HCV Coinfection, Liver Disease, HIV
Conditions
Brief summary
Open-label, partially-randomized plasma and liver sampling study to assess hepatitis C virus (HCV) kinetics during treatment with two (Sofosbuvir/Velpatasvir) or three (Sofosbuvir/Velpatasvir/Voxilaprevir) direct acting antivirals (DAAs)
Detailed description
Primary Objective: The primary objective is to estimate the 1-week change in the proportion of HCV-infected hepatocytes in participants with HCV monoinfection and HIV/HCV coinfection on therapy with two or three DAAs with different mechanisms of action using single cell laser microdissection (scLCM). Secondary Objectives: Estimate the change over the first week in plasma HCV RNA in subjects with HCV monoinfected and HIV/HCV coinfected participants on therapy with two or three DAAs Estimate the 1 week change in the amount of HCV RNA per infected hepatocyte using scLCM on liver biopsy specimens, obtained just prior to treatment initiation (pre-treatment), and after the first week of DAA therapy. Estimate the change in the proportion of HCV-infected hepatocytes that express interferon-stimulated genes (ISGs) within the first week of DAA therapy using scLCM. Measure the change in expression of ISGs in non-parenchymal intrahepatic immune cells (Kupffer cells, plasmacytoid dendritic cells) within the first week of DAA therapy using scLCM. Exploratory Objectives: Estimate the 1 week change in expression of ISGs from peripheral blood mononucleated cells (PBMCs) within the first week of DAA+ribavirin (RBV) therapy using scLCM. Compare sequence(s) of HCV protease, nonstructural protein 5A (NS5A), and nonstructural protein 5B (NS5B) depending on the peripheral sequence) of intrahepatic HCV RNA in single cells and bulk tissue, before and during week 1 of DAA+RBV therapy. Estimate the week 1 change in the sizes and numbers of HCV-infected clusters on DAA therapy to test whether clearance of HCV-infected hepatocytes occurs in spatially random patterns or within specific clusters.
Interventions
DRUGSofosbuvir/Velpatasvir/Voxilaprevir [SOF/VEL/VOX]
antiviral therapy for HCV
antiviral therapy for HCV
Sponsors
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Participants must meet all of the following inclusion criteria to be eligible for participation 1. Ability and willingness of participant to provide written informed consent. 2. Men and women age ≥18 to ≤70 years at study entry 3. Body mass index (BMI) ≥ 18 kg/m2 4. HCV RNA ≥ 10,000 IU/mL at Screening 5. HCV genotype 1a at Screening or within 6 months of screening 6. Chronic HCV infection (≥ 6 months) documented by prior medical history 7. HCV treatment-naïve with no prior treatment with any IFN, RBV, or approved or experimental HCV-specific DAA 8. Absence of cirrhosis as defined as transient elastography (FibroScan®) liver stiffness measurement \< 12.5 kPa within 6 months of screening 9. The following laboratory values obtained within 42 days prior to study entry. • Hemoglobin \> 10 g/dL for men and \> 9 g/dL for women • Platelet count ≥90,000/mm3 • International normalized ratio (INR) ≤1.5 • Calculated creatinine clearance (CrCl) ≥ 30 mL/min • Alanine aminotransferase (ALT) and aspartate aminotransferase level ≤ 10 x upper limit of the normal range (ULN) • Total bilirubin \<3 mg/dL • Albumin ≥3.5 g/dL * CD4+ cell count ≥200 cells/uL and CD4+ cell percentage ≥14% within 42 days of study entry at any US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification \[HIV seropositive participants only\] * HIV RNA \< 400 copies/mL prior to study entry by any US laboratory that has a CLIA certification or its equivalent \[HIV seropositive participants only\] 10. On a qualifying antiretroviral therapy (ART) regimen which is permitted with SOF/VEL. This allows for antiretroviral regimen that does not include Efavirenz, Nevirapine, or Tipranavir. 11. Women of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day 0 prior to liver biopsy 12. All participants must agree not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization). 13. If participating in sexual activity that could lead to pregnancy, the participant (men and women) must also agree to use two reliable methods of contraception simultaneously while receiving study treatment and for 30 days after stopping study treatment. A combination of TWO of the following contraceptives MUST be used appropriately: • Condoms (male or female) with or without a spermicidal agent • Diaphragm or cervical cap with spermicide • IUD (intrauterine device) 14. Participants who are not of reproductive potential (women who have been post-menopausal for at least 24 consecutive months or have undergone hysterectomy, bilateral tubal ligation, and/or bilateral oophorectomy or men who have documented azoospermia) are eligible without requiring the use of contraceptives. Acceptable documentation of sterilization and menopause is specified below. Written or oral documentation communicated by clinician or clinician's staff of one of the following: * Physician report/letter * Laboratory report of azoospermia * Follicle stimulating hormone-release factor (FSH) measurement elevated into the menopausal range as established by the reporting laboratory. 15. Participants must be able to adhere to dosing instructions for study drug administration and able to complete the study schedule of assessments, in the opinion of the investigator.
