HIV Infections
Conditions
Keywords
Phase 3, Randomized, Double-Blind, Control, Treatment-Experienced, OBR, Optimized background regimen, Highly Active Antiretroviral Therapy, HAART, HIV, HIV-1, AIDS Virus, Human Immunodeficiency Virus, Acquired Immune Deficiency Syndrome Virus, Virus, Human Immunodeficiency, Pediatrics
Brief summary
The purpose of this study is to assess the safety and efficacy of tenofovir disoproxil fumarate (tenofovir DF; TDF) plus a genotype-guided optimized background regimen (OBR) compared to placebo plus OBR in the treatment of human immunodeficiency virus type 1 (HIV-1) infected antiretroviral treatment-experienced adolescents with plasma HIV-1 ribonucleic acid (RNA) levels greater than or equal to 1000 copies/mL.
Detailed description
This is a 48-week, randomized, double-blind, placebo-controlled, multicenter study of the safety and efficacy of tenofovir DF as part of an optimized antiretroviral regimen in HIV-1 infected adolescents (12 years to \< 18 years of age) who are failing their current antiretroviral regimen and have HIV-1 RNA levels ≥ 1000 copies/mL at screening. Data from three consecutive 96-week study extensions have been used to evaluate the long-term efficacy, safety, and tolerability of open-label tenofovir DF as part of an antiviral regimen, providing data for up to 336 weeks of total drug exposure. Pretreatment: HIV-1 genotyping will be performed as part of the screening assessments to assist in the construction of an OBR, defined as at least 3, but no more than 5 antiretroviral agents, not including tenofovir DF or placebo. Randomized Phase: Participants will be randomized in a 1:1 ratio to receive either tenofovir DF + OBR, or placebo + OBR. The majority of efficacy and safety assessments will be performed at each clinic visit (Weeks 4, 8, 16, 24, 32, 40, and 48). At Week 24, participants who are adherent to study drug (in the opinion of the investigator), but do not demonstrate a ≥ 0.5 log10 copies/mL decrease from baseline in HIV-1 RNA, will be considered to be nonresponders and will be unblinded. Nonresponders randomized to the placebo group will be given the option to continue on study and receive open-label tenofovir DF with an appropriate background regimen determined by the investigator. Nonresponders randomized to the tenofovir DF treatment group will be discontinued from the study. Extension Phases: After completing 48 weeks of double-blind treatment with tenofovir DF or placebo, participants who have not reached 18 years of age, and who, in the opinion of the investigator, would derive clinical benefit from the use of open-label tenofovir DF, will be given the option to continue (or initiate) treatment with open-label tenofovir DF in the first of three 96 week study extension periods. Nonresponders who receive open-label tenofovir DF after Week 24 will also be considered eligible for the first study extension if they met the above criteria at Week 48. After completing the first 96 week study extension, participants who have not reached 18 years of age, and who have shown ongoing clinical benefit from tenofovir DF, will be given the option to continue receiving open-label tenofovir DF for an additional 96 weeks or until tenofovir DF became commercially available in the country where the participants are enrolled, whichever occurs first. After completing the second 96 week study extension, participants who have not reached 18 years of age, and who have shown ongoing clinical benefit from tenofovir DF, will be given the option to continue receiving open-label tenofovir DF for an additional 96 weeks or until tenofovir DF became commercially available in the country where the participants are enrolled, whichever occurs first. Presentation of data: After the randomized phase of the study, participants randomized to placebo during the randomized phase of the study and then switch to open-label tenofovir DF will have their baseline reset (defined as open-label baseline), and only outcome data collected after (on/after for adverse events (AEs)/concomitant medications) participants receive their first dose of open-label tenofovir DF will be included.
