HIV-1 Infection
Conditions
Brief summary
The primary objective of this study is to evaluate the efficacy of oral weekly islatravir (ISL) in combination with lenacapavir (LEN) in virologically suppressed people with HIV (PWH) at Week 24.
Interventions
DRUGISL
Capsules administered orally without regard to food
DRUGLEN
Tablets administered orally without regard to food
DRUGB/F/TAF
Tablets administered orally without regard to food
DRUGISL/LEN FDC
Tablets administered orally without regard to food
Sponsors
Gilead Sciences
Merck Sharp & Dohme LLC
Study design
Allocation
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: * Received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for ≥ 24 weeks at screening. * Documented plasma human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) \< 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL) for ≥ 24 weeks before and at screening. * Plasma HIV-1 RNA \< 50 copies/mL at screening. Key
Exclusion criteria
* History of prior virologic failure while receiving treatment for HIV-1. * Prior use of, or exposure to, islatravir (ISL) or lenacapavir (LEN). * Active, serious infections requiring parenteral therapy \< 30 days before randomization. * Active or occult hepatitis B virus (HBV) coinfection, defined as hepatitis B core antibody (HBcAb) positive, hepatitis B surface antigen (HBsAg) positive, or HBV deoxyribonucleic acid (DNA) positive as determined by the central laboratory. * Active hepatitis C virus (HCV) coinfection, defined as detectable HCV RNA. * Any of the following laboratory values at screening: * Creatinine clearance (CLcr) ≤ 30 mL/min according to the Cockcroft-Gault formula * CD4+ T-cells \< 200 cells/mm\^3 (Cohort 1); CD4+ T-cells \< 350 cells/mm\^3 (cohort 2). * Absolute lymphocyte count \< 900 cells/mm\^3 (cohort 2). * Individuals of childbearing potential (as defined in protocol) who have a positive serum pregnancy test at screening or positive urine and serum pregnancy tests at Day 1 prior to study drug administration. * Individuals who plan to continue breastfeeding during the study. * Documented historical or screening resistance reports showing nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) or non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs) resistance mutations in reverse transcriptase, including M184V/I (Cohort 2). Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 24 as Determined by the US Food and Drug Administration (FDA)-Defined Snapshot Algorithm | Week 24 | The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with the applicable study drug discontinuation status. Week 24 window was between Day 148 and 189 (inclusive). Percentages were rounded off. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm | Week 12 | The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 12 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with the applicable study drug discontinuation status. Week 12 window was between Day 71 and 105 (inclusive). Percentages were rounded off. |
| Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm | Week 48 | The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with the applicable study drug discontinuation status. Week 48 window was between Day 316 and 378 (inclusive). Percentages were rounded off. |
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm | Week 12 | The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 12 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with the applicable study drug discontinuation status. Week 12 window was between Day 71 and 105 (inclusive). Percentages were rounded off. |
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Determined by the US FDA-defined Snapshot Algorithm | Week 24 | The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with the applicable study drug discontinuation status. Week 24 window was between Day 148 and 189 (inclusive). Percentages were rounded off. |
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm | Week 48 | The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with the applicable study drug discontinuation status. Week 48 window was between Day 316 and 378 (inclusive). Percentages were rounded off. |
| Change From Baseline in Clusters of Differentiation 4 (CD4)+ Cell Count at Week 12 | Baseline and Week 12 | — |
| Change From Baseline in CD4+ Cell Count at Week 24 | Baseline and Week 24 | — |
| Percentage of Participants Experiencing Treatment-Emergent Adverse Events Leading to Study Drug Discontinuation | Up to 5 years | TEAEs were defined as 1 or both of any AEs leading to premature discontinuation of study drug, or any AEs with an onset date on or after the study drug start date and no later than the last exposure date after permanent discontinuation of the study drug. Percentages were rounded off. |
| Cohort 1: Plasma Concentrations for ISL | Anytime postdose at Week 4 | — |
| Cohort 2: Pharmacokinetic (PK) Parameter: Cmax of Islatravir (ISL) | Anytime post dose on Day 1 and at either Week 12 or Week 18 | Cmax was defined as the maximum observed concentration of drug. |
