Hepatitis C Infection, HIV
Conditions
Keywords
HCV, HIV, Thailand, pegylated interferon, ribavirin
Brief summary
This is a study of HCV treatment using the standard regimen of pegylated-interferon plus ribavirin in HIV co-infected patients participating in the PHPT cohort study. The treatment will be implemented in conjunction with gastro-enterologists/hepatologists by internists responsible for the participant's HIV treatment. Chronic hepatitis C virus (HCV) infection is responsible for several severe and life threatening complications, which are worsened by HIV co-infection. HIV-HCV co-infected patients are at a higher risk of death compared to HIV mono-infected individuals, even if HIV replication is suppressed on antiretroviral treatment. The goal of HCV antiviral treatment is to cure HCV infection. Curing HCV infection allows fibrosis regression, improved clinical outcomes. In addition, individuals who have been cured are no longer contagious to other individuals, therefore widespread access to HCV treatment may contribute to the control of the HCV epidemic. A combination of injectable pegylated-interferon with oral ribavirin is currently the recommended regimen for the treatment of hepatitis C in the setting of HIV co-infection. They are administered for 24 weeks in HCV mono-infected patients but need to be administered for one year in HIV-HCV co-infected patients. Newer drugs, such as the first generation HCV protease inhibitors (boceprevir, telaprevir), administered concomitantly, are used in patients who have not been cured using peg-interferon + ribavirin, and may allow for shorter treatment. PRIMARY OBJECTIVE 1\. To determine the percentage of patients according to genotypes with sustained virological response 6 months after treatment discontinuation (SVR). HCV TREATMENT * Peg-interferon alpha 2-b (a subcutaneous injection of 1.5 micrograms/kg once a week) * Ribavirin dosing according to HCV genotype and body weight; dose adjustment in case of anemia. A total of 60 patients could be enrolled in the study: 15 HCV-HIV co-infected patients in a first part (starting in August 2014) and 45 patients in a second part, depending on funding.
Detailed description
Study Population Screening: HIV infected patients with a positive anti-HCV test will be approached for screening if they are at least 18 years old, participate in the PHPT cohort study, have evidence of control of HIV replication and have a CD4 cell count ≥200 cells/mm3 if currently receiving antiretroviral HIV treatment (on the same anti-HIV regimen for at least 12 weeks); or HIV RNA load ≤5000 copies/ml CD4 cells ≥500 cells/mm3if not receiving antiretroviral treatment. Inclusion Criteria * Evidence of chronic HCV infection for at least 6 months before study entry (at least one detectable HCV viral load, i.e. ≥17 IU/mL, with an antibody test positive at least 6 months before the HCV RNA load result) * Fibrosis Stage F2-3-4 determined by transient elastography (Fibroscan or other similar equipment). During the first part of the study, priority will be given to patients with Fibrosis Stage F2-3. * Negative pregnancy test (on the day of inclusion). Main exclusion criteria * Anemia and thrombocytopenia * Severe liver damage, advanced stage cirrhosis or cancer * Uncontrolled diabetes, Uncontrolled thyroid dysfunction * Retinopathy * Creatinine clearance \<50 mL/min (Cockcroft) * Disease associated with the immune system * Significant heart problems * Severe neuropsychiatric conditions * Contra-indication to study treatment (including pregnancy or lack of effective contraception in the participant or female partner) * Other exclusion criteria related to the use of ribavirin and peg-interferon * Any conditions that, in the investigator's judgment, may compromise the follow up. Follow up After HCV treatment initiation, patients will be monitored for safety and antiviral efficacy at 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 weeks (end of treatment) and 6 months after treatment discontinuation. Treatment will be discontinued earlier in patients who do not achieve early viral response, i.e. a decrease of at least 2 log10 HCV RNA IU/mL after the first 12 weeks of HCV therapy.