Interventions
DRUGTenofovir DF
Tenofovir DF 300-mg tablet, administered orally, daily + OBR
DRUGPlacebo
Tenofovir DF Placebo administered orally, daily + OBR
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
Major Inclusion Criteria: * Weight ≥ 35 kg * Documented laboratory diagnosis of HIV infection * Plasma HIV-1 RNA ≥ 1000 copies/mL * Prior antiretroviral treatment experience with at least 2 antiretroviral drug classes * Naive to tenofovir DF * Absence of K65R mutation on genotypic testing
Exclusion criteria
* Patients requiring didanosine in background regimen * Prior history of significant renal disease * Prior history of significant bone disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time-weighted Average Change From Baseline Through Week 24 (DAVG24) in Plasma HIV-1 RNA | Baseline to 24 Weeks | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 192 | Week 192 | — |
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 240 | Week 240 | — |
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 288 | Week 288 | — |
| Time-weighted Average Change From Baseline Through Week 48 (DAVG48) in Plasma HIV-1 RNA | Baseline to 48 weeks | 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). |
| Change From Baseline to Week 24 in HIV-1 RNA | Baseline to 24 weeks | — |
| Change From Baseline to Week 48 in HIV-1 RNA | Baseline to 48 weeks | — |
| Change From Baseline to Week 96 in HIV-1 RNA | Baseline to 96 weeks | — |
| Change From Baseline to Week 144 in HIV-1 RNA | Baseline to 144 weeks | — |
| Change From Baseline to Week 192 in HIV-1 RNA | Baseline to 192 weeks | — |
| Change From Baseline to Week 240 in HIV-1 RNA | Baseline to 240 weeks | — |
| Change From Baseline to Week 288 in HIV-1 RNA | Baseline to 288 weeks | — |
| Change From Baseline to Week 336 in HIV-1 RNA | Baseline to 336 weeks | No analysis was performed because the last study participant discontinued after Week 294 and the study was closed. |
| Change From Baseline to Week 24 in Cluster Determinant 4 (CD4) Count | Baseline to 24 weeks | — |
| Change From Baseline to Week 48 in CD4 Count | Baseline to 48 weeks | — |
| Change From Baseline to Week 96 in CD4 Count | Baseline to 96 weeks | — |
| Change From Baseline to Week 144 in CD4 Count | Baseline to 144 weeks | — |
| Change From Baseline to Week 192 in CD4 Count | Baseline to 192 weeks | — |
| Change From Baseline to Week 240 in CD4 Count | Baseline to 240 weeks | — |
| Change From Baseline to Week 288 in CD4 Count | Baseline to 288 weeks | — |
| Change From Baseline to Week 336 in CD4 Count | Baseline to 336 weeks | No analysis was performed because the last study participant discontinued after Week 294 and the study was closed. |
| Change From Baseline to Week 24 in CD4 Percentage | Baseline to 24 weeks | CD4 percentage is the percentage of total lymphocytes that are CD4 cells. |
| Change From Baseline to Week 48 in CD4 Percentage | Baseline to 48 weeks | CD4 percentage is the percentage of total lymphocytes that are CD4 cells. |
| Change From Baseline to Week 96 in CD4 Percentage | Baseline to 96 weeks | CD4 percentage is the percentage of total lymphocytes that are CD4 cells. |
| Change From Baseline to Week 144 in CD4 Percentage | Baseline to 144 weeks | CD4 percentage is the percentage of total lymphocytes that are CD4 cells. |
| Change From Baseline to Week 192 in CD4 Percentage | Baseline to 192 weeks | CD4 percentage is the percentage of total lymphocytes that are CD4 cells. |
| Change From Baseline to Week 240 in CD4 Percentage | Baseline to 240 weeks | CD4 percentage is the percentage of total lymphocytes that are CD4 cells. |
| Change From Baseline to Week 288 in CD4 Percentage | Baseline to 288 weeks | CD4 percentage is the percentage of total lymphocytes that are CD4 cells. |
| Change From Baseline to Week 336 in CD4 Percentage | Baseline to 336 weeks | No analysis was performed because the last study participant discontinued after Week 294 and the study was closed. |
| Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 24 | Baseline to 24 weeks | — |
| Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 48 | Baseline to 48 weeks | — |
| Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 96 | Baseline to 96 weeks | — |
| Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 144 | Baseline to 144 weeks | — |
| Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 192 | Baseline to 192 weeks | — |
| Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 240 | Baseline to 240 weeks | — |
| Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0log 10 Copies/mL From Baseline to Week 288 | Baseline to 288 weeks | — |
| Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 336 | Baseline to 336 weeks | No analysis was performed because the last study participant discontinued after Week 294 and the study was closed. |
| Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 24 | Week 24 | — |
| Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 48 | Week 48 | — |
| Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 96 | Week 96 | — |
| Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 144 | Week 144 | — |
| Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 192 | Week 192 | — |
| Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 240 | Week 240 | — |
| Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 288 | Week 288 | — |
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 144 | Week 144 | — |
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 | Week 24 | — |
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 | Week 48 | — |
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 | Week 96 | — |
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 336 | Week 336 | No analysis was performed because the last study participant discontinued after Week 294 and the study was closed. |
| Percentage of Participants With Virologic Failure Through Week 48 | Up to 48 weeks | 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. |
| Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 336 | Week 336 | No analysis was performed because the last study participant discontinued after Week 294 and the study was closed. |
Countries
Brazil, Panama
Participant flow
Recruitment details
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.