| Cohort 2: PK Parameter: Tmax of ISL | Anytime post dose on Day 1 and at either Week 12 or Week 18 | Tmax was defined as the time (observed time point) of Cmax. |
| Cohort 2: PK Parameter: Ctau of ISL | Anytime post dose at either Week 12 or Week 18 | Ctau was defined as the observed drug concentration at the end of the dosing interval. |
| Cohort 2: PK Parameter: AUCtau of ISL | Anytime post dose at either Week 12 or Week 18 | AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). |
| Plasma Concentrations for LEN | Anytime postdose at Week 4 | — |
| Cohort 2: Pharmacokinetic (PK) Parameter: Cmax of LEN | Anytime post dose on Day 1, Day 2 and at either Week 12 or 18 | Cmax was defined as the maximum observed concentration of drug. |
| Cohort 2: PK Parameter: Tmax of LEN | Anytime post dose on Day 1, Day 2 and at either Week 12 or Week 18 | Tmax is defined as the time (observed time point) of Cmax. |
| Cohort 2: PK Parameter: Ctau of LEN | Anytime post dose at either Week 12 or Week 18 | Ctau was defined as the observed drug concentration at the end of the dosing interval. |
| Change From Baseline in CD4+ Cell Count at Week 48 | Baseline and Week 48 | — |
| Cohort 2: PK Parameter: AUCtau of LEN | Anytime post dose at either Week 12 or Week 18 | AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). |
Countries
United States
Contacts
STUDY_DIRECTORGilead Study Director
Gilead Sciences
Participant flow
Recruitment details
Participants were enrolled at study sites in the United States. This is the primary results analysis including data up to Week 48 for the outcome measures. As Cohort 1 never reached Week 48, so, the data for some outcome measures for applicable timepoints up to Week 48 were reported for Cohort 2 only.
Pre-assignment details
322 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1- Group 1 (ISL+LEN) Participants received islatravir (ISL) 40 mg and lenacapavir (LEN) 600 mg orally on Days 1 and 2 and ISL 20 mg and LEN 300 mg orally weekly thereafter from Day 8. They were to take treatment up to at least Week 48, however, all participants were off study treatment prior to Week 12 in the study. | 24 |
| Cohort 1- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg, orally, once daily. They were to take treatment up to Week 48, however, all participants were off study treatment prior to Week 12 in the study. | 12 |
| Cohort 2- Group 1 (ISL+LEN) Participants received ISL 2 mg and LEN 600 mg orally on Day 1 and 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks. | 52 |
| Cohort2- Group 2 (B/F/TAF to ISL+LEN) Participants received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily orally for at least 48 weeks. After 48 weeks, participants will switch from B/F/TAF to ISL+LEN and received ISL 2 mg and LEN 600 mg orally on Day 1 and Day 2, LEN 600 mg orally only on Day 2 and ISL 2 mg and LEN 300 mg orally weekly thereafter from Day 8 for at least 48 weeks. | 52 |
| Total | 140 |
Baseline characteristics
| Characteristic | Cohort 1- Group 1 (ISL+LEN) | Cohort 1- Group 2 (B/F/TAF to ISL+LEN) | Cohort 2- Group 1 (ISL+LEN) | Cohort2- Group 2 (B/F/TAF to ISL+LEN) | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 0 Participants | 2 Participants | 6 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants | 12 Participants | 50 Participants | 46 Participants | 130 Participants |
| Age, Continuous | 42 years STANDARD_DEVIATION 11.9 | 40 years STANDARD_DEVIATION 11.2 | 43 years STANDARD_DEVIATION 12.1 | 45 years STANDARD_DEVIATION 13.3 | 43 years STANDARD_DEVIATION 12.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 4 Participants | 13 Participants | 17 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 8 Participants | 39 Participants | 35 Participants | 99 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 13 Participants | 5 Participants | 21 Participants | 16 Participants | 55 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other or More Than One Race | 1 Participants | 0 Participants | 3 Participants | 5 Participants | 9 Participants |
| Race/Ethnicity, Customized White | 10 Participants | 6 Participants | 25 Participants | 27 Participants | 68 Participants |
| Region of Enrollment United States | 24 Participants | 12 Participants | 52 Participants | 52 Participants | 140 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 10 Participants | 9 Participants | 22 Participants |
| Sex: Female, Male Male | 22 Participants | 11 Participants | 42 Participants | 43 Participants | 118 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 12 | 0 / 53 | 0 / 53 |
| other Total, other adverse events | 11 / 24 | 7 / 12 | 27 / 52 | 29 / 52 |
| serious Total, serious adverse events | 0 / 24 | 0 / 12 | 3 / 52 | 0 / 52 |
Outcome results
Primary
Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 24 as Determined by the US Food and Drug Administration (FDA)-Defined Snapshot Algorithm
The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with the applicable study drug discontinuation status. Week 24 window was between Day 148 and 189 (inclusive). Percentages were rounded off.
