Treatment of HIV/HCV Coinfection With Peg-IFN and Ribavirin in Patients Receiving ART Monotherapy With Lopinavir/r (PEKARI)
The aim of this study is to assess the efficacy of lopinavir/r in monotherapy and peg-interferon plus ribavirin for the control of both HIV and HCV infection respectively after 12 months of active treatment for HCV.
Drug: Lopinavir/ritonavir with two nucleoside analogs
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Multicenter, Randomized, Open Label, Pilot Study to Assess the Possibility of Concomitant Treatment of HCV/HIV co Infection With Peg-interferon + Ribavirin, and Lopinavir/r as a Single Antiretroviral Agent.|
- Assess efficacy of concomitant treatment with lopinavir/r monotherapy and PEG-INF plus RBV for the control of both HIV and HCV infection respectively after 12 months of active treatment for HCV [ Time Frame: 80 weeks ] [ Designated as safety issue: Yes ]
- Tolerability and safety of concomitant treatment with LPV/r, PEG-INF and RBV [ Time Frame: 80 weeks ] [ Designated as safety issue: Yes ]
- CD4 [ Time Frame: 80 weeks ] [ Designated as safety issue: Yes ]
- Efficacy [ Time Frame: 80 weeks ] [ Designated as safety issue: Yes ]
- Adherence [ Time Frame: 80 weeks ] [ Designated as safety issue: Yes ]
|Study Start Date:||February 2008|
|Study Completion Date:||October 2012|
|Primary Completion Date:||June 2012 (Final data collection date for primary outcome measure)|
Lopinavir/ritonavir (LPV/r) as single antiretroviral administered concomitantly with peg-interferon and ribavirin
Other Name: Kaletra
Active Comparator: 2
Lopinavir/ritonavir (LPV/r) with 2 NRTIs, administered concomitantly with peg-interferon and ribavirin
Drug: Lopinavir/ritonavir with two nucleoside analogs
LPV/r plus 2NRTIs + PEG-INF + RBV
Viral hepatitis, mainly when caused by the hepatitis C virus (HCV), is highly significant in the setting of infection by the human immunodeficiency virus (HIV) because high activity antiretroviral therapy (HAART) has a very favorable impact upon morbidity and mortality of this disease. HAART has achieved disease control, significantly increasing survival and improving the quality of life of subjects with HIV infection.
Spain has one of the highest prevalences of HIV-HCV co-infection because both HCV and HIV infection are strongly associated to being or having been an intravenous drug user (IDU); thus, from 61% to 69% of these subjects infected by HIV in Spain are also infected by HCV.
From 1998, standard treatment for chronic C hepatitis consists of the combination of interferon alpha and ribavirin, based on an increased efficacy versus interferon monotherapy; however, development of pegylated interferon, with a more convenient bioavailability as compared to conventional interferon alpha, has allowed for developing even more effective combined therapies and the possibility of improving response prediction based on changes in viremia within the first few weeks of treatment. However, treatment of HCV infection usually involves severe side effects, which often lead to treatment discontinuation or to the need for adjusting drug dosage, in which case treatment efficacy may decrease.
HCV+ subjects who, because of HIV co-infection, should also receive HAART, may have an increased number or increased severity of adverse reactions due to interactions occurring with drug co-administration.
Lopinavir/ritonavir (LPV/r) is a potent HIV protease inhibitor and is characterized by a very high pharmacological and genetic barrier.
Different studies (subject cohorts, uncontrolled studies) during the past years have appeared in the literature showing the efficacy of LPV/r or controlling viral replication.
Most studies were conducted with the soft gel capsule formulation of LPV/r. In this study, the new formulation of LPV/r (Kaletra) as tablets approved by the FDA and EMEA (Spain authorization 30th Oct 2006) will be used. This new formulation will provide additional benefits to this strategy that has only been studied to date with soft gel capsules.
Based on the foregoing and on the additional cost savings involved in this strategy, we think that LPV/r, as single antiretroviral agent concomitantly administered with treatment for hepatitis C virus infection may provide significant benefits because it would prevent interactions between NRTIs and ribavirin, thus being potentially able to decrease the adverse events derived from mitochondrial toxicity and minimizing the possibility of anemia. In addition, replacement of NNRTIs by LPV/r may significantly decrease CNS involvement that may be enhanced by co-administration of efavirenz and peg-interferon, or minimize the risk of hepatotoxicity caused by nevirapine.
|Hospital Germans Trias i Pujol|
|Badalona, Barcelona, Spain, 08910|
|San Sebastian, Guipuzcoa, Spain|
|Hospital General Sta. Mª del Rosell|
|Cartagena, Murcia, Spain, 30203|
|Hospital General de Castellón|
|Castellón, Spain, 12004|
|Hospital La Princesa|
|Hospital Ramón y Cajal|
|Madrid, Spain, 28034|
|Hospital Gregorio Marañón|
|Madrid, Spain, 28007|
|Hospital la Paz|
|Madrid, Spain, 28046|
|Hospital General Universitario de Valencia|
|Valencia, Spain, 46014|
|Hospital La Fe|
|Valencia, Spain, 46009|
|Study Chair:||Enrique Ortega||Hospital General de Valencia|