Trial About Hepatic Security of Antiretroviral Treatment Based on Kaletra Versus Nevirapine in co-Infected HIV/HCV Patients
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Prospective, Open Label and Randomized Clinical Trial About Hepatic Security of Antiretroviral Treatment Based on Kaletra Versus Nevirapine in co-Infected HIV/HCV Patients|
- The average of hepatic rigidity increase in each group. Hepatic rigidity will be measured in kilopascals through elastography (Fibroscan). Distribution of hepatic rigidity will be normalized by a logarithmic transformat [ Time Frame: From Basal to 144 week (last visit) every 3 months ] [ Designated as safety issue: Yes ]
- Virological and immunologic efficacy will be assessed through the proportion of patients with virological failure during the follow-up and the CD4 lymphocytes count of both treatment regimens. [ Time Frame: From Basal to 144 week (last visit) every 3 months ] [ Designated as safety issue: No ]
- The effect of both treatments in lipidic and glucidic metabolism will be assessed through the following variables: Total Cholesterol, HDL and LDL Cholesterol, Triglycerides and Glucose. [ Time Frame: From Basal to 144 week (last visit) every 3 months ] [ Designated as safety issue: Yes ]
- Higher than log 7.2 Kpa in patients with non-significant basal fibrosis (less than log 7.2 Kpa) [ Time Frame: From Basal to 144 week (last visit) every 3 months ] [ Designated as safety issue: Yes ]
- The security of each regimen will be studied through the proportion of patients who give up treatment because of adverse events and hepatic-related adverse events presence. [ Time Frame: From Basal to 144 week (last visit) every 3 months ] [ Designated as safety issue: Yes ]
- Toxicity will be determined depending on: Clinical History and Physical Examination; Coagulation, hemogram and chemistry tests, which will include: transaminase levels, GGT, alkaline phosphatase, bilirrubin, albumin, urea and creatinin [ Time Frame: From Basal to 144 week (last visit) every 3 months ] [ Designated as safety issue: Yes ]
- Mortality rate during the study will be evaluated. [ Time Frame: From Basal to 144 week (last visit) every 3 months ] [ Designated as safety issue: Yes ]
|Study Start Date:||February 2008|
|Study Completion Date:||December 2008|
|Primary Completion Date:||December 2008 (Final data collection date for primary outcome measure)|
Active Comparator: 1
2 ITIAN (o 1 ITIAN+TDF)+ nevirapine, 2 tablet 200/50 mg to 12 hours
2 ITIAN (o 1 ITIAN+TDF)+ lopinavir/ritonavir, 2 tablet 200/50 mg to 12 hours
The prevalence of the HIV-HCV co-infection in Spain is one of the highest because both infections are strongly related to parenteral drugs use; so, from 61 to 69 % of HIV infected patients are also HCV infected.
Acute HCV infection is asymptomatic in 60 to 70% of cases, being the chronification the natural illness evolution. 20% of the patients will develop hepatic cirrhosis after 20 to 30 years of being infected by the HCV. In cirrhosis cases, the hepatocellular carcinoma appears in a rate of 2 to 4% per year, according to studies done with HCV mono-infected patients. Fibrosis progression depends basically on the duration of HCV infection and on the age of infection, but also on other factors, like gender (is faster in men), alcohol consumption (worst over 50 g per day) and HIV co-infection. Several epidemiologist studies have described the negative impact of HIV co-infection, accelerating the progression to cirrhosis and the hepatocarcinoma.
The Highly Active Antiretroviral Treatment (HAART) has a positive impact on survival on co-infected patients, although the three drug families used in HAART can cause hepatic toxicity in this group of patients. Hepatic toxicity appears in 5 to 20% of patients, being more serious and common, but not exclusive, in case of NVP treatment.
On their part, not all PI have the same hepatotoxic profile. An association between serious hepatotoxicity and ritonavir at full strength, indinavir and indinavir plus saquinavir boosted with ritonavir has been found.
As far as fibrosis is concerned, there are studies that show that in HIV/HCV co-infected patients PI-based regimens are associated with a lower progression to fibrosis, while the progression rate to cirrhosis is higher in NVP-based regimens, mainly in those patients with advanced hepatic fibrosis.
Hepatic biopsy is considered the reference test to assess hepatic fibrosis, nevertheless it is an invasive, painful and with a low but potentially serious risk for the patient's life. Moreover, the viability of a hepatic biopsy can be doubted due to sampling error or interobservation variability. For that reason, several biochemist tests have been developed to reflect the hepatic fibrosis extent or stage in a reliable way. Recently a hepatic rigidity measure through elastography has been presented as a non-invasive and very promising method to assess hepatic fibrosis.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00661349
|Hospital Son Dureta|
|Palma de Mallorca, Baleares, Spain, 07014|
|H.U. Germans Trias i Pujol - Unitat VIH, Fundació Lluita contra la Sida|
|Badalona, Barcelona, Spain, 08916|
|Hospital General Universitario de Alicante|
|Alicante, Spain, 03010|
|Hospital Clínic i Provincial de Barcelona|
|Barcelona, Spain, 08036|
|Hospital Universitario Príncipe de Asturias|
|Madrid, Spain, 28005|
|Hospital Clínico San Carlos|
|Madrid, Spain, 28040|
|Hospital Universitario la Paz|
|Madrid, Spain, 28046|
|Hospital Clínico de Salamanca|
|Salamanca, Spain, 37007|
|Hospital Universitario de Valme|
|Sevilla, Spain, 41014|