Time frame: Week 24
Population: The Full Analysis Set included all randomized participants who took at least 1 dose of study drug. As none of the participants reached Week 24 timepoint in Cohort 1, data for Cohort 1 were not available for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2- Group 1 (ISL+LEN) | Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 24 as Determined by the US Food and Drug Administration (FDA)-Defined Snapshot Algorithm | 1.9 percentage of participants |
| Cohort2- Group 2 (B/F/TAF to ISL+LEN) | Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 24 as Determined by the US Food and Drug Administration (FDA)-Defined Snapshot Algorithm | 0 percentage of participants |
Secondary
Change From Baseline in CD4+ Cell Count at Week 24
Time frame: Baseline and Week 24
Population: The participants in the Safety Analysis Set with available data were analyzed. As none of the participants reached Week 24 timepoint in Cohort 1, data for Cohort 1 were not available for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2- Group 1 (ISL+LEN) | Change From Baseline in CD4+ Cell Count at Week 24 | -4 cells/µL | Standard Deviation 182.1 |
| Cohort2- Group 2 (B/F/TAF to ISL+LEN) | Change From Baseline in CD4+ Cell Count at Week 24 | -57 cells/µL | Standard Deviation 204.2 |
p-value: 0.347795% CI: [-37, 103]ANCOVA
Secondary
Change From Baseline in CD4+ Cell Count at Week 48
Time frame: Baseline and Week 48
Population: The participants in the Safety Analysis Set with available data were analyzed. As none of the participants reached Week 48 timepoint in Cohort 1, data for Cohort 1 were not available for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2- Group 1 (ISL+LEN) | Change From Baseline in CD4+ Cell Count at Week 48 | -12 cells/µL | Standard Deviation 214.7 |
| Cohort2- Group 2 (B/F/TAF to ISL+LEN) | Change From Baseline in CD4+ Cell Count at Week 48 | -29 cells/µL | Standard Deviation 186.1 |
p-value: 0.884995% CI: [-76, 66]ANCOVA
Secondary
Change From Baseline in Clusters of Differentiation 4 (CD4)+ Cell Count at Week 12
Time frame: Baseline and Week 12
Population: The participants from the Safety Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1- Group 1 (ISL+LEN) | Change From Baseline in Clusters of Differentiation 4 (CD4)+ Cell Count at Week 12 | Baseline | 721 cells/µL | Standard Deviation 265 |
| Cohort 1- Group 1 (ISL+LEN) | Change From Baseline in Clusters of Differentiation 4 (CD4)+ Cell Count at Week 12 | Change at Week 12 | -50 cells/µL | Standard Deviation 183 |
| Cohort 1- Group 2 (B/F/TAF to ISL+LEN) | Change From Baseline in Clusters of Differentiation 4 (CD4)+ Cell Count at Week 12 | Change at Week 12 | 18 cells/µL | Standard Deviation 142.3 |
| Cohort 1- Group 2 (B/F/TAF to ISL+LEN) | Change From Baseline in Clusters of Differentiation 4 (CD4)+ Cell Count at Week 12 | Baseline | 659 cells/µL | Standard Deviation 304.8 |
| Cohort 2- Group 1 (ISL+LEN) | Change From Baseline in Clusters of Differentiation 4 (CD4)+ Cell Count at Week 12 | Baseline | 755 cells/µL | Standard Deviation 223.6 |
| Cohort 2- Group 1 (ISL+LEN) | Change From Baseline in Clusters of Differentiation 4 (CD4)+ Cell Count at Week 12 | Change at Week 12 | -23 cells/µL | Standard Deviation 185.6 |
| Cohort2- Group 2 (B/F/TAF to ISL+LEN) | Change From Baseline in Clusters of Differentiation 4 (CD4)+ Cell Count at Week 12 | Baseline | 818 cells/µL | Standard Deviation 271.3 |
| Cohort2- Group 2 (B/F/TAF to ISL+LEN) | Change From Baseline in Clusters of Differentiation 4 (CD4)+ Cell Count at Week 12 | Change at Week 12 | -49 cells/µL | Standard Deviation 180 |
p-value: 0.385995% CI: [-226, 91]ANOVA
p-value: 0.708595% CI: [-56, 82]ANCOVA
Secondary
Cohort 1: Plasma Concentrations for ISL
Time frame: Anytime postdose at Week 4
Population: The Pharmacokinetic (PK) Analysis Set for Cohort 1 included all randomized participants who took at least 1 dose of study drug and have at least 1 nonmissing concentration value reported by the PK laboratory.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1- Group 1 (ISL+LEN) | Cohort 1: Plasma Concentrations for ISL | 42.1 ng/mL | Standard Deviation 49.6 |
Secondary
Cohort 2: Pharmacokinetic (PK) Parameter: Cmax of Islatravir (ISL)
Cmax was defined as the maximum observed concentration of drug.