Pre-assignment details
123 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Tenofovir DF 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. | 45 |
| 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. | 42 |
| Total | 87 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-Blind Phase (Through Week 48) | Adverse Event | 1 | 0 |
| Double-Blind Phase (Through Week 48) | Intolerance to Antiretroviral Regimen | 1 | 0 |
| Double-Blind Phase (Through Week 48) | Physician Decision | 2 | 2 |
| Double-Blind Phase (Through Week 48) | Virologic Failure | 14 | 10 |
| Double-Blind Phase (Through Week 48) | Withdrawal by Subject | 0 | 1 |
| First Extension Phase (Weeks 48-144) | Lack of Efficacy | 1 | 4 |
| First Extension Phase (Weeks 48-144) | Lost to Follow-up | 1 | 0 |
| First Extension Phase (Weeks 48-144) | Physician Decision | 9 | 13 |
| First Extension Phase (Weeks 48-144) | Pregnancy | 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
| Characteristic | Total | Placebo | Tenofovir DF |
|---|---|---|---|
| Age, Categorical <=18 years | 87 Participants | 42 Participants | 45 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 14 years STANDARD_DEVIATION 1.5 | 14 years STANDARD_DEVIATION 1.5 | 14 years STANDARD_DEVIATION 1.5 |
| Body Mass Index | 19.33 kg/m^2 STANDARD_DEVIATION 2.849 | 19.99 kg/m^2 STANDARD_DEVIATION 3.238 | 18.72 kg/m^2 STANDARD_DEVIATION 2.304 |
| CD4 Cell Count | 374 cells/mm^3 STANDARD_DEVIATION 223.5 | 357 cells/mm^3 STANDARD_DEVIATION 200.8 | 390 cells/mm^3 STANDARD_DEVIATION 244 |
| CD4 Percentage | 17.7 Percentage of CD4 lymphocytes STANDARD_DEVIATION 9 | 17.6 Percentage of CD4 lymphocytes STANDARD_DEVIATION 8.31 | 17.8 Percentage of CD4 lymphocytes STANDARD_DEVIATION 9.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 87 Participants | 42 Participants | 45 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 155.94 cm STANDARD_DEVIATION 9.322 | 156.05 cm STANDARD_DEVIATION 8.569 | 155.84 cm STANDARD_DEVIATION 10.071 |
| Human Immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) | 4.64 log10 copies/mL STANDARD_DEVIATION 0.734 | 4.56 log10 copies/mL STANDARD_DEVIATION 0.746 | 4.71 log10 copies/mL STANDARD_DEVIATION 0.723 |
| Race/Ethnicity, Customized Black and White Race | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African Heritage | 25 Participants | 11 Participants | 14 Participants |
| Race/Ethnicity, Customized Indian Descendant | 2 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Mestizo | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Mixed Race | 3 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Mulatto | 8 Participants | 4 Participants | 4 Participants |
| Race/Ethnicity, Customized South American Indian | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 45 Participants | 22 Participants | 23 Participants |
| Region of Enrollment Brazil | 83 participants | 40 participants | 43 participants |
| Region of Enrollment Panama | 4 participants | 2 participants | 2 participants |
| Sex: Female, Male Female | 49 Participants | 25 Participants | 24 Participants |
| Sex: Female, Male Male | 38 Participants | 17 Participants | 21 Participants |
| Weight | 47.41 kg STANDARD_DEVIATION 10.561 | 49.09 kg STANDARD_DEVIATION 11.342 | 45.84 kg STANDARD_DEVIATION 9.639 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 44 / 45 | 35 / 42 | 76 / 81 |
| serious Total, serious adverse events | 10 / 45 | 3 / 42 | 20 / 81 |
Outcome results
Primary
Time-weighted Average Change From Baseline Through Week 24 (DAVG24) in Plasma HIV-1 RNA
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).
