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.

Study Overview

• Status: Completed
• Conditions: HIV Infection; Hepatitis C, Chronic
• Intervention / Treatment: Drug: Raltegravir; Drug: Efavirenz

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 4

Contacts and Locations

Study Locations

• Vietnam
  • Hai Phong, Vietnam
    • Viet Tiep General Hospital
  • Ho Chi Minh City, Vietnam
    • Hospital For Tropical Diseases

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Raltegravir based therapy; Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Raltegravir 400 mg twice daily	Drug: Raltegravir; Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Raltegravir 400 mg twice daily; Other Names: Isentress
Active Comparator: Efavirenz based therapy; Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Efavirenz 600 mg po daily	Drug: Efavirenz; Emtricitabine/tenofovir DF* 200 mg/300 mg po daily + Efavirenz 600 mg po daily; Other Names: Sustiva

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rates of Grade 2 and Higher Alanine Aminotransferase (ALT) Elevations	To estimate the rates of grade 2*and higher ALT elevations in the two regimens.	over week 72

Collaborators and Investigators

• Sponsor: University of Hawaii
• Collaborators: Oxford University Clinical Research Unit, Vietnam; Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam; Viet Tiep General Hospital, Hai Phong, Vietnam
• Investigators: 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

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2014
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2021

Study Registration Dates

• First Submitted: June 16, 2010
• First Submitted That Met QC Criteria: June 16, 2010
• First Posted (Estimate): June 22, 2010

Study Record Updates

• Last Update Posted (Actual): August 13, 2021
• Last Update Submitted That Met QC Criteria: July 21, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Antiretroviral therapy; HIV/HCV co-infection
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Hepatitis C; Hepatitis C, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; HIV Integrase Inhibitors; Integrase Inhibitors; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Raltegravir Potassium; Efavirenz
• Other Study ID Numbers: VHARP 001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD will be shared with other researchers upon request following the publication of the data. Researchers will contact the PI.