HIV-1
Conditions
Keywords
emtricitabine, FTC, tenofovir, TDF, antiretroviral, adolescents, children, pediatric, TAF
Brief summary
The primary objective of this study is to confirm the TAF dose and to evaluate the pharmacokinetics (PK) of TAF, safety, and tolerability of F/TAF in children and adolescents with HIV-1 who are virologically suppressed (defined as having \< 50 copies/mL of HIV-1 ribonucleic acid (RNA) for a period of at least 6 months) while on a stable 2 NRTI containing regimen.
Detailed description
A minimum of 100 participants in total (across all cohorts) aged 1 month to \<18 years of age will be enrolled to receive F/TAF. The study will proceed in sequential cohorts as follows: Cohort 1 will switch their current 2-NRTI-containing regimen to F/TAF while continuing on their 3rd ARV agent through 48 weeks; Cohorts 2, 3, and 4 must be on a boosted protease inhibitor (PI) (Cohort 2 only) or any other 3rd ARV agent and will switch their current 2-NRTI-containing regimen to F/TAF while continuing their boosted PI or 3rd ARV agent through 48 weeks. A minimum of 10 participants each in Groups 1 and 2 of Cohort 2, and Cohorts 3 and 4, who are on boosted-ATV as their 3rd ARV agent will be enrolled. Cohorts 2, 3, and 4 will be enrolled by cohort into a two-part study (Parts A and B). After completion of 48 weeks, all participants will be given the option to participate in an extension phase of the study. Gilead will provide F/TAF until a) The participant turns 18 years old and F/TAF is commercially available for use in adults in the country in which the participant is enrolled or b), F/TAF becomes commercially available for pediatric use in the country in which the participant is enrolled or c), Gilead Sciences elects to terminate development of F/TAF in the applicable country. However, Cohort 2 (Part B), Cohorts 3 and 4 were not conducted as planned.
Interventions
DRUGBoosted PIs
Allowed boosted PIs: LPV, ATV, DRV.
DRUGF/TAF
F/TAF tablets administered orally once daily
DRUG3rd ARV agent
A 3rd antiretroviral (ARV) agent may include one of the following: allowed boosted 3rd ARV agents: lopinavir (LPV), atazanavir (ATV), darunavir (DRV); Allowed unboosted 3rd ARV agents: efavirenz (EFV), raltegravir (RAL), dolutegravir (DTG), or nevirapine (NVP)
Sponsors
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Months to 17 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Human immunodeficiency virus 1 (HIV-1) infected male and female adolescents and children aged 1 month to \< 18 years at baseline/Day 1 (according to requirements of the enrolling cohort) * Must be able to give written assent prior to any screening evaluations * Parent or guardian able to give written informed consent prior to any screening evaluations and willing to comply with study requirements * Body weight at screening as follows: * Cohort 1: ≥ 35 kg * Cohort 2, Group 1: ≥ 25 kg * Cohort 2, Group 2: 17 kg to \< 25 kg * Cohort 3: to be updated per a protocol amendment * Cohort 4: to be updated per a protocol amendment * Currently on a stable 2-nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) containing regimen that includes a 3rd antiretroviral (ARV) agent for ≥ 6 consecutive months prior to screening * Plasma HIV-1 ribonucleic acid (RNA) levels \< 50 copies/mL for ≥ 6 consecutive months preceding the screening visit * No opportunistic infection within 30 days of study entry (at baseline/Day 1) * A negative serum β-human chorionic gonadotropin (HCG) pregnancy test is required for females of childbearing potential only Key
Exclusion criteria
* An acquired immunodeficiency syndrome (AIDS) - indicator condition with onset within 30 days prior to screening * Life expectancy of \< 2 years * Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline/Day 1 * Evidence of active pulmonary or extra-pulmonary tuberculosis disease within 3 months of the screening visit * Active hepatitis C virus (HCV) infection defined as positive for HCV antibody and having detectable HCV RNA * Positive hepatitis B surface antigen or other evidence of active hepatitis B virus (HBV) infection. * Have any serious or active medical or psychiatric illness which, in the opinion of the Investigator, would interfere with treatment, assessment, or compliance with the protocol. * Pregnant or lactating females * Have history of significant drug sensitivity or drug allergy * Have previously participated in an investigational trial involving administration of any investigational agent, other than TDF, within 30 days prior to the study dosing NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) Parameter (Cohort 1): AUCtau of Tenofovir Alafenamide (TAF) | Any time at Week 2 visit | AUCtau is defined as the area under the drug concentration versus time curve over the dosing interval. |
| PK Parameter (Cohort 2: Part A - Groups 1 and 2): AUCtau of TAF | Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits | AUCtau is defined as the area under the drug concentration versus time curve over the dosing interval. |
| Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Through Week 24 | Baseline through Week 24 | An AE is any untoward medical occurrence in a clinical study participant which does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. The TEAEs were defined as any AEs with an onset date of on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug or any AEs leading to premature discontinuation of study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK Parameter (Cohort 2: Part A - Groups 1 and 2): Clast of TAF | Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits | Clast is defined as the last observable concentration of drug. |
| PK Parameter (Cohort 1): CL/F of TAF | Any time at Week 2 visit | CL/F is defined as the apparent clearance following oral administration of the drug. |
| PK Parameter (Cohort 2: Part A - Groups 1 and 2): CL/F of TAF | Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits | CL/F is defined as the apparent clearance following oral administration of the drug. |