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir DF | Time-weighted Average Change From Baseline Through Week 24 (DAVG24) in Plasma HIV-1 RNA | -1.580 log10 copies/mL |
| Placebo | Time-weighted Average Change From Baseline Through Week 24 (DAVG24) in Plasma HIV-1 RNA | -1.549 log10 copies/mL |
Comparison: Null hypothesis: Time-weighted average changes from baseline through Week 24 in plasma HIV-1 RNA for the tenofovir DF and placebo groups are equal. Alternative hypothesis: Time-weighted average changes from baseline through Week 24 in plasma HIV-1 RNA for the tenofovir DF and placebo groups are different (two-sided).p-value: 0.55Van Elteren test
Secondary
Change From Baseline to Week 144 in CD4 Count
Time frame: Baseline to 144 weeks
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir DF | Change From Baseline to Week 144 in CD4 Count | 188 cells/mm^3 |
| Placebo | Change From Baseline to Week 144 in CD4 Count | -88 cells/mm^3 |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Change From Baseline to Week 144 in CD4 Count | 33 cells/mm^3 |
Secondary
Change From Baseline to Week 144 in CD4 Percentage
CD4 percentage is the percentage of total lymphocytes that are CD4 cells.
Time frame: Baseline to 144 weeks
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir DF | Change From Baseline to Week 144 in CD4 Percentage | 6.5 Percentage of CD4 lymphocytes |
| Placebo | Change From Baseline to Week 144 in CD4 Percentage | 0.0 Percentage of CD4 lymphocytes |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Change From Baseline to Week 144 in CD4 Percentage | 5.5 Percentage of CD4 lymphocytes |
Secondary
Change From Baseline to Week 144 in HIV-1 RNA
Time frame: Baseline to 144 weeks
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir DF | Change From Baseline to Week 144 in HIV-1 RNA | -2.5 log10 copies/mL |
| Placebo | Change From Baseline to Week 144 in HIV-1 RNA | 0.2 log10 copies/mL |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Change From Baseline to Week 144 in HIV-1 RNA | 0.7 log10 copies/mL |
Secondary
Change From Baseline to Week 192 in CD4 Count
Time frame: Baseline to 192 weeks
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir DF | Change From Baseline to Week 192 in CD4 Count | 166 cells/mm^3 |
| Placebo | Change From Baseline to Week 192 in CD4 Count | -70 cells/mm^3 |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Change From Baseline to Week 192 in CD4 Count | -23 cells/mm^3 |
Secondary
Change From Baseline to Week 192 in CD4 Percentage
CD4 percentage is the percentage of total lymphocytes that are CD4 cells.
Time frame: Baseline to 192 weeks
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir DF | Change From Baseline to Week 192 in CD4 Percentage | 5.0 Percentage of CD4 lymphocytes |
| Placebo | Change From Baseline to Week 192 in CD4 Percentage | 1.9 Percentage of CD4 lymphocytes |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Change From Baseline to Week 192 in CD4 Percentage | 4.8 Percentage of CD4 lymphocytes |
Secondary
Change From Baseline to Week 192 in HIV-1 RNA
Time frame: Baseline to 192 weeks
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir DF | Change From Baseline to Week 192 in HIV-1 RNA | -2.0 log10 copies/mL |
| Placebo | Change From Baseline to Week 192 in HIV-1 RNA | 0.0 log10 copies/mL |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Change From Baseline to Week 192 in HIV-1 RNA | -0.1 log10 copies/mL |
Secondary
Change From Baseline to Week 240 in CD4 Count
Time frame: Baseline to 240 weeks
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir DF | Change From Baseline to Week 240 in CD4 Count | 221 cells/mm^3 |
| Placebo | Change From Baseline to Week 240 in CD4 Count | 571 cells/mm^3 |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Change From Baseline to Week 240 in CD4 Count | 258 cells/mm^3 |
Secondary
Change From Baseline to Week 240 in CD4 Percentage
CD4 percentage is the percentage of total lymphocytes that are CD4 cells.