Exclusion criteria
Subjects who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy | Pre-treatment, Day 7 | Estimate the total number of HCV-infected Hepatocytes (virus burden) for each participant between pre-treatment liver biopsy and post treatment liver biopsy samples using HCV Quantitative real time PCR. Comparison of total number of HCV-infected Hepatocytes (virus burden) were reported between HCV mono infection and co infection groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reduction Over the First Week in Plasma HCV RNA | Pre-treatment, up to 1 week | During one week after treatment with direct-acting antivirals, the decline from the baseline plasma HCV RNA levels observed for each individual participant using HCV Quantitative real time PCR. The level of HCV RNA decline compared to those treated with Sofosbuvir/Velpatasvir (SOF/VEL) vs Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) and between HCV mono infection and HIV/HCV co infection groups. |
| Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM). | Pre-treatment, up to 1 week | Total number of hepatocytes that express interferon-stimulated genes (ISGs) were estimated using Quantitative real time PCR for each participant on pre-treatment and post treatment liver biopsy samples. Comparison of total number of hepatocytes that express interferon-stimulated genes (ISGs) were reported between HCV mono infection and co infection groups. |
| Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy. | Pre-treatment, after first week | The HCV RNA levels (viral burden) from each infected hepatocytes were measured using Quantitative Real-Time Polymerase Chain Reaction (PCR) from each participants at pre-treatment and post-treatment. The level of HCV RNA (viral burden) decline were reported from intracellular hepatocytes and compared to those treated with Sofosbuvir/Velpatasvir (SOF/VEL) vs Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) and between HCV mono infection and HIV/HCV co infection groups. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A Monoinfected: Sofosbuvir/Velpatasvir/Voxilaprevir SOF/VEL/VOX days 0-7 Paired liver biopsy at days 0 and 7 (cohort 1) or days 0 and 4 (cohort 2). SOF/VEL days 8 (week 2) through 84 (week 12). Post-treatment follow up through week 12. | 5 |
| Group B Monoinfected: Sofosbuvir/Velpatasvir (SOF/VEL) days 0 through 7 and Paired liver biopsy at days 0 and 7 (cohort 1) or days 0 and 4 (cohort 2). SOF/VEL on day 8 (week 2) through 84 (week 12) . Post-Treatment follow up through week 12. | 5 |
| Group C HIV/HCV Co-infection: Sofosbuvir/Velpatasvir (SOF/VEL) days 0 through 7 and Paired liver biopsy at days 0 and 7 (cohort 1) or days 0 and 4 (cohort 2). SOF/VEL on day 8 (week 2) through 84 (week 12) . Post-Treatment follow up through week 12. | 5 |
| Total | 15 |
Baseline characteristics
| Characteristic | Group A | Total | Group C | Group B |
|---|---|---|---|---|
| Age, Continuous | 50 years | 50.5 years | 54.6 years | 47 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 15 Participants | 5 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 12 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 3 Participants | 0 Participants | 2 Participants |
| Region of Enrollment United States | 5 participants | 15 participants | 5 participants | 5 participants |
| Sex: Female, Male Female | 2 Participants | 7 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 3 Participants | 8 Participants | 3 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 5 | 0 / 5 |
| other Total, other adverse events | 2 / 5 | 2 / 5 | 3 / 5 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 | 0 / 5 |
Outcome results
Primary
Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy
Estimate the total number of HCV-infected Hepatocytes (virus burden) for each participant between pre-treatment liver biopsy and post treatment liver biopsy samples using HCV Quantitative real time PCR. Comparison of total number of HCV-infected Hepatocytes (virus burden) were reported between HCV mono infection and co infection groups.
