Lopinavir/Ritonavir Monotherapy Versus Standard Highly Active Antiretroviral Therapy (HAART) in HIV/HCV Coinfected Antiretroviral (ARV) Naive Patients Starting Treatment With Anti-HCV Therapy

Study Overview
=================
Brief Summary
-----------------
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 patients naive for HIV and HCV. Secondary objective is to assess if Lpv/r monotherapy during HCV-treatment is associated with HIV efficacy vs optimized HAART.

Detailed Description
-----------------
This is a pilot, randomised, open label, controlled clinical trial. All eligible patients (CD4 count > 200 and no PI resistance)will receive 26 weeks induction HAART (LPV/r + selected NUCS). At the end of induction period (Phase I), all subjects with negative HIV-RNA from at least two months, Hb > 11 g/dL and CD4 count > 350 cells/mmc will be randomised (1:1), to receive LPV/r new tabs (200/50 mg, 2 cpr BID) monotherapy (arm A) or to continue the same HAART (arm B), associated to anti-HCV therapy for other 48 weeks (Phase II). The number of subjects to recruit will be 60 subjects to start the induction-phase with the aim to randomize, at least 25 subjects in each arm of the study. The total number of subjects to randomize will be 50. The Group A: will receive LPV/r + selected NRTIs for 26 weeks, followed by LPV/r monotherapy and anti HCV drugs for 48 weeks. Group B: will receive LPV/r+ selected NRTIs for 24 weeks, followed by the same HAART and anti-HCV drugs for 48 weeks. At the end of the co-treatment for HCV/HIV, each subject will be treated for HIV infection according to physician decision.All the patients will be followed-up for 24 weeks after the end of anti-HCV drugs for the evaluation of SVR.As anti-HCV drugs the patients will receive PEG-IFNa 2a 180 mcg/week + Ribavirin 1-1.2 g/day . At the end of week 12 of combined therapy, only patients who will reach an early virological response will continue anti-HCV drugs.

Official Title
-----------------
Pilot, Multicenter, Randomized Study on Lopinavir/Ritonavir-Monotherapy vs Lopinavir/Ritonavir Plus Selected Nucs, in HIV/HCV ARV-Naive Coinfected Patients With Chronic Hepatitis C or Compensated Cirrhosis, Starting Treatment With Ribavirin and Pegylated Interferon

Conditions
-----------------
HIV Infections, Hepatitis C

Intervention / Treatment
-----------------
* Drug: LPV/r
* Drug: Nucleoside Reverse Transcriptase Inhibitors
* Drug: PEG-IFNa 2a
* Drug: Ribavirin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject is >18 years old Subject has given written informed consent Serologic evidence of HIV infection by HIV antibody and HIV-RNA detection Serologic evidence of HCV infection by HCV antibody and HCV-RNA detection Subject is naive for HIV and HCV therapy Subject has active chronic hepatitis or compensated cirrhosis (Child-Pugh class A) Subject has a CD4+ count > 200 cell/mm3 and <500 cell/mm3. Subject has genotype available at baseline and no mutations (IAS)associated with resistance to antiretroviral drugs used. Subject and partner 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 < 9 g/dL at screening and <11 g/dL at randomization Subject has creatinine value > 1.5 mg/dL Subject is on a HAART regimen included ddI and/or AZT 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) Prior treatment with PEG-IFN/ribavirin Illicit drugs abuse that in the opinion of the investigator could lead to poor compliance with the terms of the protocol (maintenance treatment with methadone 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>LPV/r + selected NRTIs for 26 weeks, followed by LPV/r monotherapy and anti HCV drugs for 48 weeks. All the patients will be followed-up for 24 weeks after the end of anti-HCV drugs for the evaluation of SVR.As anti-HCV drugs the patients will receive PEG-IFNa 2a 180 mcg/week + Ribavirin 1-1.2 g/day . At the end of week 12 of combined therapy, only patients who will reach an early virological response will continue anti-HCV drugs. | Drug: LPV/r<br>* Lopinavir/Ritonavir 200/50 mg 2 cpr BID monotherapy - 26 weeks (A) or 24 weeks (B)<br>Drug: Nucleoside Reverse Transcriptase Inhibitors<br>* NRTIs for 26 weeks (A) or 24 weeks (B)<br>Drug: PEG-IFNa 2a<br>* PEG-IFNa 2a 180 mcg/week (48 weeks)<br>Drug: Ribavirin<br>* Ribavirin 1-1.2 g/day (48 weeks)<br>|
| Active Comparator: B<br>LPV/r+ selected NRTIs for 24 weeks, followed by the same HAART and anti-HCV drugs for 48 weeks. At the end of the co-treatment for HCV/HIV, each subject will be treated for HIV infection according to physician decision. All the patients will be followed-up for 24 weeks after the end of anti-HCV drugs for the evaluation of SVR.As anti-HCV drugs the patients will receive PEG-IFNa 2a 180 mcg/week + Ribavirin 1-1.2 g/day . At the end of week 12 of combined therapy, only patients who will reach an early virological response will continue anti-HCV drugs. | Drug: LPV/r<br>* Lopinavir/Ritonavir 200/50 mg 2 cpr BID monotherapy - 26 weeks (A) or 24 weeks (B)<br>Drug: Nucleoside Reverse Transcriptase Inhibitors<br>* NRTIs for 26 weeks (A) or 24 weeks (B)<br>Drug: PEG-IFNa 2a<br>* PEG-IFNa 2a 180 mcg/week (48 weeks)<br>Drug: Ribavirin<br>* Ribavirin 1-1.2 g/day (48 weeks)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess if the combination of LPV/r monotherapy in association with |  | 18 months | 
| anti-HCV therapy (PEG IFN alfa 2a + Ribavirin) does not match with additional |  | 18 months | 
| toxicity induced by the combination of optimized HAART (Lopinavir/ritonavir + selected Nucs) and PEG-IFN alfa 2a+Ribavirin |  | 18 months | 
| in patients naïve for HIV and HCV |  | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess if LPV/r monotherapy during the HCV treatment |  | 18 and 24 months | 
| is associated with anti HIV efficacy and a better patient satisfaction |  | 18 and 24 months | 
| vs optimized HAART. |  | 18 and 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HIV/HCV, HIV and HCV coinfected patients, Treatment Naive