Hepatitis C, Human Immunodeficiency Virus
Conditions
Keywords
hepatitis C virus (HCV), Maraviroc, Human immunodeficiency virus (HCV)
Brief summary
This is a single-site, longitudinal, open-label, interventional study for evaluating the effect of maraviroc on hepatitis C viral levels in patients infected with both hepatitis C and human immunodeficiency virus (HIV) and taking antiretroviral therapy for HIV.
Detailed description
Recently, in-vitro studies (experiments performed in a laboratory, not on a person) have demonstrated that maraviroc, a medication that is used in human immunodeficiency (HIV) therapy, appears to have significant hepatitis C antiviral effect, comparable to sofosbuvir-a potent anti-hepatitis C medication. In this study, the investigators will evaluate the antiviral effect of maraviroc on hepatitis C virus in people infected with both hepatitis C and HIV, and whom have never been treated for hepatitis with direct antiviral agents. Participants will take maraviroc for 4 weeks in addition to their regular HIV antiretrovirals (ART). The investigators will measure the hepatitis C viral load before, during, and after the 4-week maraviroc time.
Interventions
DRUGMaraviroc
Participants will receive 4 weeks of maraviroc (dosing based on concomitant HIV antiretroviral regimen). Serial measurements of HCV viral load will be obtained before, during, and after maraviroc exposure. Study duration will be approximately 12 to 16 weeks.
Sponsors
ViiV Healthcare
University of Maryland, Baltimore
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 18 years old 2. Hepatitis C-infected without plans to undergo hepatitis C treatment for duration of the study 3. Human immunodeficiency virus (HIV) infected 4. Currently receiving anti-retroviral therapy with HIV viral load \<50 IU/ml for ≥ 12 months a. One virologic blip ≤ 400 copies/ml permissible within the 12 months 5. CD4 T cell counts \> 100 cells/mm3 6. Non-cirrhotics and cirrhotics can be included 7. Willing to sign informed consent
Exclusion criteria
1. Age \< 18 2. Unable to comply with study visits, research study visits, or is planning to relocate during the study. 3. Have any condition that the investigator considers a contraindication to study participation 4. Pregnancy or breast feeding 5. Decompensated liver disease (Child-Pugh C) 6. Imminent treatment for hepatitis C infection 7. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>2.5 times the upper limits of normal 8. Concomitant use of drugs known to impact or be impacted in terms of pharmacokinetics or drug-drug interactions with either raltegravir, dolutegravir, or maraviroc. This includes: * Inducers of UGT1A1 (such as rifampin, phenytoin, phenobarbital rifabutin, St. John's wort) * Cytochrome P3A inhibitors (such as ketoconazole, itraconazole, clarithromycin, nefazodone, and telithromycin) * Cytochrome P3A inducers (such as rifampin, carbamazepine, phenobarbital and phenytoin)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Change in Hepatitis C Viral Load From Baseline to 4 Weeks of Maraviroc or No Maraviroc | Baseline to 4 weeks | Hepatitis C viral load was measured before starting maraviroc, and at 4 weeks of maraviroc. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hepatitis C Viral Loads From Baseline to Day 7 on Maraviroc | 7 days | HCV viral load was measured before starting and at 7 days of maraviroc. Among participants that received Maraviroc in the first 4 weeks, HCV viral load was measured before first dose at day 0 and at day 7. Among participants that received Maraviroc in week 8 to 12, HCV viral load measured at day 56 before taking the first dose of Maraviroc and at day 63 (week 9) of study. |
Countries
United States
Participant flow
Recruitment details
Participants enrolled at the clinical research unit at the University of Maryland, Baltimore between June 2017 to April 2018
Participants by arm
| Arm | Count |
|---|---|
| Maraviroc First, Then no Maraviroc Participants first received maraviroc, 150mg to 600mg (dose based on concomitant HIV antiretroviral regimen) twice a day for 4 weeks. After a washout period of 4 weeks, they then received no maraviroc for 4 weeks. | 5 |
