Trial Outcomes & Findings for Safety and Efficacy of Tenofovir DF in HIV-1 Infected Adolescents Failing Their Current Antiretroviral Therapy (NCT NCT00352053)

Results Overview

DAVG24 was defined as the time-weighted average between the first postbaseline value through the last value up to Week 24 minus the baseline value. DAVG24 was calculated using the trapezoidal rule with all available postbaseline data minus the baseline value. Data for participants who discontinued the randomized (double-blind) phase of the study early were included up until the point of study discontinuation (missing data not imputed).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

87 participants

Primary outcome timeframe

Baseline to 24 Weeks

Results posted on

2015-07-14

Participant Flow

There were 17 sites in Brazil and 1 site in Panama. First participant was screened on 13 June 2006. The last study visit occurred on 19 December 2013.

123 participants were screened.

Participant milestones

Participant milestones
Measure	Tenofovir DF Tenofovir disoproxil fumarate (tenofovir DF; TDF) 300 mg tablets plus a genotype-guided optimized background regimen (OBR; 3 minimum (min.)/5 maximum (max.) antiretroviral agents (ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks.	Placebo Placebo to match TDF plus a genotype-guided OBR (3 min./5 max. ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks.
Double-Blind Phase (Through Week 48) STARTED	45	42
Double-Blind Phase (Through Week 48) COMPLETED	27	29
Double-Blind Phase (Through Week 48) NOT COMPLETED	18	13
First Extension Phase (Weeks 48-144) STARTED	24	36
First Extension Phase (Weeks 48-144) COMPLETED	12	19
First Extension Phase (Weeks 48-144) NOT COMPLETED	12	17
Second Extension Phase (Weeks 144-240) STARTED	9	14
Second Extension Phase (Weeks 144-240) COMPLETED	4	9
Second Extension Phase (Weeks 144-240) NOT COMPLETED	5	5
Third Extension Phase (Weeks 240-294) STARTED	1	4
Third Extension Phase (Weeks 240-294) COMPLETED	0	2
Third Extension Phase (Weeks 240-294) NOT COMPLETED	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Tenofovir DF Tenofovir disoproxil fumarate (tenofovir DF; TDF) 300 mg tablets plus a genotype-guided optimized background regimen (OBR; 3 minimum (min.)/5 maximum (max.) antiretroviral agents (ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks.	Placebo Placebo to match TDF plus a genotype-guided OBR (3 min./5 max. ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks.
Double-Blind Phase (Through Week 48) Virologic Failure	14	10
Double-Blind Phase (Through Week 48) Physician Decision	2	2
Double-Blind Phase (Through Week 48) Adverse Event	1	0
Double-Blind Phase (Through Week 48) Withdrawal by Subject	0	1
Double-Blind Phase (Through Week 48) Intolerance to Antiretroviral Regimen	1	0
First Extension Phase (Weeks 48-144) Physician Decision	9	13
First Extension Phase (Weeks 48-144) Lack of Efficacy	1	4
First Extension Phase (Weeks 48-144) Pregnancy	1	0
First Extension Phase (Weeks 48-144) Lost to Follow-up	1	0
Second Extension Phase (Weeks 144-240) Physician Decision	4	4
Second Extension Phase (Weeks 144-240) Withdrawal by Subject	1	1
Third Extension Phase (Weeks 240-294) Lack of Efficacy	1	1
Third Extension Phase (Weeks 240-294) Withdrawal by Subject	0	1

Baseline Characteristics

Safety and Efficacy of Tenofovir DF in HIV-1 Infected Adolescents Failing Their Current Antiretroviral Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tenofovir DF n=45 Participants TDF 300 mg tablets plus a genotype-guided OBR (3 min./5 max. ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks.	Placebo n=42 Participants Placebo to match TDF plus a genotype-guided OBR (3 min./5 max. ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks.	Total n=87 Participants Total of all reporting groups
Age, Categorical <=18 years	45 Participants n=5 Participants	42 Participants n=7 Participants	87 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	14 years STANDARD_DEVIATION 1.5 • n=5 Participants	14 years STANDARD_DEVIATION 1.5 • n=7 Participants	14 years STANDARD_DEVIATION 1.5 • n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	25 Participants n=7 Participants	49 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	17 Participants n=7 Participants	38 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	45 Participants n=5 Participants	42 Participants n=7 Participants	87 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	23 Participants n=5 Participants	22 Participants n=7 Participants	45 Participants n=5 Participants
Race/Ethnicity, Customized Black or African Heritage	14 Participants n=5 Participants	11 Participants n=7 Participants	25 Participants n=5 Participants
Race/Ethnicity, Customized Mulatto	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized Mixed Race	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Indian Descendant	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Mestizo	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Black and White Race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized South American Indian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Panama	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment Brazil	43 participants n=5 Participants	40 participants n=7 Participants	83 participants n=5 Participants
Body Mass Index	18.72 kg/m^2 STANDARD_DEVIATION 2.304 • n=5 Participants	19.99 kg/m^2 STANDARD_DEVIATION 3.238 • n=7 Participants	19.33 kg/m^2 STANDARD_DEVIATION 2.849 • n=5 Participants
CD4 Cell Count	390 cells/mm^3 STANDARD_DEVIATION 244.0 • n=5 Participants	357 cells/mm^3 STANDARD_DEVIATION 200.8 • n=7 Participants	374 cells/mm^3 STANDARD_DEVIATION 223.5 • n=5 Participants
CD4 Percentage	17.8 Percentage of CD4 lymphocytes STANDARD_DEVIATION 9.70 • n=5 Participants	17.6 Percentage of CD4 lymphocytes STANDARD_DEVIATION 8.31 • n=7 Participants	17.7 Percentage of CD4 lymphocytes STANDARD_DEVIATION 9.00 • n=5 Participants
Height	155.84 cm STANDARD_DEVIATION 10.071 • n=5 Participants	156.05 cm STANDARD_DEVIATION 8.569 • n=7 Participants	155.94 cm STANDARD_DEVIATION 9.322 • n=5 Participants
Human Immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA)	4.71 log10 copies/mL STANDARD_DEVIATION 0.723 • n=5 Participants	4.56 log10 copies/mL STANDARD_DEVIATION 0.746 • n=7 Participants	4.64 log10 copies/mL STANDARD_DEVIATION 0.734 • n=5 Participants
Weight	45.84 kg STANDARD_DEVIATION 9.639 • n=5 Participants	49.09 kg STANDARD_DEVIATION 11.342 • n=7 Participants	47.41 kg STANDARD_DEVIATION 10.561 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 24 Weeks

Population: Intent-to-treat (ITT) Analysis Set: participants who were randomized and received at least 1 dose of study drug, with baseline HIV-1 RNA ≥ 1000 copies/mL and who had no major eligibility criteria violations.

DAVG24 was defined as the time-weighted average between the first postbaseline value through the last value up to Week 24 minus the baseline value. DAVG24 was calculated using the trapezoidal rule with all available postbaseline data minus the baseline value. Data for participants who discontinued the randomized (double-blind) phase of the study early were included up until the point of study discontinuation (missing data not imputed).

Outcome measures

Outcome measures
Measure	Tenofovir DF n=44 Participants TDF 300 mg tablets plus a genotype-guided OBR (3 min./5 max. ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks. The analysis time point is calculated as the number of weeks after randomization. Only data collected during the double-blind phase are included.	Placebo n=41 Participants Placebo to match TDF plus a genotype-guided OBR (3 min./5 max. ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks. The analysis time point is calculated as the number of weeks after randomization. Only data collected during the double-blind phase are included.	Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Participants who were randomized to placebo and switched to open-label TDF 300 mg tablets (plus OBR) with HIV-1 RNA \< 1000 copies/mL at the time of the switch when a new baseline was established. The analysis time point is calculated as the number of weeks after the switch.	Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL Participants who were randomized to placebo and switched to open-label TDF 300 mg tablets (plus OBR) with HIV-1 RNA ≥ 1000 copies/mL at the time of the switch when a new baseline was established. The analysis time point is calculated as the number of weeks after the switch.
Time-weighted Average Change From Baseline Through Week 24 (DAVG24) in Plasma HIV-1 RNA	-1.580 log10 copies/mL Interval -2.15 to -0.27	-1.549 log10 copies/mL Interval -2.36 to -0.34	—	—

SECONDARY outcome

Timeframe: Baseline to 48 weeks

Population: ITT Analysis Set

DAVG48 was defined as the time-weighted average between the first postbaseline value through the last value up to Week 48 minus the baseline value. DAVG48 was calculated using the trapezoidal rule with all available postbaseline data minus the baseline value. Data for participants who discontinued the double-blind phase of the study early were included up until the point of discontinuation from the study (ie, missing data were not imputed).

Outcome measures

Outcome measures
Measure	Tenofovir DF n=44 Participants TDF 300 mg tablets plus a genotype-guided OBR (3 min./5 max. ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks. The analysis time point is calculated as the number of weeks after randomization. Only data collected during the double-blind phase are included.	Placebo n=41 Participants Placebo to match TDF plus a genotype-guided OBR (3 min./5 max. ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks. The analysis time point is calculated as the number of weeks after randomization. Only data collected during the double-blind phase are included.	Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Participants who were randomized to placebo and switched to open-label TDF 300 mg tablets (plus OBR) with HIV-1 RNA \< 1000 copies/mL at the time of the switch when a new baseline was established. The analysis time point is calculated as the number of weeks after the switch.	Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL Participants who were randomized to placebo and switched to open-label TDF 300 mg tablets (plus OBR) with HIV-1 RNA ≥ 1000 copies/mL at the time of the switch when a new baseline was established. The analysis time point is calculated as the number of weeks after the switch.
Time-weighted Average Change From Baseline Through Week 48 (DAVG48) in Plasma HIV-1 RNA	-1.423 log10 copies/mL Interval -2.25 to -0.25	-1.352 log10 copies/mL Interval -2.72 to -0.53	—	—

SECONDARY outcome

Timeframe: Baseline to 24 weeks

Population: ITT Analysis Set. The Tenofovir DF and Placebo groups were analyzed using the last observation carried forward (LOCF) method (includes the participant's last available postbaseline value for missing data). The Placebo/TDF groups were analyzed using the missing = excluded method (participants with missing data were excluded from the analysis).

Outcome measures

Outcome measures
Measure	Tenofovir DF n=44 Participants TDF 300 mg tablets plus a genotype-guided OBR (3 min./5 max. ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks. The analysis time point is calculated as the number of weeks after randomization. Only data collected during the double-blind phase are included.	Placebo n=41 Participants Placebo to match TDF plus a genotype-guided OBR (3 min./5 max. ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks. The analysis time point is calculated as the number of weeks after randomization. Only data collected during the double-blind phase are included.	Placebo/TDF, HIV-1 RNA < 1000 Copies/mL n=18 Participants Participants who were randomized to placebo and switched to open-label TDF 300 mg tablets (plus OBR) with HIV-1 RNA \< 1000 copies/mL at the time of the switch when a new baseline was established. The analysis time point is calculated as the number of weeks after the switch.	Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL n=16 Participants Participants who were randomized to placebo and switched to open-label TDF 300 mg tablets (plus OBR) with HIV-1 RNA ≥ 1000 copies/mL at the time of the switch when a new baseline was established. The analysis time point is calculated as the number of weeks after the switch.
Change From Baseline to Week 24 in HIV-1 RNA	-1.23 log10 copies/mL Interval -2.3 to -0.1	-1.27 log10 copies/mL Interval -2.8 to -0.1	0.0 log10 copies/mL Interval 0.0 to 0.0	-0.1 log10 copies/mL Interval -0.6 to 0.3

SECONDARY outcome

Timeframe: Baseline to 48 weeks

Population: ITT Analysis Set. The Tenofovir DF and Placebo groups were analyzed using the LOCF method. The Placebo/TDF groups were analyzed using the missing = excluded method.

Outcome measures

Outcome measures
Measure	Tenofovir DF n=44 Participants TDF 300 mg tablets plus a genotype-guided OBR (3 min./5 max. ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks. The analysis time point is calculated as the number of weeks after randomization. Only data collected during the double-blind phase are included.	Placebo n=41 Participants Placebo to match TDF plus a genotype-guided OBR (3 min./5 max. ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks. The analysis time point is calculated as the number of weeks after randomization. Only data collected during the double-blind phase are included.	Placebo/TDF, HIV-1 RNA < 1000 Copies/mL n=18 Participants Participants who were randomized to placebo and switched to open-label TDF 300 mg tablets (plus OBR) with HIV-1 RNA \< 1000 copies/mL at the time of the switch when a new baseline was established. The analysis time point is calculated as the number of weeks after the switch.	Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL n=8 Participants Participants who were randomized to placebo and switched to open-label TDF 300 mg tablets (plus OBR) with HIV-1 RNA ≥ 1000 copies/mL at the time of the switch when a new baseline was established. The analysis time point is calculated as the number of weeks after the switch.
Change From Baseline to Week 48 in HIV-1 RNA	-0.97 log10 copies/mL Interval -2.3 to 0.0	-1.53 log10 copies/mL Interval -3.0 to 0.0	0.0 log10 copies/mL Interval 0.0 to 0.6	0.2 log10 copies/mL Interval -0.1 to 0.5

SECONDARY outcome

Timeframe: Baseline to 96 weeks

Population: ITT Analysis Set, missing = excluded method

Outcome measures

Outcome measures
Measure	Tenofovir DF n=19 Participants TDF 300 mg tablets plus a genotype-guided OBR (3 min./5 max. ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks. The analysis time point is calculated as the number of weeks after randomization. Only data collected during the double-blind phase are included.	Placebo n=17 Participants Placebo to match TDF plus a genotype-guided OBR (3 min./5 max. ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks. The analysis time point is calculated as the number of weeks after randomization. Only data collected during the double-blind phase are included.	Placebo/TDF, HIV-1 RNA < 1000 Copies/mL n=3 Participants Participants who were randomized to placebo and switched to open-label TDF 300 mg tablets (plus OBR) with HIV-1 RNA \< 1000 copies/mL at the time of the switch when a new baseline was established. The analysis time point is calculated as the number of weeks after the switch.	Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL Participants who were randomized to placebo and switched to open-label TDF 300 mg tablets (plus OBR) with HIV-1 RNA ≥ 1000 copies/mL at the time of the switch when a new baseline was established. The analysis time point is calculated as the number of weeks after the switch.
Change From Baseline to Week 96 in HIV-1 RNA	-2.1 log10 copies/mL Interval -2.5 to -0.6	0.0 log10 copies/mL Interval 0.0 to 0.9	0.1 log10 copies/mL Interval -1.4 to 0.8	—

SECONDARY outcome

Timeframe: Baseline to 144 weeks

Population: ITT Analysis Set, missing = excluded method

Outcome measures

Outcome measures
Measure	Tenofovir DF n=10 Participants TDF 300 mg tablets plus a genotype-guided OBR (3 min./5 max. ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks. The analysis time point is calculated as the number of weeks after randomization. Only data collected during the double-blind phase are included.	Placebo n=11 Participants Placebo to match TDF plus a genotype-guided OBR (3 min./5 max. ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks. The analysis time point is calculated as the number of weeks after randomization. Only data collected during the double-blind phase are included.	Placebo/TDF, HIV-1 RNA < 1000 Copies/mL n=2 Participants Participants who were randomized to placebo and switched to open-label TDF 300 mg tablets (plus OBR) with HIV-1 RNA \< 1000 copies/mL at the time of the switch when a new baseline was established. The analysis time point is calculated as the number of weeks after the switch.	Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL Participants who were randomized to placebo and switched to open-label TDF 300 mg tablets (plus OBR) with HIV-1 RNA ≥ 1000 copies/mL at the time of the switch when a new baseline was established. The analysis time point is calculated as the number of weeks after the switch.
Change From Baseline to Week 144 in HIV-1 RNA	-2.5 log10 copies/mL Interval -2.7 to -2.2	0.2 log10 copies/mL Interval 0.0 to 1.6	0.7 log10 copies/mL Interval 0.6 to 0.8	—

SECONDARY outcome

Timeframe: Baseline to 192 weeks

Population: ITT Analysis Set, missing = excluded method

Outcome measures

Outcome measures
Measure	Tenofovir DF n=7 Participants TDF 300 mg tablets plus a genotype-guided OBR (3 min./5 max. ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks. The analysis time point is calculated as the number of weeks after randomization. Only data collected during the double-blind phase are included.	Placebo n=5 Participants Placebo to match TDF plus a genotype-guided OBR (3 min./5 max. ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks. The analysis time point is calculated as the number of weeks after randomization. Only data collected during the double-blind phase are included.	Placebo/TDF, HIV-1 RNA < 1000 Copies/mL n=2 Participants Participants who were randomized to placebo and switched to open-label TDF 300 mg tablets (plus OBR) with HIV-1 RNA \< 1000 copies/mL at the time of the switch when a new baseline was established. The analysis time point is calculated as the number of weeks after the switch.	Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL Participants who were randomized to placebo and switched to open-label TDF 300 mg tablets (plus OBR) with HIV-1 RNA ≥ 1000 copies/mL at the time of the switch when a new baseline was established. The analysis time point is calculated as the number of weeks after the switch.
Change From Baseline to Week 192 in HIV-1 RNA	-2.0 log10 copies/mL Interval -2.5 to -0.7	0.0 log10 copies/mL Interval 0.0 to 0.2	-0.1 log10 copies/mL Interval -1.4 to 1.3	—

SECONDARY outcome

Timeframe: Baseline to 240 weeks

Population: ITT Analysis Set, missing = excluded method

Outcome measures

Outcome measures
Measure	Tenofovir DF n=4 Participants TDF 300 mg tablets plus a genotype-guided OBR (3 min./5 max. ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks. The analysis time point is calculated as the number of weeks after randomization. Only data collected during the double-blind phase are included.	Placebo n=2 Participants Placebo to match TDF plus a genotype-guided OBR (3 min./5 max. ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks. The analysis time point is calculated as the number of weeks after randomization. Only data collected during the double-blind phase are included.	Placebo/TDF, HIV-1 RNA < 1000 Copies/mL n=1 Participants Participants who were randomized to placebo and switched to open-label TDF 300 mg tablets (plus OBR) with HIV-1 RNA \< 1000 copies/mL at the time of the switch when a new baseline was established. The analysis time point is calculated as the number of weeks after the switch.	Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL Participants who were randomized to placebo and switched to open-label TDF 300 mg tablets (plus OBR) with HIV-1 RNA ≥ 1000 copies/mL at the time of the switch when a new baseline was established. The analysis time point is calculated as the number of weeks after the switch.
Change From Baseline to Week 240 in HIV-1 RNA	-2.5 log10 copies/mL Interval -2.6 to -2.2	-0.4 log10 copies/mL Interval -0.8 to 0.0	-1.4 log10 copies/mL Interval -1.4 to -1.4	—

SECONDARY outcome

Timeframe: Baseline to 288 weeks

Population: ITT Analysis Set, missing = excluded method

Outcome measures

Outcome measures
Measure	Tenofovir DF n=1 Participants TDF 300 mg tablets plus a genotype-guided OBR (3 min./5 max. ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks. The analysis time point is calculated as the number of weeks after randomization. Only data collected during the double-blind phase are included.	Placebo n=1 Participants Placebo to match TDF plus a genotype-guided OBR (3 min./5 max. ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks. The analysis time point is calculated as the number of weeks after randomization. Only data collected during the double-blind phase are included.	Placebo/TDF, HIV-1 RNA < 1000 Copies/mL n=1 Participants Participants who were randomized to placebo and switched to open-label TDF 300 mg tablets (plus OBR) with HIV-1 RNA \< 1000 copies/mL at the time of the switch when a new baseline was established. The analysis time point is calculated as the number of weeks after the switch.	Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL Participants who were randomized to placebo and switched to open-label TDF 300 mg tablets (plus OBR) with HIV-1 RNA ≥ 1000 copies/mL at the time of the switch when a new baseline was established. The analysis time point is calculated as the number of weeks after the switch.
Change From Baseline to Week 288 in HIV-1 RNA	-1.1 log10 copies/mL Interval -1.1 to -1.1	-0.8 log10 copies/mL Interval -0.8 to -0.8	0.6 log10 copies/mL Interval 0.6 to 0.6	—

SECONDARY outcome

Timeframe: Baseline to 336 weeks

Timeframe: Baseline to 336 weeks

Timeframe: Week 336

Timeframe: Week 336

Population: ITT Analysis Set, missing = excluded method

No analysis was performed because the last study participant discontinued after Week 294 and the study was closed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 48 weeks

Population: ITT Analysis Set. 1 participant without time to respond \[6 days of treatment\]) was excluded. Nonresponders were counted as failures at time 0. Rebounders were counted as failures on study day of the first of 2 assessments meeting criteria. Otherwise, they were censored at last double-blind HIV measurement.

Virologic failure was defined as either nonresponse or viral rebound. * Nonresponse (failure to achieve response). Response was defined as either * A ≥ 0.5 log10 copies/mL decrease in HIV-1 RNA from baseline at 2 consecutive visits, or * HIV-1 RNA \< 400 copies/mL at 2 consecutive visits. * Viral rebound was defined as either * Participants who achieved a ≥ 0.5 log10 copies/mL decrease from baseline in plasma HIV-1 RNA at 2 consecutive visits, who then subsequently achieved plasma HIV-1 RNA values ≥ 1.0 log10 copies/mL above their on-study nadir (lowest value) and/or plasma HIV-1 RNA values ≥ the baseline value at 2 consecutive visits, or * Participants who achieved plasma HIV-1 RNA levels of \< 400 copies/mL at 2 consecutive visits, and then subsequently had plasma HIV-1 RNA levels \> 1000 copies/mL at 2 consecutive visits. The virologic failure rate was estimated from Kaplan-Meier product limit method by including all HIV-1 RNA data collected during the double-blind phase.

Outcome measures

Outcome measures
Measure	Tenofovir DF n=43 Participants TDF 300 mg tablets plus a genotype-guided OBR (3 min./5 max. ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks. The analysis time point is calculated as the number of weeks after randomization. Only data collected during the double-blind phase are included.	Placebo n=41 Participants Placebo to match TDF plus a genotype-guided OBR (3 min./5 max. ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks. The analysis time point is calculated as the number of weeks after randomization. Only data collected during the double-blind phase are included.	Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Participants who were randomized to placebo and switched to open-label TDF 300 mg tablets (plus OBR) with HIV-1 RNA \< 1000 copies/mL at the time of the switch when a new baseline was established. The analysis time point is calculated as the number of weeks after the switch.	Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL Participants who were randomized to placebo and switched to open-label TDF 300 mg tablets (plus OBR) with HIV-1 RNA ≥ 1000 copies/mL at the time of the switch when a new baseline was established. The analysis time point is calculated as the number of weeks after the switch.
Percentage of Participants With Virologic Failure Through Week 48	51 Kaplan-Meier percentage	39 Kaplan-Meier percentage	—	—

Adverse Events

Tenofovir DF

Serious events: 10 serious events

Other events: 44 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 35 other events

Deaths: 0 deaths

All TDF

Serious events: 20 serious events

Other events: 76 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Trial Disclosures

Gilead Sciences

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
Publication restrictions are in place

Restriction type: OTHER

Measure	Tenofovir DF n=45 participants at risk Adverse events occurring in the double-blind phase are presented for this reporting group. TDF 300 mg tablets plus a genotype-guided OBR (3 min./5 max. ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks.	Placebo n=42 participants at risk Adverse events occurring in the double-blind phase are presented for this reporting group. Placebo to match TDF plus a genotype-guided OBR (3 min./5 max. ARVs) from baseline to Week 48 (double-blind phase), followed by open-label TDF 300 mg plus OBR for up to an additional 288 weeks.	All TDF n=81 participants at risk Adverse events reported for the All TDF group include those reported during the double-blind phase and/or extension phase for subjects who were randomized to TDF group plus adverse events reported during the extension phase only for subjects who switched from placebo to open-label TDF. Tenofovir DF 300-mg tablets in participants initially randomized to the Tenofovir DF group, and in those initially randomized to the Placebo group who later switched to open-label TDF 300 mg.
Blood and lymphatic system disorders Neutropenia	0.00% 0/45 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	0.00% 0/42 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	1.2% 1/81 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.
Infections and infestations Pneumonia	6.7% 3/45 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	2.4% 1/42 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	6.2% 5/81 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.
Infections and infestations Sinusitis	4.4% 2/45 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	0.00% 0/42 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	2.5% 2/81 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.
Infections and infestations Herpes Zoster	0.00% 0/45 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	0.00% 0/42 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	3.7% 3/81 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.
Infections and infestations Cryptococcosis	2.2% 1/45 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	0.00% 0/42 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	1.2% 1/81 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.
Infections and infestations Gastroenteritis	2.2% 1/45 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	0.00% 0/42 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	1.2% 1/81 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.
Infections and infestations Pneumocystis Jiroveci Pneumonia	4.4% 2/45 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	0.00% 0/42 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	2.5% 2/81 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.
Infections and infestations Respiratory Tract Infection	2.2% 1/45 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	0.00% 0/42 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	1.2% 1/81 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.
Infections and infestations Urinary Tract Infection	2.2% 1/45 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	0.00% 0/42 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	1.2% 1/81 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.
Infections and infestations Abscess	0.00% 0/45 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	0.00% 0/42 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	1.2% 1/81 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.
Infections and infestations Abscess Limb	0.00% 0/45 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	0.00% 0/42 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	1.2% 1/81 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.
Infections and infestations Cellulitis	0.00% 0/45 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	2.4% 1/42 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	0.00% 0/81 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.
Infections and infestations Cerebral Toxoplasmosis	0.00% 0/45 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	2.4% 1/42 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	0.00% 0/81 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.
Infections and infestations Mastoiditis	0.00% 0/45 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	2.4% 1/42 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	0.00% 0/81 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.
Infections and infestations Neurocryptococcosis	0.00% 0/45 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	0.00% 0/42 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	1.2% 1/81 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.
Infections and infestations Pyelonephritis	0.00% 0/45 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	0.00% 0/42 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	1.2% 1/81 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.
Injury, poisoning and procedural complications Overdose	0.00% 0/45 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	0.00% 0/42 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	1.2% 1/81 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Anogenital Warts	0.00% 0/45 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	0.00% 0/42 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	1.2% 1/81 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.
Nervous system disorders Convulsion	2.2% 1/45 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	0.00% 0/42 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	1.2% 1/81 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.
Psychiatric disorders Psychotic Disorder	0.00% 0/45 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	0.00% 0/42 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	1.2% 1/81 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.
Psychiatric disorders Suicide Attempt	0.00% 0/45 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	0.00% 0/42 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	1.2% 1/81 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.
Renal and urinary disorders Proteinuria	2.2% 1/45 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	0.00% 0/42 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.	1.2% 1/81 • Up to Week 294 plus 30 days. Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column.