| PK Parameter (Cohort 1): Vz/F of TAF | Any time at Week 2 visit | Vz/F is defined as the apparent volume of distribution of the drug following oral administration. |
| PK Parameter (Cohort 2: Part A - Groups 1 and 2): Vz/F of TAF | Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits | Vz/F is defined as the apparent volume of distribution of the drug following oral administration. |
| PK Parameter (Cohort 1): AUCtau of FTC and TFV | Any time at Week 2 visit | AUCtau is defined as the area under the drug concentration versus time curve over the dosing interval. |
| PK Parameter (Cohort 2: Part A - Groups 1 and 2): AUCtau of FTC and TFV | Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits | AUCtau is defined as the area under the drug concentration versus time curve over the dosing interval. |
| PK Parameter (Cohort 1): Ctau of FTC and TFV | Any time at Week 2 visit | Ctau is defined as the observed drug concentration at the end of the dosing interval. |
| PK Parameter (Cohort 2: Part A - Groups 1 and 2): Ctau of FTC and TFV | Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits | Ctau is defined as the observed drug concentration at the end of the dosing interval. |
| PK Parameter (Cohort 1): Cmax of TAF, FTC, and TFV | Any time at Week 2 visit | Cmax is defined as the maximum concentration of drug. |
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24, as Defined by the United States Food and Drug Administration (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 defined a participant'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 HIV-1 RNA < 50 Copies/mL at Week 48, as Defined 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 defined a participant'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. |
| Change From Baseline in CD4+ Cell Count at Week 24 | Baseline, Week 24 | — |
| Change From Baseline in CD4+ Cell Count at Week 48 | Baseline, Week 48 | — |
| Change From Baseline in CD4 Percentage at Week 24 | Baseline, Week 24 | — |
| Change From Baseline in CD4 Percentage at Week 48 | Baseline, Week 48 | — |
| Number of Participants With Palatability of F/TAF Formulation | Week 2 (for Cohort 1), Week 2 and Week 4 (for Cohort 2) | Palatability was reported based on the pleasant product taste as 'Yes' or 'No'. Data has been reported for Participant Response (PR) and Guardian Response (GR). Participants with missing data were reported as N/A. |
| Number of Participants With Acceptability of F/TAF Formulation | Baseline up to Week 4 | Acceptability has been reported for categories medication size, shape and difficulty swallowing as 'Yes' or 'No' for Participant Response (PR) and Guardian Response (GR). Participants with missing data were reported as N/A. |
| Percentage of Participants Experiencing TEAEs and SAEs Through Week 48 | Baseline through Week 48 | An AE is any untoward medical occurrence in a clinical study participant which does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. The TEAEs were defined as any AEs with an onset date of on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug or any AEs leading to premature discontinuation of study drug. |
| PK Parameter (Cohort 2: Part A - Groups 1 and 2): Cmax of TAF, FTC, and TFV | Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits | Cmax is defined as the maximum concentration of drug. |
| PK Parameter (Cohort 1): Clast of TAF | Any time at Week 2 visit | Clast is defined as the last observable concentration of drug. |
Countries
Panama, South Africa, United States
Participant flow
Recruitment details
49 participants were screened. Participants were enrolled at study sites in Panama, South Africa, and United States.
Pre-assignment details
No participant was enrolled in Cohort 2 (Part B: Groups 1 and 2), and Cohorts 3 and 4 (Parts A and B). Data is reported only for Cohorts 1 and 2 (Part A: Groups 1 and 2). The study had a main treatment phase of 48 weeks and extension phase. It was prespecified to analyze Cohort 1 together as both treatments (F/TAF 200/10 mg with boosted 3rd ARV and F/TAF 200/25 mg with unboosted 3rd ARV) were expected to have a similar effect on efficacy and safety for target population.
Participants by arm
| Arm | Count |
|---|---|
| F/TAF+3rd ARV Agent (Cohort 1) Participants between 12 to \< 18 years of age and ≥ 35 kg body weight received emtricitabine/tenofovir alafenamide (F/TAF) 200/10 mg fixed-dose combination (FDC) tablet (with boosted 3rd antiretroviral \[ARV\] agent) or F/TAF 200/25 mg FDC tablet (with unboosted 3rd ARV agent) orally once daily for 48 weeks. After completion of 48 weeks, all participants were given the option to participate in the extension phase of the study to continue with F/TAF+3rd ARV agent. Gilead provided F/TAF until a) the participant turned 18 and F/TAF was commercially available for use in adults in the country in which the participant was enrolled or, b) F/TAF became commercially available for pediatric use in the country in which the participant was enrolled or, c) Gilead Sciences elected to terminate development of F/TAF in the applicable country. (Allowed boosted 3rd ARV agents: lopinavir \[LPV\], atazanavir \[ATV\], darunavir \[DRV\]; Allowed unboosted 3rd ARV agents: efavirenz \[EFV\], raltegravir \[RAL\], dolutegravir \[DTG\], or nevirapine \[NVP\]). The participants received the study drug up to a maximum of 438.9 weeks. | 28 |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 1) Participants between 6 to \< 12 years of age and ≥ 25 kg body weight received F/TAF 200/25 mg FDC tablet orally once daily while continuing on their boosted protease inhibitor (PI) for 48 weeks. After completion of 48 weeks, all participants were given the option to participate in the extension phase of the study to continue with F/TAF+3rd ARV agent. Gilead provided F/TAF until a) the participant turned 18 and F/TAF was commercially available for use in adults in the country in which the participant was enrolled