Interventions
DRUGPeg-interferon + ribavirin under HIV physician supervision
Peg-interferon + ribavirin under HIV physician supervision
Sponsors
Ministry of Health, Thailand
Institut de Recherche pour le Developpement
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Evidence of chronic HCV infection for at least 6 months before study entry (at least one detectable HCV viral load, i.e. ≥17 IU/mL, with an antibody test positive at least 6 months before the HCV RNA load result) * Fibrosis Stage F2-3-4 determined by transient elastography (Fibroscan or other similar equipment). During the first part of the study, priority will be given to patients with Fibrosis Stage F2-3. * Negative pregnancy test (on the day of inclusion).
Exclusion criteria
* Anemia and thrombocytopenia * Severe liver damage, advanced stage cirrhosis or cancer * Uncontrolled diabetes, Uncontrolled thyroid dysfunction * Retinopathy * Creatinine clearance \<50 mL/min (Cockcroft) * Disease associated with the immune system * Significant heart problems * Severe neuropsychiatric conditions Contra-indication to study treatment (including pregnancy or lack of effective contraception in the participant or female partner) * Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Sustained Virological Response 6 Months After Treatment Discontinuation | 6 months after end of treatment, i.e. 1.5 years after treatment initiation | Number of Participants with Sustained Virological Response 6 Months After Treatment Discontinuation, |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least a Serious Adverse Events Associated With Study Treatment (Peg-interferon and Ribavirin) | From initiation of treatment to 6 months after treatment discontinuation | Number of participants with at least a serious adverse events associated with study treatment (peg-interferon and ribavirin). |
| Number of Participants Grouped by HIV-1 RNA Concentrations | At time of treatment discontinuation (whatever its date) and 6 months thereafter | Number of participants grouped by HIV-1 RNA concentrations (Detected vs. Not Detected). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Completed the First 24 and 48 Weeks of Treatment | From initiation of treatment to the first 48 weeks of treatment | Number of participants completed the first 24 and 48 weeks of treatment. |
| Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | From initiation of treatment to the first 48 weeks of treatment | Number of participants with ribavirin compliance at ≥ 95%, 80% - 95%, and \< 80%. |
| Number of Adverse Events by Severity Grade | From initiation of treatment to 6 months after treatment discontinuation | Number of adverse events (AE) by severity grade. The severity grading scale is based on the DAIDS grading table, the grading scale ranging from grades 1 to 5: Grade 1 indicates a mild event, Grade 2 indicates a moderate event, Grade 3 indicates a severe event, Grade 4 indicates a potentially life-threatening event, and Grade 5 indicates death. |
| Number of Participants Able to Perform Self-injections of Peg-interferon | From initiation of treatment to the first 48 weeks of treatment | Number of participants able to perform self-injections of peg-interferon. |
Countries
Thailand
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PegINF-ribavirin Peg-interferon + ribavirin under HIV physician supervision Peg-interferon alpha 2-b initial dosing is 1.5 micrograms/kg (subcutaneous injection) once a week
Ribavirin initial dosing in the morning and in the evening:
1. For genotypes 2, 3: ribavirin 400 mg (i.e. 800 mg daily).
2. For genotypes 1, 4, 5 and 6:
* 800 mg/day, if bodyweight \<65 kg,
* 1000 mg/day, if bodyweight between 66-80 kg,
* 1200 mg/day, if bodyweight between 81-105 kg,
* 1400 mg/day, if bodyweight \>105 kg.