Time frame: Pre-treatment, Day 7
Population: Overall number analyzed is the total hepatocytes analyzed in specific arms but numbers in rows represent only HCV positive Hepatocytes
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group A | Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy | Participant 1 (Group A) Participant 1 (Group B) Participant 1 (Group C)pre trea | 45 Hepatocytes |
| Group A | Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy | Participant 1 (Group A) Participant 1 (Group B) Participant 1 (Group C)pos trea | 2 Hepatocytes |
| Group A | Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy | Participant 2 (Group A) Participant 2 (Group B) Participant 2 (Group C)pre trea | 53 Hepatocytes |
| Group A | Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy | Participant 2 (Group A) Participant 2 (Group B) Participant 2 (Group C)pos trea | 0 Hepatocytes |
| Group A | Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy | Participant 3 (Group A) Participant 3 (Group B) Participant 3 (Group C)pretreat | 18 Hepatocytes |
| Group A | Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy | Participant 3 (Group A) Participant 3 (Group B) Participant 3 (Group C)postreat | 2 Hepatocytes |
| Group A | Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy | Participant 4 (Group A) Participant 4 (Group B) Participant 4 (Group C)pre trea | 109 Hepatocytes |
| Group A | Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy | Participant 4 (Group A) Participant 4 (Group B) Participant 4 (Group C)pos trea | 3 Hepatocytes |
| Group A | Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy | Participant 5 (Group A) Participant 5 (Group B) Participant 5 (Group C)pretre | 126 Hepatocytes |
| Group A | Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy | Participant 5 (Group A) Participant 5 (Group B) Participant 5 (Group C)postre | 18 Hepatocytes |
| Group B | Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy | Participant 5 (Group A) Participant 5 (Group B) Participant 5 (Group C)pretre | 4 Hepatocytes |
| Group B | Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy | Participant 1 (Group A) Participant 1 (Group B) Participant 1 (Group C)pre trea | 16 Hepatocytes |
| Group B | Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy | Participant 3 (Group A) Participant 3 (Group B) Participant 3 (Group C)postreat | 9 Hepatocytes |
| Group B | Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy | Participant 3 (Group A) Participant 3 (Group B) Participant 3 (Group C)pretreat | 212 Hepatocytes |
| Group B | Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy | Participant 1 (Group A) Participant 1 (Group B) Participant 1 (Group C)pos trea | 5 Hepatocytes |
| Group B | Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy | Participant 5 (Group A) Participant 5 (Group B) Participant 5 (Group C)postre | 1 Hepatocytes |
| Group B | Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy | Participant 4 (Group A) Participant 4 (Group B) Participant 4 (Group C)pos trea | 1 Hepatocytes |
| Group B | Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy | Participant 2 (Group A) Participant 2 (Group B) Participant 2 (Group C)pre trea | 11 Hepatocytes |
| Group B | Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy | Participant 4 (Group A) Participant 4 (Group B) Participant 4 (Group C)pre trea | 24 Hepatocytes |
| Group B | Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy | Participant 2 (Group A) Participant 2 (Group B) Participant 2 (Group C)pos trea | 1 Hepatocytes |
| Group C | Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy | Participant 4 (Group A) Participant 4 (Group B) Participant 4 (Group C)pos trea | 0 Hepatocytes |
| Group C | Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy | Participant 2 (Group A) Participant 2 (Group B) Participant 2 (Group C)pos trea | 3 Hepatocytes |
| Group C | Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy | Participant 3 (Group A) Participant 3 (Group B) Participant 3 (Group C)pretreat | 216 Hepatocytes |
| Group C | Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy | Participant 3 (Group A) Participant 3 (Group B) Participant 3 (Group C)postreat | 24 Hepatocytes |
