Hepatic Safety of Currently Used Antiretroviral Regimens in Patients With Chronic Hepatitis Under Real Life Conditions

NCT01908660 | Completed

• 1 other identifier: SEG-HEP-2007
• Study Type: observational
• Target: 192
• Locations: 1 country
• Sites: 1

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.

Conditions

Human Immunodeficiency Virus; Hepatitis B, Chronic; Hepatitis C, Chronic

Keywords

HIV; hepatitis C virus; hepatitis B virus; antiretroviral drugs; nucleos(t)ide reverse transcriptase inhibitors; non-nucleos(t)ide reverse transcriptase inhibitors; protease inhibitors; integrase inhibitors; entry inhibitors; transaminase elevations; alanine aminotransferase; aspartate aminotransferase; bilirubin elevations; hepatic fibrosis

Outcome Measures

Primary Outcomes (1)

• Incidence of grade 3 or 4 transaminase elevations

  one year

Secondary Outcomes (3)

• Incidence of grade 3 or 4 bilirubin elevations

  one year

• 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

Study Arms (1)

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.

Drug: antiretroviral drugs

Interventions

antiretroviral drugs DRUG

zidovudine lamivudine emtricitabine abacavir tenofovir nevirapine efavirenz etravirine rilpivirine lopinavir atazanavir fosamprenavir darunavir raltegravir maraviroc ritonavir

Antiretroviral drugs

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients seen at the infectious disease unit of a terciary care center

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Valme University Hospital: lead
• Hospital Universitario Virgen de la Victoria: collaborator
• Hospital Universitario Reina Sofia de Cordoba: collaborator
• Hospital Torrecárdenas: collaborator
• Hospital de la Línea de la Concepción: collaborator
• Hospital Poniente: collaborator
• Hospital Universitario Virgen Macarena: collaborator
• Complejo Hospitalario de Especialidades Juan Ramón Jimenez: collaborator

Study Sites (1)

Hospital Universitario de Valme

Seville, 41014, Spain

Location

Related Publications (10)

• van Leth F, Phanuphak P, Ruxrungtham K, Baraldi E, Miller S, Gazzard B, Cahn P, Lalloo UG, van der Westhuizen IP, Malan DR, Johnson MA, Santos BR, Mulcahy F, Wood R, Levi GC, Reboredo G, Squires K, Cassetti I, Petit D, Raffi F, Katlama C, Murphy RL, Horban A, Dam JP, Hassink E, van Leeuwen R, Robinson P, Wit FW, Lange JM; 2NN Study team. Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN Study. Lancet. 2004 Apr 17;363(9417):1253-63. doi: 10.1016/S0140-6736(04)15997-7.

  PMID: 15094269 BACKGROUND

• Molina JM, Andrade-Villanueva J, Echevarria J, Chetchotisakd P, Corral J, David N, Moyle G, Mancini M, Percival L, Yang R, Wirtz V, Lataillade M, Absalon J, McGrath D; CASTLE Study Team. Once-daily atazanavir/ritonavir compared with twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 96-week efficacy and safety results of the CASTLE study. J Acquir Immune Defic Syndr. 2010 Mar;53(3):323-32. doi: 10.1097/QAI.0b013e3181c990bf.

  PMID: 20032785 BACKGROUND

• Ortiz R, Dejesus E, Khanlou H, Voronin E, van Lunzen J, Andrade-Villanueva J, Fourie J, De Meyer S, De Pauw M, Lefebvre E, Vangeneugden T, Spinosa-Guzman S. Efficacy and safety of once-daily darunavir/ritonavir versus lopinavir/ritonavir in treatment-naive HIV-1-infected patients at week 48. AIDS. 2008 Jul 31;22(12):1389-97. doi: 10.1097/QAD.0b013e32830285fb.

  PMID: 18614861 BACKGROUND

• Rockstroh J, Teppler H, Zhao J, Sklar P, Harvey C, Strohmaier K, Leavitt R, Nguyen BY. Safety and efficacy of raltegravir in patients with HIV-1 and hepatitis B and/or C virus coinfection. HIV Med. 2012 Feb;13(2):127-31. doi: 10.1111/j.1468-1293.2011.00933.x. Epub 2011 May 22.

