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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Hepatic Safety of Raltegravir-based and Efavirenz-based Antiretroviral Regimens in Antiretroviral-Naïve HIV-infected Subjects Co-Infected With Hepatitis C

Conditions
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Hepatitis C, Chronic, HIV Infection

Intervention / Treatment
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* Drug: Raltegravir
* Drug: Efavirenz


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV/HCV co-infection, Antiretroviral therapy