Several recent studies have shown a rising incidence of apparently sexually transmitted acute hepatitis C virus (HCV) infection in Western Europe, primarily among HIV positive men who have sex with men (MSM)[1,2,3]. To date, however, there is limited research and no evidence-based guidelines on the treatment of acute hepatitis C in HIV positive patients.

The latest recommendations from the HCV-HIV International Panel, published in the May 31, 2007 issue of AIDS, advise that coinfected patients should be treated early with pegylated interferon plus ribavirin [4]. Authors Vincent Soriano and colleagues state that, "The addition of ribavirin ensures maximal clearance of HCV."

However, a group of Dutch researchers argues against this conclusion in the current issue of AIDS (July 11, 2008), noting that this recommendation is based on expert opinion rather than hard data. The authors instead advocate that HIV positive individuals with acute hepatitis C could be treated with pegylated interferon monotherapy, for reasons that are summarized below.

First, wrote the authors, "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 researchers then point out that the first landmark acute HCV trial by Elmar Jaeckel and colleagues[5], in which 44 patients were treated with interferon alfa-2b [Intron A] monotherapy for a total of 24 weeks, resulted in a sustained virological response rate (SVR) of 98%.

More recently, a few trials have shown that similarly high response rates, ranging between 72% and 94%, can also be attained using pegylated interferon (Pegasys or PegIntron) monotherapy.

"Up to now," stated the authors, "There is no convincing evidence that addition of ribavirin to pegylated interferon will add any benefit. Therefore, current guidelines for the treatment of acute hepatitis C monoinfection recommend peginterferon monotherapy instituted 12 weeks after seroconversion."

What Is the Evidence in HIV-HCV Coinfected Patients?

In recent years, noted the Dutch authors, 3 prospective trials have been published on the treatment of acute hepatitis C in HIV-HCV coinfected patients. Both Dominguez and colleagues[6] and Gilleece and colleagues[7] have treated patients with combination pegylated interferon plus ribavirin, while Vogel and colleagues[8] others compared pegylated interferon monotherapy versus pegylated interferon/ribavirin combination therapy.

"The SVRs reached in these trials were comparable (59-71%)," wrote the Dutch authors. In addition, they noted that no difference in SVR rates was seen between patients treated with pegylated interferon/ribavirin combination therapy versus pegylated interferon monotherapy. "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," they wrote.

The authors suggest that another reason for delaying use of ribavirin is that it can be added to the treatment regimen at a later stage if chronic HCV becomes established despite early therapy, that is, in case of non-response to early treatment or relapse.

"Overall SVR rates in coinfected patients with acute HCV are substantially lower than in monoinfected patients (60 versus 90%)," they stated," and 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 HIV-HCV coinfected patients have shown that re-treatment with pegylated interferon plus ribavirin combination therapy in patients previously treated with conventional or pegylated interferon results in much lower SVR rates compared with treatment-naive individuals [9-12].

Furthermore, studies in chronic hepatitis C monoinfected patients have shown that "a less potent regime in the naive chronic setting gives a higher chance of an acceptable SVR once re-treatment is necessary," the authors wrote. "The addition of ribavirin in treating interferon nonresponders resulted in a higher SVR than re-treatment with interferon alone."

In addition, regarding ribavirin, they noted that HCV monoinfected patients who experience a relapse after combination therapy need to be re-treated with higher doses of ribavirin and with prolonged courses of therapy. Therefore, they argued, "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 non-responder or a relapser."

Further, the authors wrote, treatment of acute hepatitis C in HIV-HCV coinfected patients with pegylated interferon monotherapy "will result in less side effects (anemia and thrombocytopenia), less interactions with antiretroviral agents, and lower pill burden, resulting in a better compliance and higher chance to complete this therapy."

Finally, they concluded, "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."

They continued, "Withholding ribavirin in the acute treatment phase can maximize the chances of an acceptable SVR in case the patient is a non-responder or has a hepatitis C relapse and has to be re-treated without diminishing the initial chances of a high SVR."

Department of Internal Medicine and Infectious Diseases, Netherlands; Eijkman-Winkler Institute for Microbiology, Infectious Diseases and Inflammation, University Medical Center Utrecht, Utrecht, Netherlands; Department of Internal Medicine, Gelre Ziekenhuizen, Apeldoorn, Netherlands.

7/08/08

Reference
J E Arends, IM Schrover, CG Schaar, and others. Peginterferon monotherapy for the treatment of acute hepatitis C in HIV-coinfected patients [Correspondence]. AIDS 22(11): 1381-1382. July 11, 2008.