| Group C | Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy | Participant 5 (Group A) Participant 5 (Group B) Participant 5 (Group C)pretre | 74 Hepatocytes |
| Group C | Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy | Participant 4 (Group A) Participant 4 (Group B) Participant 4 (Group C)pre trea | 13 Hepatocytes |
| Group C | Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy | Participant 1 (Group A) Participant 1 (Group B) Participant 1 (Group C)pre trea | 290 Hepatocytes |
| Group C | Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy | Participant 5 (Group A) Participant 5 (Group B) Participant 5 (Group C)postre | 12 Hepatocytes |
| Group C | Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy | Participant 1 (Group A) Participant 1 (Group B) Participant 1 (Group C)pos trea | 7 Hepatocytes |
| Group C | Total Number of HCV-infected Hepatocytes Measured in Liver Tissue Obtained by Liver Biopsy at Day 0 (Pre-treatment) and at Day 7 of Antiviral Therapy | Participant 2 (Group A) Participant 2 (Group B) Participant 2 (Group C)pre trea | 33 Hepatocytes |
Secondary
Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy.
The HCV RNA levels (viral burden) from each infected hepatocytes were measured using Quantitative Real-Time Polymerase Chain Reaction (PCR) from each participants at pre-treatment and post-treatment. The level of HCV RNA (viral burden) decline were reported from intracellular hepatocytes and compared to those treated with Sofosbuvir/Velpatasvir (SOF/VEL) vs Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) and between HCV mono infection and HIV/HCV co infection groups.
Time frame: Pre-treatment, after first week
Population: Amount of HCV RNA levels from individual hepatocytes for each participant obtained at pre-treatment and post treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Group A | Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy. | Participant 2 (Group A) Participant 2 (Group B) Participant 2 (Group C)Post treat | 0 International unit (IU) per hepatocyte |
| Group A | Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy. | Participant 1 (Group A) Participant 1 (Group B) Participant 1 (Group C) Post treat | 20.91 International unit (IU) per hepatocyte |
| Group A | Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy. | Participant 4 (Group A) Participant 4 (Group B) Participant 4 (Group C)Pre treat | 29.25 International unit (IU) per hepatocyte |
| Group A | Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy. | Participant 3 (Group A) Participant 3 (Group B) Participant 3 (Group C)Pre treat | 10.35 International unit (IU) per hepatocyte |
| Group A | Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy. | Participant 1 (Group A) Participant 1 (Group B) Participant 1 (Group C) Pre treat | 8.61 International unit (IU) per hepatocyte |
| Group A | Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy. | Participant 3 (Group A) Participant 3 (Group B) Participant 3 (Group C)Post treat | 14.76 International unit (IU) per hepatocyte |
| Group A | Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy. | Participant 5 (Group A) Participant 5 (Group B) Participant 5 (Group C)Post treat | 14.55 International unit (IU) per hepatocyte |
| Group A | Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy. | Participant 2 (Group A) Participant 2 (Group B) Participant 2 (Group C)Pre treat | 19.74 International unit (IU) per hepatocyte |
| Group A | Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy. | Participant 5 (Group A) Participant 5 (Group B) Participant 5 (Group C)Pre treat | 15.3 International unit (IU) per hepatocyte |
| Group A | Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy. | Participant 4 (Group A) Participant 4 (Group B) Participant 4 (Group C)Post treat | 9.15 International unit (IU) per hepatocyte |
| Group B | Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy. | Participant 5 (Group A) Participant 5 (Group B) Participant 5 (Group C)Pre treat | 2.36 International unit (IU) per hepatocyte |
| Group B | Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy. | Participant 1 (Group A) Participant 1 (Group B) Participant 1 (Group C) Pre treat | 7.57 International unit (IU) per hepatocyte |
| Group B | Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy. | Participant 1 (Group A) Participant 1 (Group B) Participant 1 (Group C) Post treat | 2.83 International unit (IU) per hepatocyte |
| Group B | Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy. | Participant 2 (Group A) Participant 2 (Group B) Participant 2 (Group C)Pre treat | 11.04 International unit (IU) per hepatocyte |
| Group B | Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy. | Participant 2 (Group A) Participant 2 (Group B) Participant 2 (Group C)Post treat | 12.93 International unit (IU) per hepatocyte |
| Group B | Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy. | Participant 3 (Group A) Participant 3 (Group B) Participant 3 (Group C)Pre treat | 27.18 International unit (IU) per hepatocyte |
| Group B | Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy. | Participant 3 (Group A) Participant 3 (Group B) Participant 3 (Group C)Post treat | 9.25 International unit (IU) per hepatocyte |
| Group B | Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy. | Participant 4 (Group A) Participant 4 (Group B) Participant 4 (Group C)Pre treat | 3.45 International unit (IU) per hepatocyte |
| Group B | Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy. | Participant 4 (Group A) Participant 4 (Group B) Participant 4 (Group C)Post treat | 0 International unit (IU) per hepatocyte |
| Group B | Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy. | Participant 5 (Group A) Participant 5 (Group B) Participant 5 (Group C)Post treat | 2.27 International unit (IU) per hepatocyte |
| Group C | Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy. | Participant 1 (Group A) Participant 1 (Group B) Participant 1 (Group C) Pre treat | 32.7 International unit (IU) per hepatocyte |
| Group C | Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy. | Participant 4 (Group A) Participant 4 (Group B) Participant 4 (Group C)Pre treat | 14.25 International unit (IU) per hepatocyte |
| Group C | Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy. | Participant 2 (Group A) Participant 2 (Group B) Participant 2 (Group C)Pre treat | 18.36 International unit (IU) per hepatocyte |
| Group C | Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy. | Participant 5 (Group A) Participant 5 (Group B) Participant 5 (Group C)Post treat | 4.09 International unit (IU) per hepatocyte |
| Group C | Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy. | Participant 4 (Group A) Participant 4 (Group B) Participant 4 (Group C)Post treat | 0 International unit (IU) per hepatocyte |
| Group C | Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy. | Participant 5 (Group A) Participant 5 (Group B) Participant 5 (Group C)Pre treat | 5.49 International unit (IU) per hepatocyte |
| Group C | Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy. | Participant 3 (Group A) Participant 3 (Group B) Participant 3 (Group C)Pre treat | 30 International unit (IU) per hepatocyte |
| Group C | Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy. | Participant 1 (Group A) Participant 1 (Group B) Participant 1 (Group C) Post treat | 37.8 International unit (IU) per hepatocyte |
| Group C | Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy. | Participant 3 (Group A) Participant 3 (Group B) Participant 3 (Group C)Post treat | 15.72 International unit (IU) per hepatocyte |
| Group C | Amount of HCV RNA Per Infected Hepatocyte Using Single Cell Laser Micro Dissection (scLCM) on Liver Biopsy Specimens, Obtained Just Prior to Treatment Initiation (Pre-treatment), and After the First Week of DAA Therapy. | Participant 2 (Group A) Participant 2 (Group B) Participant 2 (Group C)Post treat | 8.16 International unit (IU) per hepatocyte |
Secondary
Reduction Over the First Week in Plasma HCV RNA
During one week after treatment with direct-acting antivirals, the decline from the baseline plasma HCV RNA levels observed for each individual participant using HCV Quantitative real time PCR. The level of HCV RNA decline compared to those treated with Sofosbuvir/Velpatasvir (SOF/VEL) vs Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) and between HCV mono infection and HIV/HCV co infection groups.
Time frame: Pre-treatment, up to 1 week
Population: Decline plasma levels of HCV RNA from each participant obtained over the first week.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Group A | Reduction Over the First Week in Plasma HCV RNA | Participant 4 (Group A) Participant 4 (Group B) Participant 4 (Group C) | 6617.5 IU/ml |
| Group A | Reduction Over the First Week in Plasma HCV RNA | Participant 2 (Group A) Participant 2 (Group B) Participant 2 (Group C) | 217.75 IU/ml |
| Group A | Reduction Over the First Week in Plasma HCV RNA | Participant 1 (Group A) Participant 1 (Group B) Participant 1 (Group C) | 631 IU/ml |
| Group A | Reduction Over the First Week in Plasma HCV RNA | Participant 3 (Group A) Participant 3 (Group B) Participant 3 (Group C) | 1029.75 IU/ml |
| Group A | Reduction Over the First Week in Plasma HCV RNA | Participant 5 (Group A) Participant 5 (Group B) Participant 5 (Group C) | 2506.5 IU/ml |
| Group B | Reduction Over the First Week in Plasma HCV RNA | Participant 3 (Group A) Participant 3 (Group B) Participant 3 (Group C) | 1348500 IU/ml |
| Group B | Reduction Over the First Week in Plasma HCV RNA | Participant 4 (Group A) Participant 4 (Group B) Participant 4 (Group C) | 551.5 IU/ml |
| Group B | Reduction Over the First Week in Plasma HCV RNA | Participant 5 (Group A) Participant 5 (Group B) Participant 5 (Group C) | 627.5 IU/ml |
| Group B | Reduction Over the First Week in Plasma HCV RNA | Participant 1 (Group A) Participant 1 (Group B) Participant 1 (Group C) | 2240 IU/ml |
| Group B | Reduction Over the First Week in Plasma HCV RNA | Participant 2 (Group A) Participant 2 (Group B) Participant 2 (Group C) | 884.75 IU/ml |
| Group C | Reduction Over the First Week in Plasma HCV RNA | Participant 5 (Group A) Participant 5 (Group B) Participant 5 (Group C) | 12992.5 IU/ml |
| Group C | Reduction Over the First Week in Plasma HCV RNA | Participant 3 (Group A) Participant 3 (Group B) Participant 3 (Group C) | 5327.5 IU/ml |
| Group C | Reduction Over the First Week in Plasma HCV RNA | Participant 2 (Group A) Participant 2 (Group B) Participant 2 (Group C) | 635.5 IU/ml |
| Group C | Reduction Over the First Week in Plasma HCV RNA | Participant 4 (Group A) Participant 4 (Group B) Participant 4 (Group C) | 65075 IU/ml |
| Group C | Reduction Over the First Week in Plasma HCV RNA | Participant 1 (Group A) Participant 1 (Group B) Participant 1 (Group C) | 14817.5 IU/ml |
Secondary
Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM).
Total number of hepatocytes that express interferon-stimulated genes (ISGs) were estimated using Quantitative real time PCR for each participant on pre-treatment and post treatment liver biopsy samples. Comparison of total number of hepatocytes that express interferon-stimulated genes (ISGs) were reported between HCV mono infection and co infection groups.
Time frame: Pre-treatment, up to 1 week
Population: Total number of hepatocytes that express interferon-stimulated genes (ISGs) between pre and post treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group A | Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM). | Participant 1 (Group A) Participant 1 (Group B) Participant 1 (Group C) Pre Treatment | 14 ISG positive hepatocytes |
| Group A | Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM). | Participant 1 (Group A) Participant 1 (Group B) Participant 1 (Group C) Post Treatment | 8 ISG positive hepatocytes |
| Group A | Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM). | Participant 2 (Group A) Participant 2 (Group B) Participant 2 (Group C) Pre Treatment | 57 ISG positive hepatocytes |
| Group A | Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM). | Participant 2 (Group A) Participant 2 (Group B) Participant 2 (Group C) Post Treatment | 62 ISG positive hepatocytes |
| Group A | Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM). | Participant 3 (Group A) Participant 3 (Group B) Participant 3 (Group C) Pre Treatment | 78 ISG positive hepatocytes |
| Group A | Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM). | Participant 3 (Group A) Participant 3 (Group B) Participant 3 (Group C) Post Treatment | 83 ISG positive hepatocytes |
| Group A | Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM). | Participant 4 (Group A) Participant 4 (Group B) Participant 4 (Group C) Pre Treatment | 71 ISG positive hepatocytes |