or, b) F/TAF became commercially available for pediatric use in the country in which the participant was enrolled or, c) Gilead Sciences elected to terminate development of F/TAF in the applicable country. (Allowed boosted PIs: ATV, LPV or DRV). The participants received the study drug up to a maximum of 315.0 weeks. | 9 |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) Participants between 2 to \< 12 years of age and 17 to \< 25 kg body weight received F/TAF 120/15 mg FDC orally once daily while continuing on their 3rd ARV agent for 48 weeks. After completion of 48 weeks, all participants were given the option to participate in the extension phase of the study to continue with F/TAF+3rd ARV agent. Gilead provided F/TAF until a) the participant turned 18 and F/TAF was commercially available for use in adults in the country in which the participant was enrolled or, b) F/TAF became commercially available for pediatric use in the country in which the participant was enrolled or, c) Gilead Sciences elected to terminate development of F/TAF in the applicable country. (Allowed boosted 3rd ARV agents: LPV, ATV, DRV; Allowed unboosted 3rd ARV agents: EFV, RAL, DTG, or NVP). The participants received the study drug up to a maximum of 103.1 weeks. | 3 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Extension Phase | Investigator's Discretion | 0 | 0 | 0 | 14 | 1 | 0 |
| Extension Phase | Lost to Follow-up | 0 | 0 | 0 | 1 | 1 | 0 |
| Extension Phase | Non-compliance with Study Drug | 0 | 0 | 0 | 2 | 0 | 0 |
| Extension Phase | Pregnancy | 0 | 0 | 0 | 1 | 0 | 0 |
| Main Phase | Enrolled but Never Treated | 1 | 0 | 0 | 0 | 0 | 0 |
| Main Phase | Investigator's Discretion | 0 | 2 | 0 | 0 | 0 | 0 |
| Main Phase | Withdrew Consent | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 1) | F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | F/TAF+3rd ARV Agent (Cohort 1) | Total |
|---|---|---|---|---|
| Age, Continuous | 10 years STANDARD_DEVIATION 1 | 7 years STANDARD_DEVIATION 1.2 | 14 years STANDARD_DEVIATION 1.6 | 13 years STANDARD_DEVIATION 2.6 |
| Age, Customized 12 to < 15 years | 0 Participants | 0 Participants | 19 Participants | 19 Participants |
| Age, Customized 15 to < 18 years | 0 Participants | 0 Participants | 9 Participants | 9 Participants |
| Age, Customized 6 to < 12 years | 9 Participants | 3 Participants | 0 Participants | 12 Participants |
| CD4 Percentage (%) | 36.7 percentage of lymphocytes STANDARD_DEVIATION 4.35 | 36.1 percentage of lymphocytes STANDARD_DEVIATION 3.35 | 36.1 percentage of lymphocytes STANDARD_DEVIATION 6.4 | 36.2 percentage of lymphocytes STANDARD_DEVIATION 5.73 |
| Cluster of Differentiation 4 (CD4) Cell Count | 871 cells/µL STANDARD_DEVIATION 364.8 | 1209 cells/µL STANDARD_DEVIATION 306.3 | 909 cells/µL STANDARD_DEVIATION 242.7 | 923 cells/µL STANDARD_DEVIATION 282.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 1 Participants | 14 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 2 Participants | 14 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Human Immunodeficiency Virus, Type 1 Ribonucleic Acid (HIV-1 RNA) < 50 copies/mL | 9 Participants | 3 Participants | 27 Participants | 39 Participants |
| Human Immunodeficiency Virus, Type 1 Ribonucleic Acid (HIV-1 RNA) ≥ 50 copies/mL | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Black | 4 Participants | 2 Participants | 12 Participants | 18 Participants |
| Race/Ethnicity, Customized Race Other | 5 Participants | 1 Participants | 12 Participants | 18 Participants |
| Race/Ethnicity, Customized Race White | 0 Participants | 0 Participants | 3 Participants | 3 Participants |
| Region of Enrollment Panama | 6 participants | 1 participants | 12 participants | 19 participants |
| Region of Enrollment South Africa | 0 participants | 2 participants | 10 participants | 12 participants |
| Region of Enrollment United States | 3 participants | 0 participants | 6 participants | 9 participants |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 12 Participants | 19 Participants |
| Sex: Female, Male Male | 4 Participants | 1 Participants | 16 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 9 | 0 / 3 |
| other Total, other adverse events | 27 / 28 | 8 / 9 | 2 / 3 |
| serious Total, serious adverse events | 4 / 28 | 1 / 9 | 0 / 3 |
Outcome results
Primary
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Through Week 24
An AE is any untoward medical occurrence in a clinical study participant which does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. The TEAEs were defined as any AEs with an onset date of on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug or any AEs leading to premature discontinuation of study drug.
Time frame: Baseline through Week 24
Population: The Safety Analysis Set included all participants who were enrolled in the study and had received at least one dose of study medication. It was prespecified to analyze data from Cohort 1 together because both treatments (F/TAF 200/10 mg with boosted 3rd ARV and F/TAF 200/25 mg with unboosted 3rd ARV) were expected to have a similar effect on the efficacy and safety for the target population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Through Week 24 | Any AEs | 82.1 percentage of participants |
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Through Week 24 | SAEs | 7.1 percentage of participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Through Week 24 | Any AEs | 66.7 percentage of participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Through Week 24 | SAEs | 0 percentage of participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Through Week 24 | Any AEs | 66.7 percentage of participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Through Week 24 | SAEs | 0 percentage of participants |
Primary
Pharmacokinetic (PK) Parameter (Cohort 1): AUCtau of Tenofovir Alafenamide (TAF)
AUCtau is defined as the area under the drug concentration versus time curve over the dosing interval.
