AIDS Reviews 2007;9 1 Treating Hepatitis C Virus in HIV Patients: Are Side Effects a Real Obstacle? Francesca Gatti, Paola Nasta, Alessandro Matti, Daniela Manno, Monia Mendeni, Massimo Puoti and Giampiero Carosi Department of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy Abstract Hepatitis C virus-related long-term complications are nowadays a leading cause of morbidity and mortality in HIV-infected persons. According to international guidelines, all HIV/HCV-coinfected pa- tients should be evaluated and, if eligible, treated with pegylated interferon plus ribavirin. The man- agement of anti-HCV treatment side effects, which may be even more serious in HIV patients, is very important to minimize treatment early discontinuations. The purpose of this review is to supply clini- cians with an update, provided by the most recent and relevant literature, of underlying mechanisms, incidence, and advice about the management of pegylated interferon and ribavirin side effects in HCV/HIV-coinfected patients. (AIDS Reviews 2007;9:1-2) Corresponding author: Francesca Gatti, francesca_gatti1@virgilio.it Key words HCV/HIV coinfection. Interferon. Ribavirin. Side effects. AIDS Reviews 2007;9:16-24 Correspondence to: Francesca Gatti Clinica di Malattie Infettive e Tropicali AO Spedali Civili p.zzle Spedali Civili 1 25123 Brescia, Italy E-mail: francesca_gatti1@virgilio.it Introduction Chronic hepatitis C virus (HCV)-related liver disease is an important cause of comorbidity for HIV-infected patients. Coinfection with HCV and HIV is highly fre- quent, in particular among subjects at risk of parenteral transmission (hemophiliacs, ex-drug addicts), with a percentage of up to 90-100% according to case histo- ries 1-3 . Moreover, complications of end-stage liver dis- ease (ESLD) are currently one of the main causes of morbidity and mortality among coinfected subjects on HAART, as incidence and mortality due to opportunis- tic HIV-related diseases is dramatically reduced 4-8 . It has been suggested that the deficiency of cell-medi- ated immune response characterizing HIV infection actually favors the chronic development of acute HCV infection 9 and also the progression of chronic hepatitis to cirrhosis 10 . For these reasons, the published guide- lines considering all coinfected patients as potential candidates for treatment with interferon (IFN) and riba- virin have gained unanimous consensus 11-13 . These recommendations are supported by recently published, randomized, controlled clinical trials showing the effi- cacy of combination treatment with pegylated inter- feron (PEG-IFN) and ribavirin in coinfected subjects, and its superiority over recombinant IFN and PEG-IFN monotherapies or recombinant IFN/ribavirin combina- tion (Table 1). Nevertheless, the management of this treatment is often made difficult by numerous side ef- fects, which frequently lead to treatment interruption or dose reduction that cause the exposure of patients to suboptimal doses of one or both of the drugs and compromise the potential efficacy of the treatment 14,15 . The greater incidence and seriousness of such unde- sirable effects in coinfected patients is often cited as a cause of reduced adherence and consequently as one of the principal factors of reduced efficacy of anti- HCV treatment in this particular population 16 . The aim of this review is to compare the incidence of side effects of anti-HCV treatment among mono- and coinfected subjects, with reference to the main ran-