Time frame: Anytime post dose on Day 1 and at either Week 12 or Week 18
Population: The Pharmacokinetic (PK) Substudy Analysis Set for Cohort 2 included all randomized participants who received at least 1 dose of the study drug, participated in the PK substudy, and had at least 1 nonmissing postdose concentration with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1- Group 1 (ISL+LEN) | Cohort 2: Pharmacokinetic (PK) Parameter: Cmax of Islatravir (ISL) | Day 1 | 19.6 ng/mL | Standard Deviation 6.55 |
| Cohort 1- Group 1 (ISL+LEN) | Cohort 2: Pharmacokinetic (PK) Parameter: Cmax of Islatravir (ISL) | Week 12 or Week 18 | 18.7 ng/mL | Standard Deviation 7.6 |
Secondary
Cohort 2: Pharmacokinetic (PK) Parameter: Cmax of LEN
Cmax was defined as the maximum observed concentration of drug.
Time frame: Anytime post dose on Day 1, Day 2 and at either Week 12 or 18
Population: The participants in Pharmacokinetic Substudy Analysis Set for Cohort 2 with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1- Group 1 (ISL+LEN) | Cohort 2: Pharmacokinetic (PK) Parameter: Cmax of LEN | Day 1 | 46.4 ng/mL | Standard Deviation 29 |
| Cohort 1- Group 1 (ISL+LEN) | Cohort 2: Pharmacokinetic (PK) Parameter: Cmax of LEN | Day 2 | 183 ng/mL | Standard Deviation 189 |
| Cohort 1- Group 1 (ISL+LEN) | Cohort 2: Pharmacokinetic (PK) Parameter: Cmax of LEN | Week 12 or Week 18 | 97.4 ng/mL | Standard Deviation 73.2 |
Secondary
Cohort 2: PK Parameter: AUCtau of ISL
AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Time frame: Anytime post dose at either Week 12 or Week 18
Population: The participants in the Pharmacokinetic Substudy Analysis Set for Cohort 2 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1- Group 1 (ISL+LEN) | Cohort 2: PK Parameter: AUCtau of ISL | 132 h*ng/mL | Standard Deviation 98.1 |
Secondary
Cohort 2: PK Parameter: AUCtau of LEN
AUCtau was defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Time frame: Anytime post dose at either Week 12 or Week 18
Population: The participants in the Pharmacokinetic Substudy Analysis Set for Cohort 2 with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1- Group 1 (ISL+LEN) | Cohort 2: PK Parameter: AUCtau of LEN | 10000 h*ng/mL | Standard Deviation 7440 |
Secondary
Cohort 2: PK Parameter: Ctau of ISL
Ctau was defined as the observed drug concentration at the end of the dosing interval.
Time frame: Anytime post dose at either Week 12 or Week 18
Population: The participants in the Pharmacokinetic Substudy Analysis Set for Cohort 2 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1- Group 1 (ISL+LEN) | Cohort 2: PK Parameter: Ctau of ISL | 0.169 ng/mL | Standard Deviation 0.094 |
Secondary
Cohort 2: PK Parameter: Ctau of LEN
Ctau was defined as the observed drug concentration at the end of the dosing interval.
Time frame: Anytime post dose at either Week 12 or Week 18
Population: The participants in the Pharmacokinetic Substudy Analysis Set for Cohort 2 with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1- Group 1 (ISL+LEN) | Cohort 2: PK Parameter: Ctau of LEN | 36.6 ng/mL | Standard Deviation 22.5 |
Secondary
Cohort 2: PK Parameter: Tmax of ISL
Tmax was defined as the time (observed time point) of Cmax.
Time frame: Anytime post dose on Day 1 and at either Week 12 or Week 18
Population: The participants in the Pharmacokinetic Substudy Analysis Set for Cohort 2 with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1- Group 1 (ISL+LEN) | Cohort 2: PK Parameter: Tmax of ISL | Day 1 | 1.12 hours | Standard Deviation 1.03 |
| Cohort 1- Group 1 (ISL+LEN) | Cohort 2: PK Parameter: Tmax of ISL | Week 12 or Week 18 | 0.793 hours | Standard Deviation 0.423 |
Secondary
Cohort 2: PK Parameter: Tmax of LEN
Tmax is defined as the time (observed time point) of Cmax.