Time frame: Any time at Week 2 visit
Population: Participants in the Intensive PK (IPK) Analysis Set (participants who were enrolled in Cohort 1 for IPK evaluation, had received at least one dose of study medication, and had at least 1 non-missing PK concentration data for any analyte of interest (e.g., emtricitabine (FTC), TAF, and tenofovir (TFV))) with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | Pharmacokinetic (PK) Parameter (Cohort 1): AUCtau of Tenofovir Alafenamide (TAF) | 139.9 h*ng/mL | Standard Deviation 113.23 |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Pharmacokinetic (PK) Parameter (Cohort 1): AUCtau of Tenofovir Alafenamide (TAF) | 200.6 h*ng/mL | Standard Deviation 83.8 |
Primary
PK Parameter (Cohort 2: Part A - Groups 1 and 2): AUCtau of TAF
AUCtau is defined as the area under the drug concentration versus time curve over the dosing interval.
Time frame: Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits
Population: The IPK Analysis Set included all participants who were enrolled into the study, had received at least one dose of study medication, and had at least 1 non-missing PK concentration data for any analyte of interest (e.g., FTC, TAF, and TFV).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 2: Part A - Groups 1 and 2): AUCtau of TAF | 210.8 h*ng/mL | Standard Deviation 97.35 |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 2: Part A - Groups 1 and 2): AUCtau of TAF | 220.2 h*ng/mL | Standard Deviation 187.96 |
Secondary
Change From Baseline in CD4+ Cell Count at Week 24
Time frame: Baseline, Week 24
Population: Participants in the Full Analysis Set with available data were analyzed. It was prespecified to analyze data from Cohort 1 together because both treatments (F/TAF 200/10 mg with boosted 3rd ARV and F/TAF 200/25 mg with unboosted 3rd ARV) were expected to have a similar effect on the efficacy and safety for the target population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | Change From Baseline in CD4+ Cell Count at Week 24 | -130 cells/µL | Standard Deviation 272.6 |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Change From Baseline in CD4+ Cell Count at Week 24 | 68 cells/µL | Standard Deviation 352.5 |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Change From Baseline in CD4+ Cell Count at Week 24 | -299 cells/µL | Standard Deviation 48.8 |
Secondary
Change From Baseline in CD4+ Cell Count at Week 48
Time frame: Baseline, Week 48
Population: Participants in the Full Analysis Set with available data were analyzed. It was prespecified to analyze data from Cohort 1 together because both treatments (F/TAF 200/10 mg with boosted 3rd ARV and F/TAF 200/25 mg with unboosted 3rd ARV) were expected to have a similar effect on the efficacy and safety for the target population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | Change From Baseline in CD4+ Cell Count at Week 48 | -105 cells/µL | Standard Deviation 162.9 |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Change From Baseline in CD4+ Cell Count at Week 48 | 210 cells/µL | Standard Deviation 406.5 |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Change From Baseline in CD4+ Cell Count at Week 48 | -124 cells/µL | Standard Deviation 37.5 |
Secondary
Change From Baseline in CD4 Percentage at Week 24
Time frame: Baseline, Week 24
Population: Participants in the Full Analysis Set with available data were analyzed. It was prespecified to analyze data from Cohort 1 together because both treatments (F/TAF 200/10 mg with boosted 3rd ARV and F/TAF 200/25 mg with unboosted 3rd ARV) were expected to have a similar effect on the efficacy and safety for the target population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | Change From Baseline in CD4 Percentage at Week 24 | -0.21 percentage of lymphocytes | Standard Deviation 3.84 |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Change From Baseline in CD4 Percentage at Week 24 | 1.29 percentage of lymphocytes | Standard Deviation 2.395 |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Change From Baseline in CD4 Percentage at Week 24 | 0.60 percentage of lymphocytes | Standard Deviation 5.798 |
Secondary
Change From Baseline in CD4 Percentage at Week 48
Time frame: Baseline, Week 48
Population: Participants in the Full Analysis Set with available data were analyzed. It was prespecified to analyze data from Cohort 1 together because both treatments (F/TAF 200/10 mg with boosted 3rd ARV and F/TAF 200/25 mg with unboosted 3rd ARV) were expected to have a similar effect on the efficacy and safety for the target population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | Change From Baseline in CD4 Percentage at Week 48 | -0.20 percentage of lymphocytes | Standard Deviation 3.407 |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Change From Baseline in CD4 Percentage at Week 48 | 0.70 percentage of lymphocytes | Standard Deviation 3.52 |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Change From Baseline in CD4 Percentage at Week 48 | 3.65 percentage of lymphocytes | Standard Deviation 7.283 |
Secondary
Number of Participants With Acceptability of F/TAF Formulation
Acceptability has been reported for categories medication size, shape and difficulty swallowing as 'Yes' or 'No' for Participant Response (PR) and Guardian Response (GR). Participants with missing data were reported as N/A.
