Hepatic Safety of Raltegravir Versus Efavirenz as HIV Therapy for Patients With HIV and HCV Coinfection

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified September 2013 by University of Hawaii
Sponsor:
Collaborators:
Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
Viet Tiep General Hospital, Hai Phong, Vietnam
Oxford University Clinical Research Unit, Vietnam
Information provided by (Responsible Party):
University of Hawaii
ClinicalTrials.gov Identifier:
NCT01147107
First received: June 16, 2010
Last updated: October 30, 2013
Last verified: September 2013

June 16, 2010
October 30, 2013
December 2013
December 2016   (final data collection date for primary outcome measure)
Rates of Grade 2 and higher alanine aminotransferase (ALT) elevations [ Time Frame: over week 72 ] [ Designated as safety issue: Yes ]
To estimate the rates of grade 2*and higher ALT elevations in the two regimens.
  • Plasma HIV RNA </= 50 copies/mL [ Time Frame: 24 and 72 weeks ] [ Designated as safety issue: No ]
    The rates of HIV virologic suppression (plasma HIV RNA < 50 copies/mL) at week 24 and 72 of study in the two arms of the study will be estimated.
  • Grade 2 and higher alanine aminotransferase (ALT) elevations [ Time Frame: over week 72 ] [ Designated as safety issue: Yes ]

    To estimate the rates of grade 2*and higher ALT elevations in the two regimens.

    * grade 2 = ALT elevations 2.6-5.0 x upper limit of normal [ULN]; grade 3 = ALT 5.1-10.0 x ULN; grade 4 = >10.0 x ULN

Complete list of historical versions of study NCT01147107 on ClinicalTrials.gov Archive Site
  • Plasma HIV RNA </= 150 copies/mL by the Abbot M2000 platform [ Time Frame: 24 weeks and 72 weeks ] [ Designated as safety issue: Yes ]
    To estimate rates of HIV virologic suppression at week 24 and week 72
  • Change in CD4 count [ Time Frame: from entry to week 24, from entry to week 72 ] [ Designated as safety issue: Yes ]
    To assess changes in CD4 counts from entry to week 24 and week 72
  • Time to death and/or occurrence of new or recurrent AIDS-defining events [ Time Frame: entry to week 24, entry to week 72 ] [ Designated as safety issue: Yes ]
    To examine time to death and/or occurrence of new or recurrent AIDS-defining events
  • Changes in fasting blood glucose and cholesterol measures [ Time Frame: entry to week 24, entry to week 72 ] [ Designated as safety issue: Yes ]
    To examine changes in fasting blood glucose and cholesterol measures
  • Changes in monocyte and T cell immune activation [ Time Frame: entry to week 24, entry to week 48 ] [ Designated as safety issue: No ]
    To study changes in levels of immune activation in monocytes and T cells from entry to week 24 and week 72 and assess relationship with clinical, immunological and virological outcomes
  • Neurocognitive function [ Time Frame: entry to week 24, entry to week 72 ] [ Designated as safety issue: No ]
    To evaluate the neurocognitive function of HIV and hepatitis C (HCV) coinfected subjects undergoing antiretroviral therapy (ART)
  • CD4 count [ Time Frame: to week 24 and to week 72 ] [ Designated as safety issue: No ]
    To estimate the rates of HIV virologic suppression (plasma HIV RNA < 50 copies/mL) at week 24 and 72 of study in raltegravir-based and efavirenz-based regimens when given in combination with tenofovir and emtricitabine in anti-retroviral-naïve HIV-infected subjects co-infected with hepatitis C.
  • Overall safety and tolerability [ Time Frame: over 72 weeks ] [ Designated as safety issue: Yes ]
    To assess overall safety and tolerability of the two regimens
  • metabolic parameters [ Time Frame: over 24 weeks and over 72 weeks ] [ Designated as safety issue: No ]
    To assess changes in metabolic parameters (glucose, insulin resistance, total, LDL and HDL cholesterol, triglycerides) from entry to week 24 and from entry to week 72 in the two arms
  • adherence [ Time Frame: over 24 weeks and 72 weeks ] [ Designated as safety issue: No ]
    To assess adherence in the two arms
  • HIV/HCV viral dynamics [ Time Frame: over 24 weeks and 72 weeks ] [ Designated as safety issue: No ]
    To characterize HIV/HCV viral dynamics in plasma and in circulating cells of monocytic and lymphocytoic lineage in response to HIV therapy; to assess the dynamic relationship between these compartment and their relationship with clinical outcomes and with markers of immune reconstitution and immune activation
  • HIV drug resistance [ Time Frame: over 24 weeks and 72 weeks ] [ Designated as safety issue: No ]
    To assess patterns of genotypic HIV drug resistance associated with virologic failure
  • AIDS related mortality/morbidity [ Time Frame: over 24 weeks and 72 weeks ] [ Designated as safety issue: No ]
    To examine time to death and/or occurrence of AIDS-defining events in the two arms
  • Time to change in therapy [ Time Frame: Over 72 weeks ] [ Designated as safety issue: Yes ]
    To assess time to change in randomly assigned therapy in the two arms
  • Clinical outcome (in relationship to liver fibrosis stage) [ Time Frame: over 72 weeks ] [ Designated as safety issue: No ]
    To examine the impact of liver fibrosis stage (as calculated by Fib-4 index of liver fibrosis [1]) on changes in plasma HIV RNA and in CD4 count, rates of ALT elevations, overall safety and tolerability, changes in metabolic parameters*, adherence, HCV viral load*, time to death/AIDS-defining events and change in randomly assigned therapy
Not Provided
Not Provided
 
