Hepatitis C: Situación y manejo actuales, nuevos medicamentos

Hepatitis C/HIV Coinfection


Douglas G. Fish, M.D.,  Albany Medical College, Albany, N.Y., EE.UU.


Hepatitis C is an RNA virus that affects many with HIV infection, particularly those whose risk factor is injection drug use.  In numerous studies, as many as 90% of patients whose HIV risk factor is injection drug use are coinfected with hepatitis C.  Even among HIV-infected men who have sex with men in the U.S., the prevalence of hepatitis C is higher than among the general population.  This points to the potential for sexual transmission of hepatitis C, especially among those with multiple partners, with resulting genital tract inflammation that may facilitate HCV transmission.  It is recommended that all persons with HIV infection be tested for hepatitis C.


Of those infected with hepatitis C, 20-30% appear to spontaneously clear their infection, while the remaining go on to have chronic disease.  Younger age and female sex favor viral clearance.  Of those chronically infected, approximately 20% will go on to develop cirrhosis, and of these, 20% will go on to develop hepatocellular carcinoma.  Those with HCV/HIV coinfection have more rapidly progressive fibrosis and ultimate cirrhosis than those with HCV infection alone.  Other risk factors for progression of hepatitis C include male sex, age > 40 years, alcohol use, iron overload and chronic hepatitis B infection.


The goal of hepatitis C treatment is cure.  Unlike HIV, HCV RNA is not integrated into the host genetic material, and so is potentially curable.  Genotypes 2 & 3 are easier to treat, and genotypes 1 & 4 more difficult, the latter requiring one year of treatment for sustained virological responses.


Studies of HCV/HIV coinfected patients will be presented.  As with the mono-HCV-infected patients, coinfected patients have responded best, albeit less, to combination therapy with pegylated interferon and ribavirin.  The exception to this is those patients with genotypes 2 or 3, who seem to respond nearly as well to standard interferon with ribavirin.  Pegylated interferon has the advantage of a sustained therapeutic drug concentration over a one week period.  Sustained response rates of 35-45% have been seen among coinfected patients with pegylated interferon and ribavirin, with slightly better results for those with genotyopes 2 or 3, and slightly worse results for those with genotypes 1 or 4.  Side effects are similar betweenstandard and pegylated interferon, though some of the hematological toxicities might be slightly higher with the pegylated formulation.  Anxiety and depression are relatively common side effects of interferon, and patients should be observed closely for development of these symptoms.  Suicides have been reported on and shortly after discontinuation of interferon therapy.  For patients with a history of anxiety or depression that is currently stable, many experts recommend psychiatric consultation and pretreatment with an antidepressant.


Anemia is an expected complication of hepatitis C therapy, and occurs as a result of bone marrow suppression from the interferon and hemolysis from the ribavirin.  HAART that includes azidothymidine (AZT) may need to be revised to exclude AZT while on hepatitis C treatment as a result.  Exogenously administered erythropoietin can help maintain or restore hemoglobin in patients receiving HCV treatment.  Other drug interactions between HCV treatment and HAART may occur, most notably increased didanosine (DDI) levels when combined with ribavirin, with the potential risk for pancreatitis.


In summary, enormous progress has been made in the treatment of hepatitis C, and our coinfected patients are increasingly benefiting from these advances.  Prevention opportunities also exist with vaccination of susceptible individuals with chronic hepatitis C against hepatitis A and hepatitis B.