treatment of acute HCV infection in HIV-coinfected patients. A reason to withhold ribavirin is that it can be added to the treatment regimen in the later stages once chronic HCV is established, that is, in case of a nonresponse to early treatment or a relapse. Overall SVR rates in coinfected patients with acute HCV are substantially lower than in monoinfected patients (60 versus 90%). Therefore, a higher percentage of patients will fail treatment and will become chronic HCV carriers requiring re-treatment. Several trials in both HCV monoinfected and coinfected patients have shown that re-treatment with peginterferon and ribavirin combination therapy in (peg)interferon experienced patients results in much lower SVR rates than in (peg)interferon naïve patients [14–17]. Furthermore, it has been shown that, in chronic hepatitis C mono-infected patients, a less potent regime in the naïve chronic setting gives a higher chance of an acceptable SVR once re-treatment is necessary [18]. The addition of ribavirin in treating interferon nonresponders resulted in a higher SVR than re-treatment with interferon alone [19–21]. Moreover, HCV monoinfected patients who have a relapse after combination therapy need to be re-treated with higher doses of ribavirin and with prolonged courses of therapy [22,23]. Therefore, withholding ribavirin can be advantageous in order to optimize the chances of achieving a SVR once the peginterferon monotherapy has failed and the patient becomes a nonresponder or a relapser. Lastly, treatment of acute HCV infection in HIV coinfected patients with only peginterferon will result in less side effects (anaemia and thrombocytopenia), less interactions with antiretroviral agents and lower pill burden, resulting in a better compliance and higher chance to complete this therapy. In conclusion, on the basis of these arguments, we believe that, at present, there is not enough evidence to firmly support combination therapy with peginterferon and ribavirin for the treatment of acute HCV infection in HIV positive patients. Withholding ribavirin in the acute treatment phase can maximize the chances of an acceptable SVR in case the patient is a nonresponder or has a hepatitis C relapse and has to be re-treated without diminishing the initial chances of a high SVR.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.