versão On-line ISSN 1678-9199
J. Venom. Anim. Toxins incl. Trop. Dis vol.18 no.1 Botucatu 2012
Specialized Clinic and Day Hospital Domingos Alves Meira, Botucatu Medical School, São Paulo State University (UNESP - Univ Estadual Paulista), Botucatu, São Paulo State, Brazil
The infection by the hepatitis C virus (HCV) remains a major public health problem worldwide, with about 170 million people chronically infected, 3 to 4 million new cases and more than 350 thousands of deaths each year (1). The scientific effort to improve the effectiveness of the treatment gradually increased the chance of cure for chronic hepatitis C (mainly for genotype 1, the most prevalent virus in the Western Hemisphere), which was increased from only 8% when interferon-α started to be used in the 1980s, to almost 50% using pegylated-interferon plus ribavirin, the most up-to-date therapy used in recent years. Nevertheless, the success rate was no better than that of the outcome of a coin toss, and a large number of patients that did not achieved sustained virological response (SVR, effectively representing a cure) is found in clinics with no effective treatment option.
In view of this critical situation, a new class of drugs was created, the HCV protease inhibitors, and in 2011 two molecules were approved for clinical use: boceprevir and telaprevir. These drugs interfere with the HCV replication ability by inhibiting the viral enzyme NS3/4A serine protease, and only work for HCV genotype 1 (2). It is the beginning of a new era in the hepatitis C treatment: the direct-acting antiviral (DAA) therapy.
Both molecules, in the phase 3 studies, had pegylated-interferon plus ribavirin as backbone, adding the new drug to the standard therapy. For naÏve patients, boceprevir increased the rate of success from 38% to 63-66%, and telaprevir from 44% to 69-75% (3, 4). Additionally, the results were more encouraging for those that needed the most, the unsuccessful therapy group. In previously treated patients, boceprevir augmented SVR from 21% to 66%, and telaprevir from 17% from 64% (5-7). These studies used pegylated-interferon plus ribavirin as control group, but the trials and the populations were not the same, so the results could not reflect the difference between the drugs.
These are better days, but new challenges come fast. The DAA therapy increased the adverse effects related to the standard therapy, mainly anemia with boceprevir, and rash with telaprevir. The emergence of resistance mutations and, consequently, treatment failure are a real threat as we learned with HIV therapy. High technology drugs are extremely expensive, so how to render them accessible to patients that require such therapy? Moreover, almost one third of the patients still will not be able to achieve SVR, how do we deal with this group? Again, history repeats itself: preliminary results of new DAA drugs plus standard therapy showed 90% of SVR in null-response patients (8). Place your bets!
1. World Health Organization (WHO). Hepatitis C. Fact Sheet n. 164. June 2011 [cited 2012 Feb 1]. Available from: http://www.who.int/mediacentre/factsheets/fs164/en/. [ Links ]
2. Poordad F. Big changes are coming in hepatitis C. Curr Gastroenterol Rep. 2011;13(1):72-7. [ Links ]
3. Poordad F, McCone J Jr, Bacon BR, Savino B, Manns MP, Sulkowski MS, et al. for the SPRINT-2 Investigators. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011;364(13):1195-206. [ Links ]
4. Jacobson IM, McHutchison JG, Dusheiko G, Di Bisceglie AM, Reddy KR, Bzowej NH, et al. for the ADVANCE Study Team. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med. 2011;364(25):2405-16. [ Links ]
5. Bacon BR, Gordon SC, Lawitz E, Marcellin P, Vierling JM, Zeuzem S et al. for the HCV RESPOND-2 Investigators. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med. 2011;364(13):1207-17. [ Links ]
6. Sherman KE, Flamm SL, Afdhal NH, Nelson DR, Sulkowski MS, Everson GT et al. for The Illuminate Study Team. Response-guided telaprevir combination treatment for hepatitis C virus infection. N Engl J Med. 2011;365(11):1014-24. [ Links ]
7. Zeuzem S, Andreone P, Pol S, Lawitz E, Diago M, Roberts S. for the REALIZE Study Team. Telaprevir for retreatment of HCV infection. N Engl J Med. 2011;364(25):2417-28. [ Links ]
8. Lok AS, Gardiner DF, Lawitz E, Martorell C, Everson GT, Ghalib R, et al. Preliminary study of two antiviral agents for hepatitis C genotype 1. N Engl J Med. 2012; 366(3): 216-224. [ Links ]
Alexandre Naime Barbosa
SAE e Hospital Dia "Domingos Alves Meira"
Departamento de Doenças Tropicais
Faculdade de Medicina de Botucatu
Botucatu, SP, Brasil.
Phone: +55 14 3811 6537.
Received: February 8, 2012.
Accepted: February 8, 2012.
Full paper published online: February 28, 2012.
Conflicts of interest
The author declares that he has received honoraria for serving on advisory boards and giving lectures, including services on speakers bureaus, and travel assistance for conference attendance from Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Merck and Roche in the last year.