Duration: 48 weeks
Peg-interferon + ribavirin under HIV physician supervision: Peg-interferon + ribavirin under HIV physician supervision | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of Efficacy | 3 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | PegINF-ribavirin |
|---|---|
| Age, Continuous | 44.2 years |
| Body Mass Index | 21.8 kg/m^2 |
| HCV genotypes Gt 1a | 2 Participants |
| HCV genotypes Gt 1b | 8 Participants |
| HCV genotypes Gt 3a | 5 Participants |
| HCV genotypes Gt 3b | 1 Participants |
| HCV genotypes Gt 6a/b | 1 Participants |
| HCV genotypes Gt 6c-l | 1 Participants |
| HCV RNA | 5.83 log10 IU/mL |
| IL 28B polymorphism CC | 14 Participants |
| IL 28B polymorphism CT | 4 Participants |
| Liver fibrosis stage F2 | 1 Participants |
| Liver fibrosis stage F3 | 4 Participants |
| Liver fibrosis stage F4 | 13 Participants |
| Race/Ethnicity, Customized Asian | 18 Participants |
| Region of Enrollment Thailand | 18 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 18 |
| other Total, other adverse events | 13 / 18 |
| serious Total, serious adverse events | 2 / 18 |
Outcome results
Primary
Number of Participants With Sustained Virological Response 6 Months After Treatment Discontinuation
Number of Participants with Sustained Virological Response 6 Months After Treatment Discontinuation,
Time frame: 6 months after end of treatment, i.e. 1.5 years after treatment initiation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PegINF-ribavirin | Number of Participants With Sustained Virological Response 6 Months After Treatment Discontinuation | 10 Participants |
Secondary
Number of Participants Grouped by HIV-1 RNA Concentrations
Number of participants grouped by HIV-1 RNA concentrations (Detected vs. Not Detected).
Time frame: At time of treatment discontinuation (whatever its date) and 6 months thereafter
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PegINF-ribavirin | Number of Participants Grouped by HIV-1 RNA Concentrations | HIV-1 RNA not detected | 16 Participants |
| PegINF-ribavirin | Number of Participants Grouped by HIV-1 RNA Concentrations | HIV-1 RNA detected | 1 Participants |
| PegINF-ribavirin | Number of Participants Grouped by HIV-1 RNA Concentrations | Missing | 1 Participants |
Secondary
Number of Participants With at Least a Serious Adverse Events Associated With Study Treatment (Peg-interferon and Ribavirin)
Number of participants with at least a serious adverse events associated with study treatment (peg-interferon and ribavirin).
Time frame: From initiation of treatment to 6 months after treatment discontinuation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PegINF-ribavirin | Number of Participants With at Least a Serious Adverse Events Associated With Study Treatment (Peg-interferon and Ribavirin) | 1 Participants |
Other Pre-specified
Number of Adverse Events by Severity Grade
Number of adverse events (AE) by severity grade. The severity grading scale is based on the DAIDS grading table, the grading scale ranging from grades 1 to 5: Grade 1 indicates a mild event, Grade 2 indicates a moderate event, Grade 3 indicates a severe event, Grade 4 indicates a potentially life-threatening event, and Grade 5 indicates death.
Time frame: From initiation of treatment to 6 months after treatment discontinuation
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PegINF-ribavirin | Number of Adverse Events by Severity Grade | AE grade 1 | 18 events |
| PegINF-ribavirin | Number of Adverse Events by Severity Grade | AE grade 2 | 7 events |
| PegINF-ribavirin | Number of Adverse Events by Severity Grade | AE grade 3 | 1 events |
Other Pre-specified
Number of Participants Able to Perform Self-injections of Peg-interferon
Number of participants able to perform self-injections of peg-interferon.
Time frame: From initiation of treatment to the first 48 weeks of treatment
Population: 1. subject discontinued treatment after week 1~2. subjects discontinued treatment after week 12~1 subject discontinued treatment after week 24
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| PegINF-ribavirin | Number of Participants Able to Perform Self-injections of Peg-interferon | Week 0 to Week 12 | PegINF injected | 17 Participants |
| PegINF-ribavirin | Number of Participants Able to Perform Self-injections of Peg-interferon | Week 0 to Week 12 | PegINF not injected | 0 Participants |
| PegINF-ribavirin | Number of Participants Able to Perform Self-injections of Peg-interferon | Week 12 to Week 16 | PegINF injected | 16 Participants |
| PegINF-ribavirin | Number of Participants Able to Perform Self-injections of Peg-interferon | Week 12 to Week 16 | PegINF not injected | 1 Participants |
| PegINF-ribavirin | Number of Participants Able to Perform Self-injections of Peg-interferon | Week 16 to Week 28 | PegINF injected | 15 Participants |
| PegINF-ribavirin | Number of Participants Able to Perform Self-injections of Peg-interferon | Week 16 to Week 28 | PegINF not injected | 0 Participants |
| PegINF-ribavirin | Number of Participants Able to Perform Self-injections of Peg-interferon | Week 28 to Week 32 | PegINF injected | 13 Participants |
| PegINF-ribavirin | Number of Participants Able to Perform Self-injections of Peg-interferon | Week 28 to Week 32 | PegINF not injected | 1 Participants |
| PegINF-ribavirin | Number of Participants Able to Perform Self-injections of Peg-interferon | Week 32 to Week 48 | PegINF injected | 14 Participants |
| PegINF-ribavirin | Number of Participants Able to Perform Self-injections of Peg-interferon | Week 32 to Week 48 | PegINF not injected | 0 Participants |
Other Pre-specified
Number of Participants Completed the First 24 and 48 Weeks of Treatment
Number of participants completed the first 24 and 48 weeks of treatment.
Time frame: From initiation of treatment to the first 48 weeks of treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PegINF-ribavirin | Number of Participants Completed the First 24 and 48 Weeks of Treatment | Completed the first 24 weeks of treatment | 14 Participants |
| PegINF-ribavirin | Number of Participants Completed the First 24 and 48 Weeks of Treatment | Completed the first 48 weeks of treatment | 14 Participants |
Other Pre-specified
Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80%
Number of participants with ribavirin compliance at ≥ 95%, 80% - 95%, and \< 80%.
Time frame: From initiation of treatment to the first 48 weeks of treatment
Population: 1. subject discontinued treatment after week 1~2. subjects discontinued treatment after week 12~1 subject discontinued treatment after week 24
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 32 to Week 36 | Compliance ≥ 95% | 14 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 0 to Week 2 | Compliance < 80% | 0 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 0 to Week 2 | Compliance 80% - 95% | 2 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 0 to Week 2 | Compliance ≥ 95% | 15 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 2 to Week 4 | Compliance < 80% | 1 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 2 to Week 4 | Compliance 80% - 95% | 1 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 2 to Week 4 | Compliance ≥ 95% | 15 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 4 to Week 12 | Compliance < 80% | 0 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 4 to Week 12 | Compliance 80% - 95% | 0 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 4 to Week 12 | Compliance ≥ 95% | 17 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 12 to Week 16 | Compliance < 80% | 0 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 12 to Week 16 | Compliance 80% - 95% | 1 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 12 to Week 16 | Compliance ≥ 95% | 16 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 16 to Week 20 | Compliance < 80% | 0 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 16 to Week 20 | Compliance 80% - 95% | 0 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 16 to Week 20 | Compliance ≥ 95% | 15 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 20 to Week 24 | Compliance < 80% | 0 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 20 to Week 24 | Compliance 80% - 95% | 2 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 20 to Week 24 | Compliance ≥ 95% | 13 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 24 to Week 28 | Compliance < 80% | 1 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 24 to Week 28 | Compliance 80% - 95% | 0 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 24 to Week 28 | Compliance ≥ 95% | 14 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 28 to Week 32 | Compliance < 80% | 1 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 28 to Week 32 | Compliance 80% - 95% | 0 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 28 to Week 32 | Compliance ≥ 95% | 13 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 32 to Week 36 | Compliance < 80% | 0 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 32 to Week 36 | Compliance 80% - 95% | 0 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 36 to Week 44 | Compliance < 80% | 0 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 36 to Week 44 | Compliance 80% - 95% | 1 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 36 to Week 44 | Compliance ≥ 95% | 13 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 44 to Week 48 | Compliance < 80% | 0 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 44 to Week 48 | Compliance 80% - 95% | 0 Participants |
| PegINF-ribavirin | Number of Participants With Ribavirin Compliance at ≥ 95%, 80% - 95%, and < 80% | Week 44 to Week 48 | Compliance ≥ 95% | 14 Participants |