Hepatic Safety of Currently Used Antiretroviral Regimens in HIV-infected Patients With Chronic Hepatitis B and/or Hepatitis C Under Real Life Conditions: The HEPAVIR HEPATIC SAFETY Cohort.
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 192
- Locations
- 1
- Primary Endpoint
- Incidence of grade 3 or 4 transaminase elevations
Study Overview
Brief Summary
The purpose of this study is to compare the liver toxicity in HIV-infected patients with chronic hepatitis B and/or hepatitis C, who start a new antiretroviral drug regimen, as well as the influence of the degree of pre-existing liver fibrosis on the incidence of liver toxicity.
Detailed Description
In the last years, various clinical trials and studies have evaluated the incidence of hepatic toxicity (HT) associated with the commonly used antiretroviral drugs in the HIV/hepatitis C virus (HCV)-infected population. Unfortunately, clinical trials that compared hepatic safety of these antiretrovirals include a low number of coinfected patients (van Leth 2004, Molina 2010, Ortiz 2008, Rockstroh 2012). According to recent cohort studies, rates of grade 3 or 4 transaminase elevations (TE) observed in patients receiving ritonavir-boosted protease inhibitors PI/r as lopinavir (LPV/r), atazanavir (ATV/r), fosamprenavir (FPV/r) and darunavir (DRV/r) are similar to those observed in individuals that receive efavirenz (EFV) or raltegravir (RAL) (Pineda 2008, Palacios 2006, Macías 2011, Neukam 2011). However, this conclusion may not be exact due to methodological problems. In this context, currently available data on severe TE are derived from cohort studies that were conducted in different populations, with distinct methods and/or data that was collected retrospectively.
Little information is available on whether the stage of liver damage influences the incidence of HT caused by antiretroviral drugs. Although two studies found an association between advanced fibrosis and higher rates of TE (Aranzabal 2005, Mira 2006), data obtained by further studies are contradictory (Pineda 2008, Palacios 2006, Macías 2011, Neukam 2011) and there are still open questions. Thus, the number of cirrhotic patients is considerably small in these cohorts, however, cirrhosis represents an important comorbidity in HIV. In these individuals, plasmatic concentrations of antiretroviral drugs could reach toxic levels which would be reflected in TE (Barreiro 2007).
Therefore, studies conducted in the same population and with the same methodology are required in order to obtain precise and reliable information on hepatic safety of all commonly used antiretroviral drugs in the clinical practice. These findings could contribute to a better understanding of differences between antiretrovirals and could therefore improve the individualization of antiretroviral therapy in individuals with chronic hepatitis B and/or C. Therefore, the HEPAVIR group of the Andalusian Society of Infectious Diseases (SAEI) has established a prospective cohort: The HEPAVIR Cohort.
Hypothesis: The incidence of severe TE associated with antiretroviral therapy in the clinical practice in hepatitis B virus and/or hepatitis C virus-coinfected patients could be different according to the administered drug.
Primary objective: To determine the incidence of grade 3 or 4 TE associated with antiretroviral therapy in the clinical practice in patients with viral hepatitis.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Older than 18 years
- •HIV-1 infection as confirmed by ELISA and western blot
- •Chronic HCV infection as confirmed by HCV antibodies in plasma, as well as a positive HCV viral load determined by polymerase chain reaction OR chronic hepatitis B infection as confirmed by HBsAg
- •Treatment-naive or pretreated patients who start a new antiretroviral regimen that includes at least one drug that has not been received by the patient before
- •At least one week of exposure to new regimen
- •Liver biopsy or transient elastometry determination within 12 months prior to treatment initiation
Exclusion Criteria
- •Pregnancy
- •Treatment against hepatitis C virus infection
- •Presence of opportunistic infections, including tuberculosis, neoplasia, autoimmune diseases. Patients receiving primary or secondary chemotherapy against an opportunistic process are not included.
- •Any liver disease of vascular, metabolic, biliary, autoimmune or tumoral origin
- •Patients who are not able to provide written informed consent to participate in the study
- •Lack of scheduled clinical visits including blood analysis throughout study period
Arms & Interventions
Antiretroviral drugs
Pre-treated or treatment-naive HIV-infected patients with chronic hepatitis B and/or chronic hepatitis C who change an existing antiretroviral regimen or who start a new regimen.
Intervention: antiretroviral drugs (Drug)
Outcomes
Primary Outcomes
Incidence of grade 3 or 4 transaminase elevations
Time Frame: one year
Secondary Outcomes
- Percentage of patients with undetectable HIV RNA at the end of follow-up(one year)
- CD4 cell count at the end of follow-up(one year)
- Incidence of grade 3 or 4 bilirubin elevations(one year)
Investigators
Karin Neukam
PhD
Valme University Hospital