| No Maraviroc First, Then Maraviroc Participants first received no maraviroc for 4 weeks. After a washout period of 4 weeks, they then received maraviroc, 150mg to 600mg (dose based on concomitant HIV antiretroviral regimen) twice a day for 4 weeks. Participants are then seen for their last visit 4 weeks after their last dose of maraviroc. | 4 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention (4 Weeks) | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Maraviroc First, Then no Maraviroc | No Maraviroc First, Then Maraviroc | Total |
|---|---|---|---|
| Age, Continuous | 56.6 Years STANDARD_DEVIATION 3.1 | 55.8 Years STANDARD_DEVIATION 9.7 | 56.2 Years STANDARD_DEVIATION 6.8 |
| Alanine transaminase | 39.6 International Units/ml STANDARD_DEVIATION 21.2 | 31.8 International Units/ml STANDARD_DEVIATION 2.6 | 36.1 International Units/ml STANDARD_DEVIATION 15.7 |
| Hepatitis C viral load | 1734274 International Units/ml STANDARD_DEVIATION 949012 | 2411068 International Units/ml STANDARD_DEVIATION 1093469 | 2035071 International Units/ml STANDARD_DEVIATION 1012880 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 4 Participants | 9 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 United States | 5 participants | 4 participants | 9 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 9 |
| other Total, other adverse events | 3 / 9 | 1 / 9 |
| serious Total, serious adverse events | 1 / 9 | 0 / 9 |
Outcome results
Primary
The Change in Hepatitis C Viral Load From Baseline to 4 Weeks of Maraviroc or No Maraviroc
Hepatitis C viral load was measured before starting maraviroc, and at 4 weeks of maraviroc.
Time frame: Baseline to 4 weeks
Population: All participants who received at least one dose of each intervention and completed all study visits were included in the final analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc | The Change in Hepatitis C Viral Load From Baseline to 4 Weeks of Maraviroc or No Maraviroc | HCV viral load at baseline | 2035071 International Units/ml | Standard Deviation 1012880 |
| Maraviroc | The Change in Hepatitis C Viral Load From Baseline to 4 Weeks of Maraviroc or No Maraviroc | HCV viral load at 4 weeks | 2082302 International Units/ml | Standard Deviation 1673228 |
| Maraviroc | The Change in Hepatitis C Viral Load From Baseline to 4 Weeks of Maraviroc or No Maraviroc | Change in HCV viral load at 4 weeks | 47231 International Units/ml | Standard Deviation 805651.4 |
| No Maraviroc | The Change in Hepatitis C Viral Load From Baseline to 4 Weeks of Maraviroc or No Maraviroc | HCV viral load at baseline | 2027648 International Units/ml | Standard Deviation 1411027 |
| No Maraviroc | The Change in Hepatitis C Viral Load From Baseline to 4 Weeks of Maraviroc or No Maraviroc | HCV viral load at 4 weeks | 1216383 International Units/ml | Standard Deviation 769289.8 |
| No Maraviroc | The Change in Hepatitis C Viral Load From Baseline to 4 Weeks of Maraviroc or No Maraviroc | Change in HCV viral load at 4 weeks | -811264 International Units/ml | Standard Deviation 1357476 |
Comparison: Null hypothesis is that there is no difference in change in HCV viral load between Maraviroc and No Maravirocp-value: 0.13t-test, 2 sided
Secondary
Change in Hepatitis C Viral Loads From Baseline to Day 7 on Maraviroc
HCV viral load was measured before starting and at 7 days of maraviroc. Among participants that received Maraviroc in the first 4 weeks, HCV viral load was measured before first dose at day 0 and at day 7. Among participants that received Maraviroc in week 8 to 12, HCV viral load measured at day 56 before taking the first dose of Maraviroc and at day 63 (week 9) of study.
Time frame: 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maraviroc | Change in Hepatitis C Viral Loads From Baseline to Day 7 on Maraviroc | 2035071 International Units/ml | Standard Deviation 1012880 |
| No Maraviroc | Change in Hepatitis C Viral Loads From Baseline to Day 7 on Maraviroc | 2138768 International Units/ml | Standard Deviation 1732285 |
Comparison: Null hypothesis is that there is no difference in HCV viral load between baseline and 7 days of maraviroc.p-value: >0.5t-test, 2 sided