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

• ClinicalTrials.gov Identifier: NCT01147107
• Recruitment Status: Completed
• First Posted: June 22, 2010
• Results First Posted: August 13, 2021
• Last Update Posted: August 13, 2021
• Sponsor: University of Hawaii
• 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

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Hepatitis C, Chronic; HIV Infection	Drug: Raltegravir; Drug: Efavirenz	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Hepatic Safety of Raltegravir-based and Efavirenz-based Antiretroviral Regimens in Antiretroviral-Naïve HIV-infected Subjects Co-Infected With Hepatitis C
• Actual Study Start Date: February 2014
• Actual Primary Completion Date: June 1, 2016
• Actual Study Completion Date: June 1, 2021

Arms and Interventions

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 Name: 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 Name: Sustiva

Outcome Measures

Primary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Vietnam

Viet Tiep General Hospital

Hai Phong, Vietnam

Hospital for Tropical Diseases

Ho Chi Minh City, Vietnam

Sponsors and Collaborators

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

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

More Information

• Responsible Party: University of Hawaii
• ClinicalTrials.gov Identifier: NCT01147107
• Other Study ID Numbers: VHARP 001
• First Posted: June 22, 2010
• Results First Posted: August 13, 2021
• Last Update Posted: August 13, 2021
• Last Verified: July 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: IPD will be shared with other researchers upon request following the publication of the data. Researchers will contact the PI.

Keywords provided by University of Hawaii:

HIV/HCV co-infection; Antiretroviral therapy

Additional relevant MeSH terms:

Hepatitis C; Hepatitis C, Chronic; Hepatitis; Infections; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; RNA Virus Infections; Blood-Borne Infections; Communicable Diseases; Flaviviridae Infections; Hepatitis, Chronic; Chronic Disease; Disease Attributes; Pathologic Processes; Efavirenz; Raltegravir Potassium; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Anti-Infective Agents; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers