HIV, HBV
Conditions
Keywords
HIV, HBV, Coinfection
Brief summary
This study will assess the efficacy, safety, and tolerability of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) in human immunodeficiency virus (HIV)/hepatitis B virus (HBV) coinfected adults. Participants will be enrolled into two cohorts: * Cohort 1: HIV/HBV coinfected adults who are HIV treatment-naive and HBV treatment-naive * Cohort 2: HIV/HBV coinfected adults who are HIV-suppressed
Interventions
DRUGE/C/F/TAF
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food
Sponsors
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Both Cohorts 1 and 2: * The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures * HIV/HBV co-infected adult males and non-pregnant and non-lactating females * No evidence of hepatocellular carcinoma (HCC) or clinical or imaging evidence of cirrhosis (ascites, variceal bleeding, encephalopathy). \--- Subjects should have documentation of an abdominal ultrasound in the 12 months prior to screening, or an abdominal ultrasound at screening, demonstrating the absence of cirrhosis and HCC. * Acute Hepatitis A virus (HAV) immunoglobulin M (IgM) negative * Hepatitis C virus (HCV) Ab negative, or HCV Ab positive with negative HCV RNA * Hepatitis D virus (HDV) Ab negative, or HDV Ab positive with negative HDV RNA * Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault formula * CD4+ count of \> 200 cells/μL * Chronic HBV infection as defined by * HBsAg positive for ≥ 6 months Or * HBsAg positive at screening and either hepatitis B e antigen (HBeAg) or HBV DNA positive ≥ 6 months Or * At screening: positive total hepatitis B core antibody (HBcAb) and negative immunoglobulin M antibody to hepatitis B core antigen (HBcIgM) antibody, and * HBsAg positive, or * HBeAg positive, or * HBV DNA positive * Cohort 1 (HIV and HBV treatment naive) only: * No current or prior anti-HIV treatment, including antiretroviral medications received for prevention (PrEP), or post exposure prophylaxis (PEP) * No current or prior anti-HBV treatment * Plasma HIV-1 RNA level ≥ 500 copies/mL at screening * Screening HBV DNA ≥ 3 log10 IU/mL and \< 9 log10 IU/mL * Cohort 2 (HIV suppressed) only: * Receiving current antiretroviral regimen for at least 4 consecutive months * No current or prior regimen containing 3 active anti-HBV agents (i.e. cannot be on tenofovir alafenamide (TDF)/emtricitabine (FTC)/Entecavir or TDF/lamivudine(3TC)/Entecavir) * Maintained plasma HIV-1 RNA \< 50 copies/mL for 6 consecutive months prior to and at the time of the screening visit. Unconfirmed virologic evaluation of ≥ 50 copies/mL after previously reaching viral suppression (transient detectable viremia, or blip) and prior to screening is acceptable * Documented positive HIV antibody test * Screening HBV DNA \< 9 log10 IU/mL Key
Exclusion criteria
* Females who are breastfeeding * Positive serum pregnancy test (female of childbearing potential) * Have an implanted defibrillator or pacemaker * Current alcohol or substance use * A history of malignancy within the past 5 years (prior to screening) or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive carcinoma. * Received solid organ or bone marrow transplant * Any history of, or current evidence of, clinical hepatic decompensation (e.g., ascites, encephalopathy or variceal hemorrhage). * Significant bone disease (e.g., osteomalacia, chronic osteomyelitis, osteogenesis imperfecta, osteochondroses), or multiple bone fractures * Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1 * Subjects on hemodialysis, other forms of renal replacement therapy, or on treatment for underlying kidney diseases (including prednisolone, and dexamethasone) * Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements * Investigational agents (unless approved by Gilead Sciences). Participation in any other clinical trial without prior approval from the sponsor is prohibited while participating in this trial Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Plasma HIV-1 RNA Level < 50 Copies/mL | Week 24 | The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. |
| Percentage of Participants With Plasma HBV DNA Levels < 29 IU/mL | Week 24 | The percentage of participants with HBV DNA \< 29 IU/mL at Week 24 was calculated using the missing = failure method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Normalized Alanine Aminotransferase (ALT) at Week 24 | Baseline; Week 24 | ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit. |
| Percentage of Participants With Normalized ALT at Week 48 | Baseline; Week 48 | ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit. |
| Percentage of Participants With Seroconversion to Hepatitis B Surface Antibody (Anti-HBs) at Week 24 | Baseline; Week 24 | Seroconversion to antibody is defined as (1) antigen loss and (2) positive postbaseline antibody value. Missing = excluded method. |
| Percentage of Participants With Seroconversion to Anti-HBs at Week 48 | Baseline; Week 48 | Seroconversion to antibody is defined as (1) antigen loss and (2) positive postbaseline antibody value. Missing = excluded method. |
| Percentage of Participants With Plasma HIV-1 RNA Level < 50 Copies/mL | Week 48 | The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. |
| Percentage of Participants With Seroconversion to Anti-HBe at Week 48 | Baseline; Week 48 | Seroconversion to antibody is defined as (1) antigen loss and (2) positive postbaseline antibody value. Missing = excluded method. |
| Change From Baseline in FibroTest® Score at Week 24 | Baseline; Week 24 | The FibroTest® score is used to assess liver fibrosis. Scores range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis. |
| Change From Baseline in FibroTest® Score at Week 48 | Baseline; Week 48 | The FibroTest® score is used to assess liver fibrosis. Scores range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis. |
| Percentage of Participants With Seroconversion to Hepatitis B e Antibody (Anti-HBe) at Week 24 | Baseline; Week 24 | Seroconversion to antibody is defined as (1) antigen loss and (2) positive postbaseline antibody value. Missing = excluded method. |
| Percentage of Participants With Plasma HBV DNA Levels < 29 IU/mL | Week 48 | The percentage of participants with HBV DNA \< 29 IU/mL at Week 48 was calculated using the missing = failure method. |
Countries
Canada, Japan, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in North America and Japan. The first participant was screened on 25 February 2014. The last study visit occurred on 26 October 2016.
Pre-assignment details
113 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| HIV/HBV Treatment-Naive HIV/HBV coinfected participants who were HIV treatment-naive and HBV treatment-naive received E/C/F/TAF (150/150/200/10 mg) FDC tablet once daily with food for 48 weeks. | 3 |
| HIV-Suppressed HIV/HBV coinfected participants who were HIV-suppressed received E/C/F/TAF (150/150/200/10 mg) FDC tablet once daily with food for 48 weeks. | 74 |
| Total | 77 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Enrolled and Never Treated | 1 | 1 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Withdrew Consent | 0 | 4 |
Baseline characteristics
| Characteristic | HIV/HBV Treatment-Naive | HIV-Suppressed | Total |
|---|---|---|---|
| Age, Continuous | 27 years STANDARD_DEVIATION 4 | 49 years STANDARD_DEVIATION 7.8 | 49 years STANDARD_DEVIATION 8.9 |
| Alanine Aminotransferase (ALT) | 84 U/L STANDARD_DEVIATION 38.9 | 31 U/L STANDARD_DEVIATION 21.1 | 33 U/L STANDARD_DEVIATION 23.9 |
| Fibrotest® Score | 0.27 units on a scale | 0.35 units on a scale | 0.34 units on a scale |
| HBV DNA | 8.31 log10 IU/mL STANDARD_DEVIATION 0.416 | 1.49 log10 IU/mL STANDARD_DEVIATION 0.883 | 1.75 log10 IU/mL STANDARD_DEVIATION 1.588 |
| HBV DNA Category < 29 IU/mL | 0 participants | 64 participants | 64 participants |
| HBV DNA Category ≥ 29 IU/mL | 3 participants | 10 participants | 13 participants |
| Hepatitis B e-Antibody Status Borderline | 0 participants | 5 participants | 5 participants |
| Hepatitis B e-Antibody Status Negative | 3 participants | 43 participants | 46 participants |
| Hepatitis B e-Antibody Status Positive | 0 participants | 26 participants | 26 participants |
| Hepatitis B Surface Antigen Status Negative | 0 participants | 3 participants | 3 participants |
| Hepatitis B Surface Antigen Status Positive | 3 participants | 71 participants | 74 participants |
| HIV-1 RNA | 4.20 log10 copies/mL STANDARD_DEVIATION 1.242 | 1.29 log10 copies/mL STANDARD_DEVIATION 0.068 | 1.41 log10 copies/mL STANDARD_DEVIATION 0.606 |
| HIV-1 RNA Category < 50 copies/mL | 0 participants | 73 participants | 73 participants |
| HIV-1 RNA Category ≥ 50 copies/mL | 3 participants | 1 participants | 4 participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Asian | 2 participants | 7 participants | 9 participants |
| Race/Ethnicity, Customized Black | 0 participants | 14 participants | 14 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 participants | 12 participants | 12 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 3 participants | 62 participants | 65 participants |
| Race/Ethnicity, Customized Other | 0 participants | 2 participants | 2 participants |
| Race/Ethnicity, Customized White | 1 participants | 50 participants | 51 participants |
| Region of Enrollment Canada | 0 participants | 10 participants | 10 participants |
| Region of Enrollment Japan | 2 participants | 2 participants | 4 participants |
| Region of Enrollment United States | 1 participants | 62 participants | 63 participants |
| Sex: Female, Male Female | 0 Participants | 6 Participants | 6 Participants |
| Sex: Female, Male Male | 3 Participants | 68 Participants | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 74 |
| other Total, other adverse events | 2 / 3 | 51 / 74 |
| serious Total, serious adverse events | 0 / 3 | 12 / 74 |
Outcome results
Primary
Percentage of Participants With Plasma HBV DNA Levels < 29 IU/mL
The percentage of participants with HBV DNA \< 29 IU/mL at Week 24 was calculated using the missing = failure method.
Time frame: Week 24
Population: Full Analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HIV/HBV Treatment-Naive | Percentage of Participants With Plasma HBV DNA Levels < 29 IU/mL | 33.3 percentage of participants |
| HIV-Suppressed | Percentage of Participants With Plasma HBV DNA Levels < 29 IU/mL | 86.1 percentage of participants |
Primary
Percentage of Participants With Plasma HIV-1 RNA Level < 50 Copies/mL
The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Time frame: Week 24
Population: Full Analysis Set: participants who were enrolled, received at least 1 dose of study drug, had at least 1 post-Day 1 plasma HBV DNA or HIV-1 RNA result while on study, and had no major protocol violations from the eligibility criteria.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HIV/HBV Treatment-Naive | Percentage of Participants With Plasma HIV-1 RNA Level < 50 Copies/mL | 100.0 percentage of participants |
| HIV-Suppressed | Percentage of Participants With Plasma HIV-1 RNA Level < 50 Copies/mL | 94.4 percentage of participants |
Secondary
Change From Baseline in FibroTest® Score at Week 24
The FibroTest® score is used to assess liver fibrosis. Scores range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis.
Time frame: Baseline; Week 24
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| HIV/HBV Treatment-Naive | Change From Baseline in FibroTest® Score at Week 24 | -0.19 units on a scale |
| HIV-Suppressed | Change From Baseline in FibroTest® Score at Week 24 | -0.02 units on a scale |
Secondary
Change From Baseline in FibroTest® Score at Week 48
The FibroTest® score is used to assess liver fibrosis. Scores range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis.
Time frame: Baseline; Week 48
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| HIV/HBV Treatment-Naive | Change From Baseline in FibroTest® Score at Week 48 | -0.15 units on a scale |
| HIV-Suppressed | Change From Baseline in FibroTest® Score at Week 48 | -0.07 units on a scale |
Secondary
Percentage of Participants With Normalized Alanine Aminotransferase (ALT) at Week 24
ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit.
Time frame: Baseline; Week 24
Population: Participants in the Full Analysis Set who had ALT values above the normal range at baseline were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HIV/HBV Treatment-Naive | Percentage of Participants With Normalized Alanine Aminotransferase (ALT) at Week 24 | 100.0 percentage of participants |
| HIV-Suppressed | Percentage of Participants With Normalized Alanine Aminotransferase (ALT) at Week 24 | 50.0 percentage of participants |
Secondary
Percentage of Participants With Normalized ALT at Week 48
ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit.
Time frame: Baseline; Week 48
Population: Participants in the Full Analysis Set who had ALT values above the normal range at baseline were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HIV/HBV Treatment-Naive | Percentage of Participants With Normalized ALT at Week 48 | 66.7 percentage of participants |
| HIV-Suppressed | Percentage of Participants With Normalized ALT at Week 48 | 40.0 percentage of participants |
Secondary
Percentage of Participants With Plasma HBV DNA Levels < 29 IU/mL
The percentage of participants with HBV DNA \< 29 IU/mL at Week 48 was calculated using the missing = failure method.
Time frame: Week 48
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HIV/HBV Treatment-Naive | Percentage of Participants With Plasma HBV DNA Levels < 29 IU/mL | 66.7 percentage of participants |
| HIV-Suppressed | Percentage of Participants With Plasma HBV DNA Levels < 29 IU/mL | 91.7 percentage of participants |
Secondary
Percentage of Participants With Plasma HIV-1 RNA Level < 50 Copies/mL
The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Time frame: Week 48
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HIV/HBV Treatment-Naive | Percentage of Participants With Plasma HIV-1 RNA Level < 50 Copies/mL | 66.7 percentage of participants |
| HIV-Suppressed | Percentage of Participants With Plasma HIV-1 RNA Level < 50 Copies/mL | 91.7 percentage of participants |
Secondary
Percentage of Participants With Seroconversion to Anti-HBe at Week 48
Seroconversion to antibody is defined as (1) antigen loss and (2) positive postbaseline antibody value. Missing = excluded method.
Time frame: Baseline; Week 48
Population: Participants in the Full Analysis Set with available data were analyzed who had positive antigen and negative antibody at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HIV/HBV Treatment-Naive | Percentage of Participants With Seroconversion to Anti-HBe at Week 48 | 33.3 percentage of participants |
| HIV-Suppressed | Percentage of Participants With Seroconversion to Anti-HBe at Week 48 | 0 percentage of participants |
Secondary
Percentage of Participants With Seroconversion to Anti-HBs at Week 48
Seroconversion to antibody is defined as (1) antigen loss and (2) positive postbaseline antibody value. Missing = excluded method.
Time frame: Baseline; Week 48
Population: Participants in the Full Analysis Set with available data were analyzed who had positive antigen and negative antibody at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HIV/HBV Treatment-Naive | Percentage of Participants With Seroconversion to Anti-HBs at Week 48 | 0 percentage of participants |
| HIV-Suppressed | Percentage of Participants With Seroconversion to Anti-HBs at Week 48 | 1.4 percentage of participants |
Secondary
Percentage of Participants With Seroconversion to Hepatitis B e Antibody (Anti-HBe) at Week 24
Seroconversion to antibody is defined as (1) antigen loss and (2) positive postbaseline antibody value. Missing = excluded method.
Time frame: Baseline; Week 24
Population: Participants in the Full Analysis Set with available data were analyzed who had positive antigen and negative antibody at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HIV/HBV Treatment-Naive | Percentage of Participants With Seroconversion to Hepatitis B e Antibody (Anti-HBe) at Week 24 | 33.3 percentage of participants |
| HIV-Suppressed | Percentage of Participants With Seroconversion to Hepatitis B e Antibody (Anti-HBe) at Week 24 | 3.3 percentage of participants |
Secondary
Percentage of Participants With Seroconversion to Hepatitis B Surface Antibody (Anti-HBs) at Week 24
Seroconversion to antibody is defined as (1) antigen loss and (2) positive postbaseline antibody value. Missing = excluded method.
Time frame: Baseline; Week 24
Population: Participants in the Full Analysis Set with available data were analyzed who had positive antigen and negative antibody at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HIV/HBV Treatment-Naive | Percentage of Participants With Seroconversion to Hepatitis B Surface Antibody (Anti-HBs) at Week 24 | 0 percentage of participants |
| HIV-Suppressed | Percentage of Participants With Seroconversion to Hepatitis B Surface Antibody (Anti-HBs) at Week 24 | 1.4 percentage of participants |