Challenges in the treatment of HIV and HCV coinfection.

HIV and hepatitis C virus (HCV) infections are pandemic illnesses that represent serious global public health problems. It is estimated that there are currently 38 million people infected with HIV and 60-180 million people infected with HCV worldwide. Owing to similar transmission pathways, HIV/HCV coinfection occurs frequently and, indeed, affects approximately a third of all European and North American HIV patients. With the successful introduction of highly active antiretroviral therapy (HAART) for the treatment of HIV in 1996, the morbidity and mortality owing to HIV declined drastically. As the prognosis of HIV infection has improved, liver disease caused by chronic infection with HCV has become increasingly important for mortality and morbidity among HIV/HCV-coinfected patients. Coinfection leads to accelerated progression of liver fibrosis and development of cirrhosis, as well as earlier emergence of hepatocellular carcinomas. Pegylated interferon and ribavirin combination therapy of HCV in coinfected patients showed reasonable sustained virological responses in randomized clinical trials, ranging from 27 to 44%, which, however, is substantially lower than in HCV monoinfected patients. Furthermore, cohort analyses have shown that HAART-induced immune reconstitution can improve the natural course of hepatitis C significantly and delay fibrosis progression. As pharmacokinetic drug-drug interactions and higher rates of hepatotoxicity following HAART initiation must be considered in HIV/HCV coinfection, specific treatment and management guidelines have been developed to optimize care in this clinically challenging group of patients.