Time frame: Anytime post dose on Day 1, Day 2 and at either Week 12 or Week 18
Population: The participants in the Pharmacokinetic Substudy Analysis Set for Cohort 2 with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1- Group 1 (ISL+LEN) | Cohort 2: PK Parameter: Tmax of LEN | Day 2 | 6.61 hours | Standard Deviation 1.47 |
| Cohort 1- Group 1 (ISL+LEN) | Cohort 2: PK Parameter: Tmax of LEN | Day 1 | 11.4 hours | Standard Deviation 8.96 |
| Cohort 1- Group 1 (ISL+LEN) | Cohort 2: PK Parameter: Tmax of LEN | Week 12 or Week 18 | 5.43 hours | Standard Deviation 1.63 |
Secondary
Percentage of Participants Experiencing Treatment-Emergent Adverse Events Leading to Study Drug Discontinuation
TEAEs were defined as 1 or both of any AEs leading to premature discontinuation of study drug, or any AEs with an onset date on or after the study drug start date and no later than the last exposure date after permanent discontinuation of the study drug. Percentages were rounded off.
Time frame: Up to 5 years
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm
The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 12 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with the applicable study drug discontinuation status. Week 12 window was between Day 71 and 105 (inclusive). Percentages were rounded off.
Time frame: Week 12
Population: The participants in the Full Analysis Set were analyzed. As none of the participants were on-treatment in Cohort 1 at Week 12 (required for the analysis of HIV RNA levels using US FDA-defined Snapshot Algorithm), this outcome measure for Cohort 1 could not be analyzed using US FDA-defined Snapshot Algorithm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2- Group 1 (ISL+LEN) | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm | 98.1 percentage of participants |
| Cohort2- Group 2 (B/F/TAF to ISL+LEN) | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm | 96.2 percentage of participants |
95% CI: [-6.8, 11.6]
Secondary
Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm
The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 12 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with the applicable study drug discontinuation status. Week 12 window was between Day 71 and 105 (inclusive). Percentages were rounded off.
Time frame: Week 12
Population: The participants in the Full Analysis Set were analyzed. As none of the participants were on-treatment in Cohort 1 at Week 12 (required for the analysis of HIV RNA levels using US FDA-defined Snapshot Algorithm), this outcome measure for Cohort 1 could not be analyzed using US FDA-defined Snapshot Algorithm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2- Group 1 (ISL+LEN) | Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm | 1.9 percentage of participants |
| Cohort2- Group 2 (B/F/TAF to ISL+LEN) | Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm | 0 percentage of participants |
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Determined by the US FDA-defined Snapshot Algorithm
The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with the applicable study drug discontinuation status. Week 24 window was between Day 148 and 189 (inclusive). Percentages were rounded off.
Time frame: Week 24
Population: The participants in the Full Analysis Set were analyzed. As none of the participants reached Week 24 timepoint in Cohort 1, data for Cohort 1 were not available for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2- Group 1 (ISL+LEN) | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Determined by the US FDA-defined Snapshot Algorithm | 94.2 percentage of participants |
| Cohort2- Group 2 (B/F/TAF to ISL+LEN) | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Determined by the US FDA-defined Snapshot Algorithm | 96.2 percentage of participants |
95% CI: [-12.4, 8.6]
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm
The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with the applicable study drug discontinuation status. Week 48 window was between Day 316 and 378 (inclusive). Percentages were rounded off.
Time frame: Week 48
Population: The participants in the Full Analysis Set were analyzed. As none of the participants reached Week 48 timepoint in Cohort 1, data for Cohort 1 were not available for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2- Group 1 (ISL+LEN) | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm | 96.2 percentage of participants |
| Cohort2- Group 2 (B/F/TAF to ISL+LEN) | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm | 94.2 percentage of participants |
95% CI: [-8.6, 12.4]
Secondary
Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm
The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with the applicable study drug discontinuation status. Week 48 window was between Day 316 and 378 (inclusive). Percentages were rounded off.
Time frame: Week 48
Population: The participants in the Full Analysis Set were analyzed. As none of the participants reached Week 48 timepoint in Cohort 1, data for Cohort 1 were not available for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2- Group 1 (ISL+LEN) | Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm | 0 percentage of participants |
| Cohort2- Group 2 (B/F/TAF to ISL+LEN) | Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm | 0 percentage of participants |
Secondary
Plasma Concentrations for LEN
Time frame: Anytime postdose at Week 4
Population: The participants in the Pharmacokinetic Analysis Set for Cohort 1 were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1- Group 1 (ISL+LEN) | Plasma Concentrations for LEN | 62.0 ng/mL | Standard Deviation 43.9 |