The purpose of this study is to evaluate if the combination of Lpv/r monotherapy and anti-HCV drugs does not match with additional toxicity induced by the association of HAART and Peg-IFN + ritonavir in HIV/HCV coinfected patients.

Secondary objective is to assess if Lpv/r monotherapy during HCV-treatment is associated with HIV efficacy versus optimized HAART.

This is a pilot, randomised, open label, controlled clinical trial. All eligible patients(CD4>350, HIV RNA<50 copies and no PI mutations) will be randomized (1:1) to receive LPV/r new tabs (200/50 mg, 2 cpr BID) monotherapy (arm A) or LPV/r + selected NUCS (arm B) associated to anti-HCV therapy for 12 months. The number of subjects to recruit, in each arm of the study, is equal to 25, the total number of subjects to enrol will be 50.

• Group A: will receive LPV/r monotherapy and anti HCV drugs for 12 months.
• Group B: will receive LPV/r+ selected NUCS and anti HCV drugs for 12 months. All the patients will be followed-up for six months after the end of anti-HCV drugs for the evaluation of Sustained Virological Response (SVR). At the end of the co-treatment for HCV/HIV, each subject will be treated for HIV infection according to physician decisions.As anti-HCV drugs the patients will receive PEG-IFNa 2a 180 mcg/week + Ribavirin 1-1.2 g/day .At the end of the third month of combined therapy, only patients who reach an early virological response will continue anti-HCV drugs.

Inclusion Criteria:

• Subject is >18 years old
• Subject has given written informed consent
• Subject has a confirmed diagnosis of HIV and HCV infection
• Subject is naive for HCV-infection treatment
• Subject has chronic hepatitis and/or subject has compensated cirrhosis (Child class A)
• Subject has a CD4+ count of > 350 cell/mmc
• Subject is HIV-RNA negative during the previous six month
• Subject is on stable HAART including r/LPV for > 6 months
• Subject has genotype available at baseline and no mutations associated with resistance to PI or no virologic failure on PI treatment, defined as a confirmed HIV-RNA level>50 cp/mL after 24 weeks, > 50 cp/ml after 48 weeks, or a repeated HIV RNA level > 50 cp/mL after prior suppression of viremia to< 50 cps/mL.
• Free of any clinically significant disease (other than HIV and HCV) that would interfere with study evaluations.
• Subject will use effective contraceptive methods for the duration of the study

Exclusion Criteria:

• Subject is HbsAg positive
• Subject has cirrhosis score Child-Pugh B/C,
• No previous hepatic decompensation
• Subject has HIV-related thrombocytopenia (Platelets count < 50.000/mmc)
• Subject has neutrophils count < 1500/mmc
• Subject has Hb value < 11 g/dL
• Subject has creatinine value > 1.5 mg/dL
• Subject is pregnant or wishes to become so
• Subject has any cause of liver disease other than chronic hepatitis C, status of liver decompensation or any other condition consistent with decompensated liver disease (bleeding from esophageal varices, signs of current bleeding, significant ascites, hepatic encephalopathy)
• Subject is alcohol abuser (> 30 gr/die)
• Subject has autoimmune hepatitis
• Prior treatment with PEG-IFN or ribavirin
• Illicit drugs abuse that in the opinion of the investigator could lead to poor compliance with the terms of the protocol (Methadone sostitution therapy allowed)
• Active heart disease (e.g. angina, congestive heart failure, recent myocardial infarction or significant arrhythmia)
• Subject has pre-existing severe depression, condition of severe psychiatric disorders such as suicidal ideation, suicide attempts, depression or acute psychosis
• Subject has uncompensated diabetes
• Subject has active opportunistic infections or major opportunistic infections during the previous 12 months
• Subject has known hypersensitivity or contraindication to study medications
• Subject has any other condition that in the opinion of the investigator will make the subject unsuitable for enrolment or will interfere with the subject participating in or completing the study