| Group A | Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM). | Participant 4 (Group A) Participant 4 (Group B) Participant 4 (Group C) Post Treatment | 71 ISG positive hepatocytes |
| Group A | Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM). | Participant 5 (Group A) Participant 5 (Group B) Participant 5 (Group C) Pre Treatment | 79 ISG positive hepatocytes |
| Group A | Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM). | Participant 5 (Group A) Participant 5 (Group B) Participant 5 (Group C) Post Treatment | 72 ISG positive hepatocytes |
| Group B | Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM). | Participant 5 (Group A) Participant 5 (Group B) Participant 5 (Group C) Pre Treatment | 67 ISG positive hepatocytes |
| Group B | Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM). | Participant 1 (Group A) Participant 1 (Group B) Participant 1 (Group C) Pre Treatment | 71 ISG positive hepatocytes |
| Group B | Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM). | Participant 3 (Group A) Participant 3 (Group B) Participant 3 (Group C) Post Treatment | 46 ISG positive hepatocytes |
| Group B | Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM). | Participant 3 (Group A) Participant 3 (Group B) Participant 3 (Group C) Pre Treatment | 66 ISG positive hepatocytes |
| Group B | Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM). | Participant 1 (Group A) Participant 1 (Group B) Participant 1 (Group C) Post Treatment | 68 ISG positive hepatocytes |
| Group B | Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM). | Participant 5 (Group A) Participant 5 (Group B) Participant 5 (Group C) Post Treatment | 66 ISG positive hepatocytes |
| Group B | Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM). | Participant 4 (Group A) Participant 4 (Group B) Participant 4 (Group C) Post Treatment | 27 ISG positive hepatocytes |
| Group B | Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM). | Participant 2 (Group A) Participant 2 (Group B) Participant 2 (Group C) Pre Treatment | 36 ISG positive hepatocytes |
| Group B | Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM). | Participant 4 (Group A) Participant 4 (Group B) Participant 4 (Group C) Pre Treatment | 49 ISG positive hepatocytes |
| Group B | Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM). | Participant 2 (Group A) Participant 2 (Group B) Participant 2 (Group C) Post Treatment | 24 ISG positive hepatocytes |
| Group C | Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM). | Participant 4 (Group A) Participant 4 (Group B) Participant 4 (Group C) Post Treatment | 63 ISG positive hepatocytes |
| Group C | Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM). | Participant 2 (Group A) Participant 2 (Group B) Participant 2 (Group C) Post Treatment | 40 ISG positive hepatocytes |
| Group C | Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM). | Participant 3 (Group A) Participant 3 (Group B) Participant 3 (Group C) Pre Treatment | 55 ISG positive hepatocytes |
| Group C | Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM). | Participant 3 (Group A) Participant 3 (Group B) Participant 3 (Group C) Post Treatment | 57 ISG positive hepatocytes |
| Group C | Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM). | Participant 5 (Group A) Participant 5 (Group B) Participant 5 (Group C) Pre Treatment | 34 ISG positive hepatocytes |
| Group C | Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM). | Participant 4 (Group A) Participant 4 (Group B) Participant 4 (Group C) Pre Treatment | 36 ISG positive hepatocytes |
| Group C | Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM). | Participant 1 (Group A) Participant 1 (Group B) Participant 1 (Group C) Pre Treatment | 41 ISG positive hepatocytes |
| Group C | Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM). | Participant 5 (Group A) Participant 5 (Group B) Participant 5 (Group C) Post Treatment | 42 ISG positive hepatocytes |
| Group C | Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM). | Participant 1 (Group A) Participant 1 (Group B) Participant 1 (Group C) Post Treatment | 68 ISG positive hepatocytes |
| Group C | Total Number of HCV-infected Hepatocytes That Express Interferon-stimulated Genes (ISGs) Within the First Week of DAA Therapy Using Single Cell Laser Micro Dissection (scLCM). | Participant 2 (Group A) Participant 2 (Group B) Participant 2 (Group C) Pre Treatment | 39 ISG positive hepatocytes |