Hepatic Safety of Raltegravir Versus Efavirenz as HIV Therapy for Patients With HIV and HCV Coinfection
Hepatic Safety of Raltegravir-based and Efavirenz-based Antiretroviral Regimens in Antiretroviral-Naïve HIV-infected Subjects Co-Infected With Hepatitis C

The main objective is to evaluate the hepatic safety of raltegravir when compared to efavirenz, both in combination with tenofovir and emtricitabine as first-line HIV treatment in patients with HIV and hepatitis C coinfection.

The trial will recruit 80 treatment-naive HIV-infected patients with chronic hepatitis C coinfection from two HIV treatment centers in Vietnam. Patients will be randomized to receive either raltegravir or efavirenz, both in combination of tenofovir and emtricitabine, as first-line HIV therapy over a period of 72 weeks. The primary endpoint is the rate of alanine aminotransferase (ALT) elevation during the 72 week study period. Secondary endpoints include rates of virological suppression, CD4 count change, numbers of AIDS events and death, rates of fasting glucose and cholesterol measures, neurocognitive function and levels of immune activation. Patients will be followed monthly for the first 3 months and every 3 months thereafter. At the end of the trial period, patients will be transferred to the National HIV treatment program for continuation of HIV therapy.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Hepatitis C, Chronic
  • HIV Infection
  • Drug: Raltegravir
    Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Raltegravir 400 mg twice daily
    Other Name: Isentress
  • Drug: Efavirenz
    Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Efavirenz 600 mg po daily
    Other Name: Sustiva
  • Experimental: Raltegravir based therapy
    Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Raltegravir 400 mg twice daily
    Intervention: Drug: Raltegravir
  • Active Comparator: Efavirenz based therapy
    Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Efavirenz 600 mg po daily
    Intervention: Drug: Efavirenz
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
80
June 2017
December 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • HIV infected patients, age >18 years, meet Vietnam guideline to begin ART (CD4 count < 350 cells/mm3 and/or WHO stage III or IV disease)
  • Hepatitis C infection as documented by positive HCV antibodies and a detectable serum HCV RNA level
  • AST and ALT ≤ 2 x ULN (≤ 80 U/L)
  • Estimated creatinine clearance ≥ 60 mL/min

Exclusion Criteria:

  • Any prior ART
  • Positive Hepatitis B surface antigen
  • Clinical evidence of de-compensated cirrhosis (ascites, encephalopathy, esophageal bleeding)
  • Requirement for acute therapy for other AIDS-defining illness within 14 days prior to study entry
  • Currently on rifampicin therapy
  • In the first trimester of pregnancy, intent to become pregnant, or breast feeding during the study period
Both
18 Years and older
No
Contact: Thuy Le, MD 84-8-838-2338
Vietnam
 
NCT01147107
VHARP 001
Yes
University of Hawaii
University of Hawaii
  • Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
  • Viet Tiep General Hospital, Hai Phong, Vietnam
  • Oxford University Clinical Research Unit, Vietnam
Principal Investigator: Van Vinh Chau Nguyen, MD, PhD Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
Principal Investigator: Cecilia M Shikuma, M.D. University of Hawaii - Hawaii Center for AIDS (HICFA)
Study Director: Thuy Le, M.D. University of Hawaii, Oxford University Clinical Research Unit
University of Hawaii
September 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP