HIV
Conditions
Keywords
Stribild, Genvoya, elvitegravir, Cerebrospinal Fluid, HIV
Brief summary
The project will have two tracks, one for participants who are currently taking elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate or E/C/F/tenofovir alafenamide (E/C/F/TDF or E/C/F/TAF) single-tablet regimen\* (STR) (Track A) and one for participants who will begin therapy with E/C/F/TDF or E/C/F/TAF STR during the study (Track B). Participants will take E/C/F/TDF and/or E/C/F/tenofovir alafenamide fumarate (E/C/F/TAF) STR\*\* (if available) for 24 weeks. \*Co-formulation of 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and 300 mg of tenofovir disoproxil fumarate. \*\*Co-formulation of 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and 10 mg of tenofovir alafenamide fumarate.
Detailed description
The proposed project will be a prospective, open-label treatment trial of 14 HIV-infected adults. Participants will be enrolled in two tracks. Track A will enroll participants who have been taking E/C/F/TDF to E/C/F/TAF for at least 12 weeks. Track B will enroll participants who are not taking ART and no prior exposure to elvitegravir and no genotypic drug resistance to any component of E/C/F/TDF to E/C/F/TAF. CSF and blood will be collected twice in Track A (two on-treatment assessments) and three times in Track B (one pre-treatment, two on-treatment assessments). If possible, we plan to time assessments to bridge the transition from E/C/F/TDF to E/C/F/TAF so that all participants will ideally have one CSF collection on each regimen, enabling a paired comparison of tenofovir concentrations between the two tenofovir formulations. We estimate that 28 on-treatment CSF collections will be sufficient to provide a small-sample estimate of the distribution of elvitegravir, tenofovir and TAF into CSF.
Interventions
Sponsors
Gilead Sciences
University at Buffalo
University of California, San Diego
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Adult men or women aged 18-60 years. Able and willing to provide informed consent. * Presence of HIV-1 infection as documented by a licensed ELISA test kit and confirmed by Western blot or HIV RNA. * Track A (Currently taking E/C/F/TDF or E/C/F/TAF): Taking E/C/F/TDF or E/C/F/TAF for at least 3 months prior to screening and undetectable plasma HIV-1 RNA (≤ 40 copies/mL) * Track B (Currently not taking ART): Off ART for at least 3 months. Prior exposure to TDF and FTC will be allowed but subjects must not have primary genotypic drug resistance mutations to elvitegravir, tenofovir, or emtricitabine (see
Exclusion criteria
) * Plasma HIV-1 RNA ≥ 5,000c/mL and CD4+ T-cell count ≥200cells/mm3.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Concentration of Elvitegravir in Cerebrospinal Fluid at Baseline | Baseline |
| Concentration of Elvitegravir in Cerebrospinal Fluid at Week 24 | Week 24 |
| Concentration of Tenofovir in Cerebrospinal Fluid at Baseline | Baseline |
| Concentration of Tenofovir in Cerebrospinal Fluid at Week 24 | Week 24 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Stribild Arm Stribild Arm is for participants taking Stribild at the time of study entry. Participants taking Stribild at the time of study entry will switch to Genvoya before the second PK.
Stribild: To be administered orally, once daily with food.
Genvoya: To be administered orally, once daily with food. | 9 |
| Genvoya Arm Genvoya Arm is for participants already taking Genvoya at the time of study entry. Participants taking Genvoya at the time of study entry will continue Genvoya for the second PK.
Genvoya: To be administered orally, once daily with food. | 5 |
| Untreated Arm Untreated Arm is for participants who are not taking ART at the time of study entry. Participants will start Stribild at entry and switch to Genvoya before the second PK.
Stribild: To be administered orally, once daily with food.
Genvoya: To be administered orally, once daily with food. | 0 |
| Total | 14 |
Baseline characteristics
| Characteristic | Stribild Arm | Genvoya Arm | Total |
|---|---|---|---|
| Age, Continuous | 34 years | 45 years | 34.5 years |
| CD4+ T-cell Count | 601 cells/µL | 784 cells/µL | 717 cells/µL |
| Plasma HIV RNA ≤ 40 copies/mL | 9 Participants | 5 Participants | 14 Participants |
| 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 | 1 Participants | 1 Participants | 2 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 | 8 Participants | 4 Participants | 12 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 8 Participants | 5 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 5 | 0 / 0 |
| other Total, other adverse events | 4 / 9 | 5 / 5 | 0 / 0 |
| serious Total, serious adverse events | 1 / 9 | 1 / 5 | 0 / 0 |
Outcome results
Primary
Concentration of Elvitegravir in Cerebrospinal Fluid at Baseline
Time frame: Baseline
Population: No participants enrolled in the Untreated Arm
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stribild Arm | Concentration of Elvitegravir in Cerebrospinal Fluid at Baseline | 4.3 ng/mL |
| Genvoya Arm | Concentration of Elvitegravir in Cerebrospinal Fluid at Baseline | 2.72 ng/mL |
Primary
Concentration of Elvitegravir in Cerebrospinal Fluid at Week 24
Time frame: Week 24
Population: No participants enrolled in the Untreated Arm
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stribild Arm | Concentration of Elvitegravir in Cerebrospinal Fluid at Week 24 | 5.90 ng/mL |
| Genvoya Arm | Concentration of Elvitegravir in Cerebrospinal Fluid at Week 24 | 3.09 ng/mL |
Primary
Concentration of Tenofovir in Cerebrospinal Fluid at Baseline
Time frame: Baseline
Population: No participants enrolled in the Untreated Arm
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stribild Arm | Concentration of Tenofovir in Cerebrospinal Fluid at Baseline | 3.03 ng/mL |
| Genvoya Arm | Concentration of Tenofovir in Cerebrospinal Fluid at Baseline | 0.49 ng/mL |
Primary
Concentration of Tenofovir in Cerebrospinal Fluid at Week 24
Time frame: Week 24
Population: No participants enrolled in the Untreated Arm
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stribild Arm | Concentration of Tenofovir in Cerebrospinal Fluid at Week 24 | 0.507 ng/mL |
| Genvoya Arm | Concentration of Tenofovir in Cerebrospinal Fluid at Week 24 | 0.481 ng/mL |