  PMID: 21599819 BACKGROUND

• Pineda JA, Santos J, Rivero A, Abdel-Kader L, Palacios R, Camacho A, Lozano F, Macias J; Liverey Study Investigator Team. Liver toxicity of antiretroviral combinations including atazanavir/ritonavir in patients co-infected with HIV and hepatitis viruses: impact of pre-existing liver fibrosis. J Antimicrob Chemother. 2008 Apr;61(4):925-32. doi: 10.1093/jac/dkn045. Epub 2008 Feb 14.

  PMID: 18276600 BACKGROUND

• Palacios R, Vergara S, Rivero A, Aguilar I, Macias J, Camacho A, Lozano F, Garcia-Lazaro M, Pineda JA, Torre-Cisneros J, Marquez M, Santos J. Low incidence of severe liver events in HIV patients with and without hepatitis C or B coinfection receiving lopinavir/ritonavir. HIV Clin Trials. 2006 Nov-Dec;7(6):319-23. doi: 10.1310/hct0706-319.

  PMID: 17197379 BACKGROUND

• Macias J, Neukam K, Portilla J, Iribarren JA, de Los Santos I, Rivero A, Marquez M, Delgado M, Tellez F, Merino D, Giner L, von Wichmann MA, Pineda JA; HEPRAL study team. Liver tolerance of raltegravir-containing antiretroviral therapy in HIV-infected patients with chronic hepatitis C. J Antimicrob Chemother. 2011 Jun;66(6):1346-50. doi: 10.1093/jac/dkr083. Epub 2011 Mar 10.

  PMID: 21398295 BACKGROUND

• Aranzabal L, Casado JL, Moya J, Quereda C, Diz S, Moreno A, Moreno L, Antela A, Perez-Elias MJ, Dronda F, Marin A, Hernandez-Ranz F, Moreno A, Moreno S. Influence of liver fibrosis on highly active antiretroviral therapy-associated hepatotoxicity in patients with HIV and hepatitis C virus coinfection. Clin Infect Dis. 2005 Feb 15;40(4):588-93. doi: 10.1086/427216. Epub 2005 Jan 21.

  PMID: 15712082 BACKGROUND

• Barreiro P, Rodriguez-Novoa S, Labarga P, Ruiz A, Jimenez-Nacher I, Martin-Carbonero L, Gonzalez-Lahoz J, Soriano V. Influence of liver fibrosis stage on plasma levels of antiretroviral drugs in HIV-infected patients with chronic hepatitis C. J Infect Dis. 2007 Apr 1;195(7):973-9. doi: 10.1086/512086. Epub 2007 Feb 20.

  PMID: 17330787 BACKGROUND

• Neukam K, Mira JA, Ruiz-Morales J, Rivero A, Collado A, Torres-Cornejo A, Merino D, de Los Santos-Gil I, Macias J, Gonzalez-Serrano M, Camacho A, Parra-Garcia G, Pineda JA; SEGURIDAD HEPATICA Study Team of the Grupo HEPAVIR de la Sociedad Andaluza de Enfermedades Infecciosas (SAEI). Liver toxicity associated with antiretroviral therapy including efavirenz or ritonavir-boosted protease inhibitors in a cohort of HIV/hepatitis C virus co-infected patients. J Antimicrob Chemother. 2011 Nov;66(11):2605-14. doi: 10.1093/jac/dkr357. Epub 2011 Sep 7.

  PMID: 21903660 RESULT

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Hepatitis B, Chronic; Hepatitis C, Chronic; Hepatitis C; Hepatitis B; Liver Cirrhosis

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Flaviviridae Infections; Fibrosis

Study Officials

• Karin I Neukam, PhD

  Hospital Universitario de Valme

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Year
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD

Study Record Dates

• First Submitted: June 28, 2013
• First Posted: July 26, 2013
• Study Start: January 1, 2007
• Primary Completion: September 1, 2015
• Study Completion: October 1, 2015
• Last Updated: November 11, 2015

Record last verified: 2015-11

Locations

ES (1)