Reply to Bruno et al.: update to HIV–hepatitis C virus consensus guidelines
Soriano, Vincenta; Cacoub, Patriceb; Cargnel, Antoniettac; Mauss, Stefand; Sulkowski, Marke; Hatzakis, Angelosf; Rockstroh, Jurgeng; Puoti, Massimoh; Dieterich, Douglasi
aService of Infectious Diseases, Hospital Carlos III, Madrid, Spain; bService de Medecine Interne, Hôpital de la Pitié-Salpetrière, Paris, France; cDivisione di Malattie Infettive, Ospedale Luigi Sacco, Milan, Italy; dCenter for HIV and Hepatogastroenterology, Düsseldorf, Germany; eDivision of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA; fDepartment of Hygiene and Epidemiology, Athens University Medical School, Athens, Greece; gDepartment of Medicine, University of Bonn, Bonn, Germany; hClinica di Malattie Infettive e Tropicali, Spedali Civili, Brescia, Italy; and iDepartment of Medicine, Mount Sinai Medical Center, New York City, NY, USA.
Received: 4 June 2004; accepted: 4 June 2004.
We would like to thank Bruno and colleagues for their interest in the updated recommendations from the HIV–HCV International Panel published in the journal earlier this year . The authors mentioned that there are some incorrect figures in two of the studies recorded in the table, in which the results of trials using pegylated interferon (peg-IFN) plus ribavirin are summarized. However, the two trials were ongoing at the time the manuscript was submitted for publication. Two of the main investigators of those trials were members of the panel and they updated their results at the time the manuscript was written, which explains the apparent discordances found by Bruno et al. looking at abstracts presented at older conferences. The final results of one of those studies, the French RIBAVIC trial, were recently presented at the 11th Conference on Retroviruses and Opportunistic Infections . Moreover, more updated results from the other study were presented at the Digestive Disease Week, 2003, which took place in Orlando in May 2003. In that Italian trial, 69 patients were randomly assigned to receive peg-IFN plus ribavirin; the virological response at 24 weeks had been reached by 19 of the 34 co-infected patients (56%) treated until that moment .
The authors ended their comments highlighting the results of the APRICOT trial, another study presented at the latest Retrovirus Conference, in which peg-IFN plus ribavirin was used for treating hepatitis C virus (HCV) in HIV-co-infected patients . Although the results from that trial are the best obtained so far, Bruno et al. should not ignore the fact that the response rates are much lower than in HCV-monoinfected patients. Moreover, other studies in co-infected individuals have provided even lower response rates using similar treatment regimens, including another two trials presented at the 11th Conference on Retroviruses and Opportunistic Infections (see Table 1). We would like to take the opportunity in this letter to update and discuss briefly the most recent data on this matter.
The ACTG 5071 included 66 co-infected patients from several US centres, who were treated with a fixed dose of 180 μg/week of peg-IFN alpha-2a (Pegasys) plus ribavirin . All subjects began ribavirin at doses of 600 mg per day and increased up to 1000 mg at week 12 if the tolerance was acceptable. In this trial, 77% of patients carried HCV genotype 1, which tended to respond less well to HCV therapy. End-of treatment response was reached by 41% of patients, but sustained virological response was only maintained by 27% (14% in patients with HCV genotype 1 and 73% in patents with other genotypes).
The previously mentioned RIBAVIC trial was a multicentre French study conducted by the Agence Nationale de Recherche sur le SIDA, in which 205 co-infected patients were treated with a weight-adjusted dose (1.5 μg/kg per week) of peg-IFN alpha-2b (PegIntron) plus a fixed dose of 800 mg ribavirin . Overall, 27% of patients reached a sustained virological response (15% for HCV genotypes 1 or 4, and 43% for genotypes 2 or 3).
The APRICOT is the largest trial conducted so far in co-infected patients assessing the response to current HCV therapy. A total of 289 patients received at least one dose of peg-IFN alpha-2a (Pegasys) 180 μg/week plus a fixed dose of 800 mg ribavirin per day . In contrast with the previous two trials, that study was conducted by the industry (Roche) and included patients from several countries and continents. This was reflected in a lower proportion of patients with HCV genotype 1 (60%) in that trial with respect to the others. The overall rate of sustained virological response was 40%, but dropped to 29% among patients with HCV genotype 1. A close monitoring of patients and strict inclusion criteria provided a relatively low discontinuation rate in that trial (25%), whereas in the French RIBAVIC study up to 36% of patients did not complete therapyapy .
The reasons for the poorest response in HCV/HIV-co-infected patients with respect to HCV-monoinfected individuals are many, and have already been discussed in more detail in the HIV–HCV consensus guidelines . Clearly, new treatment schedules and hopefully new drugs should be investigated to improve the response rates in co-infected patients.
1. Soriano V, Puoti M, Sulkowski M, Mauss S, Cacoub P, Cargnel A, et al. Care of patients with hepatitis C and HIV-coinfection. Updated recommendations from the HCV–HIV International Panel. AIDS 2004; 18:1–12.
2. Perronne C, Carrat F, Bani-Sadr F, Pol S, Rosenthal E, Lunel F, et al. Final results of ANRS HCO2-Ribavic: a randomized controlled trial of pegylated interferon-α 2b + ribavirin versus interferon-α 2b + ribavirin for the initial treatment of chronic hepatitis C in HIV-coinfected patients. In: 11th Conference on Retroviruses and Opportunistic Infections. San Francisco, 2004 [Abstract 117LB].
3. Cargnel A, Angeli E, Mainini A, Gubertini G, Giorgi R, Orlando G, et al. Pegylated interferon alpha-2b plus ribavirin versus pegylated interferon alpha-2b for chronic hepatitis C in HIV+ patients. In: Program and Abstracts of the Digestive Disease Week. Orlando, FL, 17–22 May 2003 [Abstract T1206].
4. Torriani F, Rockstroh J, Rodriguez-Torres M, Lisen E, Gonzalez J, Lazzarin A, et al. Final results of APRICOT: a randomized partially blinded international trial evaluating peg-interferon-α 2a + ribavirin versus interferon-α 2a + ribavirin in the treatment of HCV in HIV/HCV-coinfection. In: 11th Conference on Retroviruses and Opportunistic Infections. San Francisco, 2004 [Abstract 112].
5. Chung R, Andersen J, Volberding P, Robbins G, Liu T, Sherman K, et al. A randomized controlled trial of peg-interferon-α 2a + ribavirin versus interferon-α 2a + ribavirin for chronic hepatitis C virus infection in HIV-coinfected persons: follow-up results of ACTG A5071. In: 11th Conference on Retroviruses and Opportunistic Infections. San Francisco, 2004 [Abstract 110].
© 2004 Lippincott Williams & Wilkins, Inc.