Hepatitis C, Chronic, HIV Infection
Conditions
Keywords
HIV/HCV co-infection, Antiretroviral therapy
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.
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.
Interventions
DRUGRaltegravir
Emtricitabine/tenofovir DF\* 200 mg/300 mg po daily + Raltegravir 400 mg twice daily
DRUGEfavirenz
Emtricitabine/tenofovir DF\* 200 mg/300 mg po daily + Efavirenz 600 mg po daily
Sponsors
Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
Viet Tiep Hospital
Oxford University Clinical Research Unit, Vietnam
University of Hawaii
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rates of Grade 2 and Higher Alanine Aminotransferase (ALT) Elevations | over week 72 | To estimate the rates of grade 2\*and higher ALT elevations in the two regimens. |
Countries
Vietnam
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Raltegravir Based Therapy Emtricitabine/tenofovir DF\* 200 mg/300 mg po daily + Raltegravir 400 mg twice daily
Raltegravir: Emtricitabine/tenofovir DF\* 200 mg/300 mg po daily + Raltegravir 400 mg twice daily | 38 |
| Efavirenz Based Therapy Emtricitabine/tenofovir DF\* 200 mg/300 mg po daily + Efavirenz 600 mg po daily
Efavirenz: Emtricitabine/tenofovir DF\* 200 mg/300 mg po daily + Efavirenz 600 mg po daily | 41 |
| Total | 79 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 5 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Raltegravir Based Therapy | Total | Efavirenz Based Therapy |
|---|---|---|---|
| Age, Continuous | 32 years | 32 years | 33 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 38 Participants | 79 Participants | 41 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Vietnam | 38 participants | 79 participants | 41 participants |
| Sex: Female, Male Female | 6 Participants | 10 Participants | 4 Participants |
| Sex: Female, Male Male | 32 Participants | 69 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 38 | 3 / 41 |
| other Total, other adverse events | 21 / 38 | 29 / 41 |
| serious Total, serious adverse events | 8 / 38 | 8 / 41 |
Outcome results
Primary
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.
Time frame: over week 72
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Raltegravir Based Therapy | Rates of Grade 2 and Higher Alanine Aminotransferase (ALT) Elevations | 24 Participants |
| Efavirenz Based Therapy | Rates of Grade 2 and Higher Alanine Aminotransferase (ALT) Elevations | 30 Participants |