Time frame: Baseline up to Week 4
Population: Participants in the Safety Analysis Set with available data were analyzed. It was prespecified to analyze data from Cohort 1 together because both treatments (F/TAF 200/10 mg with boosted 3rd ARV and F/TAF 200/25 mg with unboosted 3rd ARV) were expected to have a similar effect on the efficacy and safety for the target population.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Acceptability of F/TAF Formulation | Participant Response: Was the Study Medication Size Acceptable? | Yes | 25 Participants |
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Acceptability of F/TAF Formulation | Participant Response: Was the Study Medication Size Acceptable? | N/A | 0 Participants |
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Acceptability of F/TAF Formulation | Participant Response: Was the Study Medication Shape Acceptable? | Yes | 25 Participants |
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Acceptability of F/TAF Formulation | Guardian Response: Did the Participant Have Difficulty Swallowing the Tablet? | N/A | 4 Participants |
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Acceptability of F/TAF Formulation | Guardian Response: Did the Participant Have Difficulty Swallowing the Tablet? | No | 21 Participants |
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Acceptability of F/TAF Formulation | Participant Response: Was the Study Medication Shape Acceptable? | No | 0 Participants |
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Acceptability of F/TAF Formulation | Guardian Response: Did the Participant Have Difficulty Swallowing the Tablet? | Yes | 0 Participants |
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Acceptability of F/TAF Formulation | Participant Response: Was the Study Medication Size Acceptable? | No | 0 Participants |
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Acceptability of F/TAF Formulation | Participant Response: Was the Study Medication Shape Acceptable? | N/A | 0 Participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Acceptability of F/TAF Formulation | Participant Response: Was the Study Medication Size Acceptable? | N/A | 0 Participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Acceptability of F/TAF Formulation | Participant Response: Was the Study Medication Size Acceptable? | No | 0 Participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Acceptability of F/TAF Formulation | Guardian Response: Did the Participant Have Difficulty Swallowing the Tablet? | No | 9 Participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Acceptability of F/TAF Formulation | Guardian Response: Did the Participant Have Difficulty Swallowing the Tablet? | N/A | 0 Participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Acceptability of F/TAF Formulation | Participant Response: Was the Study Medication Shape Acceptable? | N/A | 0 Participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Acceptability of F/TAF Formulation | Participant Response: Was the Study Medication Size Acceptable? | Yes | 9 Participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Acceptability of F/TAF Formulation | Participant Response: Was the Study Medication Shape Acceptable? | Yes | 9 Participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Acceptability of F/TAF Formulation | Guardian Response: Did the Participant Have Difficulty Swallowing the Tablet? | Yes | 0 Participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Acceptability of F/TAF Formulation | Participant Response: Was the Study Medication Shape Acceptable? | No | 0 Participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Number of Participants With Acceptability of F/TAF Formulation | Guardian Response: Did the Participant Have Difficulty Swallowing the Tablet? | N/A | 1 Participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Number of Participants With Acceptability of F/TAF Formulation | Participant Response: Was the Study Medication Size Acceptable? | Yes | 3 Participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Number of Participants With Acceptability of F/TAF Formulation | Participant Response: Was the Study Medication Size Acceptable? | No | 0 Participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Number of Participants With Acceptability of F/TAF Formulation | Participant Response: Was the Study Medication Size Acceptable? | N/A | 0 Participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Number of Participants With Acceptability of F/TAF Formulation | Participant Response: Was the Study Medication Shape Acceptable? | Yes | 3 Participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Number of Participants With Acceptability of F/TAF Formulation | Participant Response: Was the Study Medication Shape Acceptable? | No | 0 Participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Number of Participants With Acceptability of F/TAF Formulation | Participant Response: Was the Study Medication Shape Acceptable? | N/A | 0 Participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Number of Participants With Acceptability of F/TAF Formulation | Guardian Response: Did the Participant Have Difficulty Swallowing the Tablet? | Yes | 0 Participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Number of Participants With Acceptability of F/TAF Formulation | Guardian Response: Did the Participant Have Difficulty Swallowing the Tablet? | No | 2 Participants |
Secondary
Number of Participants With Palatability of F/TAF Formulation
Palatability was reported based on the pleasant product taste as 'Yes' or 'No'. Data has been reported for Participant Response (PR) and Guardian Response (GR). Participants with missing data were reported as N/A.
Time frame: Week 2 (for Cohort 1), Week 2 and Week 4 (for Cohort 2)
Population: Participants in the Safety Analysis Set were analyzed. It was prespecified to analyze data from Cohort 1 together because both treatments (F/TAF 200/10 mg with boosted 3rd ARV and F/TAF 200/25 mg with unboosted 3rd ARV) were expected to have a similar effect on the efficacy and safety for the target population.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Palatability of F/TAF Formulation | Week 2: Participant Response: Was the Study Drug Palatable? | No | 0 Participants |
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Palatability of F/TAF Formulation | Week 2: Guardian Response: Did the Participant Complain of the Taste of the Tablet? | No | 12 Participants |
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Palatability of F/TAF Formulation | Week 2: Participant Response: Was the Study Drug Palatable? | NA | 3 Participants |
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Palatability of F/TAF Formulation | Week 2: Guardian Response: Did the Participant Complain of the Taste of the Tablet? | NA | 16 Participants |
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Palatability of F/TAF Formulation | Week 2: Guardian Response: Was the Study Drug Palatable to the Participant? | Yes | 11 Participants |
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Palatability of F/TAF Formulation | Week 2: Guardian Response: Did the Participant Complain of the Taste of the Tablet? | Yes | 0 Participants |
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Palatability of F/TAF Formulation | Week 2: Participant Response: Was the Study Drug Palatable? | Yes | 25 Participants |
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Palatability of F/TAF Formulation | Week 2: Guardian Response: Was the Study Drug Palatable to the Participant? | NA | 17 Participants |
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Palatability of F/TAF Formulation | Week 2: Guardian Response: Was the Study Drug Palatable to the Participant? | No | 0 Participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Palatability of F/TAF Formulation | Week 2: Guardian Response: Was the Study Drug Palatable to the Participant? | Yes | 9 Participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Palatability of F/TAF Formulation | Week 2: Guardian Response: Did the Participant Complain of the Taste of the Tablet? | NA | 0 Participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Palatability of F/TAF Formulation | Week 2: Participant Response: Was the Study Drug Palatable? | NA | 0 Participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Palatability of F/TAF Formulation | Week 4: Guardian Response: Did the Participant Complain of the Taste of the Tablet? | Yes | 0 Participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Palatability of F/TAF Formulation | Week 2: Participant Response: Was the Study Drug Palatable? | Yes | 9 Participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Palatability of F/TAF Formulation | Week 4: Guardian Response: Did the Participant Complain of the Taste of the Tablet? | No | 9 Participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Palatability of F/TAF Formulation | Week 4: Participant Response: Was the Study Drug Palatable? | Yes | 9 Participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Palatability of F/TAF Formulation | Week 4: Guardian Response: Did the Participant Complain of the Taste of the Tablet? | NA | 0 Participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Palatability of F/TAF Formulation | Week 4: Guardian Response: Was the Study Drug Palatable to the Participant? | Yes | 9 Participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Palatability of F/TAF Formulation | Week 4: Participant Response: Was the Study Drug Palatable? | No | 0 Participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Palatability of F/TAF Formulation | Week 4: Guardian Response: Was the Study Drug Palatable to the Participant? | No | 0 Participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Palatability of F/TAF Formulation | Week 2: Participant Response: Was the Study Drug Palatable? | No | 0 Participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Palatability of F/TAF Formulation | Week 4: Guardian Response: Was the Study Drug Palatable to the Participant? | NA | 0 Participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Palatability of F/TAF Formulation | Week 2: Guardian Response: Did the Participant Complain of the Taste of the Tablet? | Yes | 0 Participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Palatability of F/TAF Formulation | Week 2: Guardian Response: Was the Study Drug Palatable to the Participant? | No | 0 Participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Palatability of F/TAF Formulation | Week 2: Guardian Response: Was the Study Drug Palatable to the Participant? | NA | 0 Participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Palatability of F/TAF Formulation | Week 2: Guardian Response: Did the Participant Complain of the Taste of the Tablet? | No | 9 Participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Number of Participants With Palatability of F/TAF Formulation | Week 4: Participant Response: Was the Study Drug Palatable? | NA | 0 Participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Number of Participants With Palatability of F/TAF Formulation | Week 4: Guardian Response: Was the Study Drug Palatable to the Participant? | Yes | 1 Participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Number of Participants With Palatability of F/TAF Formulation | Week 2: Guardian Response: Was the Study Drug Palatable to the Participant? | Yes | 1 Participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Number of Participants With Palatability of F/TAF Formulation | Week 4: Guardian Response: Was the Study Drug Palatable to the Participant? | NA | 2 Participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Number of Participants With Palatability of F/TAF Formulation | Week 2: Participant Response: Was the Study Drug Palatable? | Yes | 2 Participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Number of Participants With Palatability of F/TAF Formulation | Week 2: Participant Response: Was the Study Drug Palatable? | No | 0 Participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Number of Participants With Palatability of F/TAF Formulation | Week 2: Participant Response: Was the Study Drug Palatable? | NA | 1 Participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Number of Participants With Palatability of F/TAF Formulation | Week 4: Participant Response: Was the Study Drug Palatable? | Yes | 3 Participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Number of Participants With Palatability of F/TAF Formulation | Week 4: Participant Response: Was the Study Drug Palatable? | No | 0 Participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Number of Participants With Palatability of F/TAF Formulation | Week 2: Guardian Response: Was the Study Drug Palatable to the Participant? | No | 0 Participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Number of Participants With Palatability of F/TAF Formulation | Week 2: Guardian Response: Was the Study Drug Palatable to the Participant? | NA | 2 Participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Number of Participants With Palatability of F/TAF Formulation | Week 4: Participant Response: Was the Study Drug Palatable? | NA | 0 Participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Number of Participants With Palatability of F/TAF Formulation | Week 4: Guardian Response: Was the Study Drug Palatable to the Participant? | No | 0 Participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Number of Participants With Palatability of F/TAF Formulation | Week 2: Guardian Response: Did the Participant Complain of the Taste of the Tablet? | Yes | 0 Participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Number of Participants With Palatability of F/TAF Formulation | Week 2: Guardian Response: Did the Participant Complain of the Taste of the Tablet? | No | 1 Participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Number of Participants With Palatability of F/TAF Formulation | Week 2: Guardian Response: Did the Participant Complain of the Taste of the Tablet? | NA | 2 Participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Number of Participants With Palatability of F/TAF Formulation | Week 4: Guardian Response: Did the Participant Complain of the Taste of the Tablet? | Yes | 0 Participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Number of Participants With Palatability of F/TAF Formulation | Week 4: Guardian Response: Did the Participant Complain of the Taste of the Tablet? | No | 1 Participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Number of Participants With Palatability of F/TAF Formulation | Week 4: Guardian Response: Did the Participant Complain of the Taste of the Tablet? | NA | 2 Participants |
Secondary
Percentage of Participants Experiencing TEAEs and SAEs Through Week 48
An AE is any untoward medical occurrence in a clinical study participant which does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. The TEAEs were defined as any AEs with an onset date of on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug or any AEs leading to premature discontinuation of study drug.
Time frame: Baseline through Week 48
Population: Participants in the Safety Analysis Set were analyzed. It was prespecified to analyze data from Cohort 1 together because both treatments (F/TAF 200/10 mg with boosted 3rd ARV and F/TAF 200/25 mg with unboosted 3rd ARV) were expected to have a similar effect on the efficacy and safety for the target population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | Percentage of Participants Experiencing TEAEs and SAEs Through Week 48 | Any AEs | 89.3 percentage of participants |
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | Percentage of Participants Experiencing TEAEs and SAEs Through Week 48 | SAEs | 7.1 percentage of participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Percentage of Participants Experiencing TEAEs and SAEs Through Week 48 | Any AEs | 77.8 percentage of participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Percentage of Participants Experiencing TEAEs and SAEs Through Week 48 | SAEs | 0 percentage of participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Percentage of Participants Experiencing TEAEs and SAEs Through Week 48 | Any AEs | 66.7 percentage of participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Percentage of Participants Experiencing TEAEs and SAEs Through Week 48 | SAEs | 0 percentage of participants |
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24, as Defined by the United States Food and Drug Administration (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 defined a participant'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: The Full Analysis Set included all participants who were enrolled in the study and had received at least one dose of study medication. It was prespecified to analyze data from Cohort 1 together because both treatments (F/TAF 200/10 mg with boosted 3rd ARV and F/TAF 200/25 mg with unboosted 3rd ARV) were expected to have a similar effect on the efficacy and safety for the target population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24, as Defined by the United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm | 92.9 percentage of participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24, as Defined by the United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm | 100.0 percentage of participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24, as Defined by the United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm | 66.7 percentage of participants |
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48, as Defined 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 defined a participant'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: Participants in the Full Analysis Set were analyzed. It was prespecified to analyze data from Cohort 1 together because both treatments (F/TAF 200/10 mg with boosted 3rd ARV and F/TAF 200/25 mg with unboosted 3rd ARV) were expected to have a similar effect on the efficacy and safety for the target population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48, as Defined by the US FDA-Defined Snapshot Algorithm | 89.3 percentage of participants |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48, as Defined by the US FDA-Defined Snapshot Algorithm | 77.8 percentage of participants |
| F/TAF+3rd ARV Agent (Cohort 2, Part A - Group 2) | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48, as Defined by the US FDA-Defined Snapshot Algorithm | 66.7 percentage of participants |
Secondary
PK Parameter (Cohort 1): AUCtau of FTC and TFV
AUCtau is defined as the area under the drug concentration versus time curve over the dosing interval.
Time frame: Any time at Week 2 visit
Population: Participants in the IPK Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 1): AUCtau of FTC and TFV | AUCtau of FTC | 14769.9 h*ng/mL | Standard Deviation 4481.23 |
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 1): AUCtau of FTC and TFV | AUCtau of TFV | 415.5 h*ng/mL | Standard Deviation 105.92 |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 1): AUCtau of FTC and TFV | AUCtau of FTC | 14339.8 h*ng/mL | Standard Deviation 6099.55 |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 1): AUCtau of FTC and TFV | AUCtau of TFV | 193.2 h*ng/mL | Standard Deviation 46.73 |
Secondary
PK Parameter (Cohort 1): Clast of TAF
Clast is defined as the last observable concentration of drug.
Time frame: Any time at Week 2 visit
Population: Participants in the IPK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 1): Clast of TAF | 2.2 ng/mL | Standard Deviation 0.98 |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 1): Clast of TAF | 5.5 ng/mL | Standard Deviation 3.76 |
Secondary
PK Parameter (Cohort 1): CL/F of TAF
CL/F is defined as the apparent clearance following oral administration of the drug.
Time frame: Any time at Week 2 visit
Population: Participants in the IPK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 1): CL/F of TAF | 129.8 L/hr | Standard Deviation 101.67 |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 1): CL/F of TAF | 143.4 L/hr | Standard Deviation 53.55 |
Secondary
PK Parameter (Cohort 1): Cmax of TAF, FTC, and TFV
Cmax is defined as the maximum concentration of drug.
Time frame: Any time at Week 2 visit
Population: Participants in the IPK Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 1): Cmax of TAF, FTC, and TFV | Cmax of TAF | 89.1 ng/mL | Standard Deviation 77.63 |
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 1): Cmax of TAF, FTC, and TFV | Cmax of FTC | 2259.2 ng/mL | Standard Deviation 470.75 |
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 1): Cmax of TAF, FTC, and TFV | Cmax of TFV | 21.2 ng/mL | Standard Deviation 4.89 |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 1): Cmax of TAF, FTC, and TFV | Cmax of TAF | 139.3 ng/mL | Standard Deviation 76.17 |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 1): Cmax of TAF, FTC, and TFV | Cmax of FTC | 2320.0 ng/mL | Standard Deviation 482.18 |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 1): Cmax of TAF, FTC, and TFV | Cmax of TFV | 11.6 ng/mL | Standard Deviation 2.74 |
Secondary
PK Parameter (Cohort 1): Ctau of FTC and TFV
Ctau is defined as the observed drug concentration at the end of the dosing interval.
Time frame: Any time at Week 2 visit
Population: Participants in the IPK Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 1): Ctau of FTC and TFV | Ctau of FTC | 223.4 ng/mL | Standard Deviation 482.59 |
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 1): Ctau of FTC and TFV | Ctau of TFV | 15.7 ng/mL | Standard Deviation 4.11 |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 1): Ctau of FTC and TFV | Ctau of FTC | 301.7 ng/mL | Standard Deviation 624.77 |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 1): Ctau of FTC and TFV | Ctau of TFV | 6.7 ng/mL | Standard Deviation 3 |
Secondary
PK Parameter (Cohort 1): Vz/F of TAF
Vz/F is defined as the apparent volume of distribution of the drug following oral administration.
Time frame: Any time at Week 2 visit
Population: Participants in the IPK Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 1): Vz/F of TAF | 87.3 liters | Standard Deviation 60.68 |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 1): Vz/F of TAF | 95.3 liters | Standard Deviation 43.47 |
Secondary
PK Parameter (Cohort 2: Part A - Groups 1 and 2): AUCtau of FTC and TFV
AUCtau is defined as the area under the drug concentration versus time curve over the dosing interval.
Time frame: Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits
Population: Participants in the IPK Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 2: Part A - Groups 1 and 2): AUCtau of FTC and TFV | AUCtau of FTC | 12360.8 h*ng/mL | Standard Deviation 2928.36 |
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 2: Part A - Groups 1 and 2): AUCtau of FTC and TFV | AUCtau of TFV | 999.4 h*ng/mL | Standard Deviation 409.33 |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 2: Part A - Groups 1 and 2): AUCtau of FTC and TFV | AUCtau of FTC | 11171.7 h*ng/mL | Standard Deviation 2921.64 |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 2: Part A - Groups 1 and 2): AUCtau of FTC and TFV | AUCtau of TFV | 908.2 h*ng/mL | Standard Deviation 90.62 |
Secondary
PK Parameter (Cohort 2: Part A - Groups 1 and 2): Clast of TAF
Clast is defined as the last observable concentration of drug.
Time frame: Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits
Population: Participants in the IPK Analysis Set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 2: Part A - Groups 1 and 2): Clast of TAF | 2.9 ng/mL | Standard Deviation 2.32 |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 2: Part A - Groups 1 and 2): Clast of TAF | 2.1 ng/mL | Standard Deviation 0.86 |
Secondary
PK Parameter (Cohort 2: Part A - Groups 1 and 2): CL/F of TAF
CL/F is defined as the apparent clearance following oral administration of the drug.
Time frame: Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits
Population: Participants in the IPK Analysis Set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 2: Part A - Groups 1 and 2): CL/F of TAF | 174.3 L/hr | Standard Deviation 156.75 |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 2: Part A - Groups 1 and 2): CL/F of TAF | 102.1 L/hr | Standard Deviation 60.75 |
Secondary
PK Parameter (Cohort 2: Part A - Groups 1 and 2): Cmax of TAF, FTC, and TFV
Cmax is defined as the maximum concentration of drug.
Time frame: Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits
Population: Participants in the IPK Analysis Set were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 2: Part A - Groups 1 and 2): Cmax of TAF, FTC, and TFV | Cmax of TAF | 230.4 ng/mL | Standard Deviation 264.7 |
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 2: Part A - Groups 1 and 2): Cmax of TAF, FTC, and TFV | Cmax of FTC | 2074.4 ng/mL | Standard Deviation 565.91 |
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 2: Part A - Groups 1 and 2): Cmax of TAF, FTC, and TFV | Cmax of TFV | 55.8 ng/mL | Standard Deviation 19.2 |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 2: Part A - Groups 1 and 2): Cmax of TAF, FTC, and TFV | Cmax of TFV | 48.1 ng/mL | Standard Deviation 8.07 |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 2: Part A - Groups 1 and 2): Cmax of TAF, FTC, and TFV | Cmax of FTC | 2020.0 ng/mL | Standard Deviation 1151.91 |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 2: Part A - Groups 1 and 2): Cmax of TAF, FTC, and TFV | Cmax of TAF | 232.0 ng/mL | Standard Deviation 253.59 |
Secondary
PK Parameter (Cohort 2: Part A - Groups 1 and 2): Ctau of FTC and TFV
Ctau is defined as the observed drug concentration at the end of the dosing interval.
Time frame: Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits
Population: Participants in the IPK Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 2: Part A - Groups 1 and 2): Ctau of FTC and TFV | Ctau of FTC | 75.4 ng/mL | Standard Deviation 22.71 |
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 2: Part A - Groups 1 and 2): Ctau of FTC and TFV | Ctau of TFV | 34.8 ng/mL | Standard Deviation 16.39 |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 2: Part A - Groups 1 and 2): Ctau of FTC and TFV | Ctau of FTC | 75.4 ng/mL | Standard Deviation 27.63 |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 2: Part A - Groups 1 and 2): Ctau of FTC and TFV | Ctau of TFV | 30.9 ng/mL | Standard Deviation 3.53 |
Secondary
PK Parameter (Cohort 2: Part A - Groups 1 and 2): Vz/F of TAF
Vz/F is defined as the apparent volume of distribution of the drug following oral administration.
Time frame: Any time at Week 2 or Week 4 visit, or within 7 days after the completion of Week 2 or Week 4 visits
Population: Participants in the IPK Analysis Set were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| F/TAF 200/10 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 2: Part A - Groups 1 and 2): Vz/F of TAF | 160.8 liters | Standard Deviation 145.57 |
| F/TAF 200/25 mg+3rd ARV Agent (Cohort 1) | PK Parameter (Cohort 2: Part A - Groups 1 and 2): Vz/F of TAF | 63.1 liters | Standard Deviation 63.39 |