Time frame: Baseline to 240 weeks
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir DF | Change From Baseline to Week 240 in CD4 Percentage | 10.0 Percentage of CD4 lymphocytes |
| Placebo | Change From Baseline to Week 240 in CD4 Percentage | 8.9 Percentage of CD4 lymphocytes |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Change From Baseline to Week 240 in CD4 Percentage | 18.9 Percentage of CD4 lymphocytes |
Secondary
Change From Baseline to Week 240 in HIV-1 RNA
Time frame: Baseline to 240 weeks
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir DF | Change From Baseline to Week 240 in HIV-1 RNA | -2.5 log10 copies/mL |
| Placebo | Change From Baseline to Week 240 in HIV-1 RNA | -0.4 log10 copies/mL |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Change From Baseline to Week 240 in HIV-1 RNA | -1.4 log10 copies/mL |
Secondary
Change From Baseline to Week 24 in CD4 Percentage
CD4 percentage is the percentage of total lymphocytes that are CD4 cells.
Time frame: Baseline to 24 weeks
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir DF | Change From Baseline to Week 24 in CD4 Percentage | 3.0 Percentage of CD4 lymphocytes |
| Placebo | Change From Baseline to Week 24 in CD4 Percentage | 2.0 Percentage of CD4 lymphocytes |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Change From Baseline to Week 24 in CD4 Percentage | 0.0 Percentage of CD4 lymphocytes |
| Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL | Change From Baseline to Week 24 in CD4 Percentage | -1.0 Percentage of CD4 lymphocytes |
Comparison: Null hypothesis: Changes from baseline through Week 24 in plasma CD4% for the tenofovir DF and placebo groups are equal. Alternative hypothesis: Changes from baseline through Week 24 in CD4% for the tenofovir DF and placebo groups are different (two-sided).p-value: 0.26Van Elteren test
Secondary
Change From Baseline to Week 24 in Cluster Determinant 4 (CD4) Count
Time frame: Baseline to 24 weeks
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir DF | Change From Baseline to Week 24 in Cluster Determinant 4 (CD4) Count | 69 cells/mm3 |
| Placebo | Change From Baseline to Week 24 in Cluster Determinant 4 (CD4) Count | 49 cells/mm3 |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Change From Baseline to Week 24 in Cluster Determinant 4 (CD4) Count | -43 cells/mm3 |
| Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL | Change From Baseline to Week 24 in Cluster Determinant 4 (CD4) Count | -12 cells/mm3 |
Comparison: Null hypothesis: Changes from baseline through Week 24 in plasma CD4 count for the tenofovir DF and placebo groups are equal. Alternative hypothesis: Changes from baseline through Week 24 in CD4 count for the tenofovir DF and placebo groups are different (two-sided).p-value: 0.71Van Elteren test
Secondary
Change From Baseline to Week 24 in HIV-1 RNA
Time frame: 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).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir DF | Change From Baseline to Week 24 in HIV-1 RNA | -1.23 log10 copies/mL |
| Placebo | Change From Baseline to Week 24 in HIV-1 RNA | -1.27 log10 copies/mL |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Change From Baseline to Week 24 in HIV-1 RNA | 0.0 log10 copies/mL |
| Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL | Change From Baseline to Week 24 in HIV-1 RNA | -0.1 log10 copies/mL |
Comparison: Null hypothesis: Changes from baseline through Week 24 in plasma HIV-1 RNA for the tenofovir DF and placebo groups are equal. Alternative hypothesis: Changes from baseline through Week 24 in plasma HIV-1 RNA for the tenofovir DF and placebo groups are different (two-sided).p-value: 0.58Van Elteren test
Secondary
Change From Baseline to Week 288 in CD4 Count
Time frame: Baseline to 288 weeks
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir DF | Change From Baseline to Week 288 in CD4 Count | 310 cells/mm^3 |
| Placebo | Change From Baseline to Week 288 in CD4 Count | 100 cells/mm^3 |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Change From Baseline to Week 288 in CD4 Count | 309 cells/mm^3 |
Secondary
Change From Baseline to Week 288 in CD4 Percentage
CD4 percentage is the percentage of total lymphocytes that are CD4 cells.
Time frame: Baseline to 288 weeks
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir DF | Change From Baseline to Week 288 in CD4 Percentage | 7.4 Percentage of CD4 lymphocytes |
| Placebo | Change From Baseline to Week 288 in CD4 Percentage | 4.0 Percentage of CD4 lymphocytes |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Change From Baseline to Week 288 in CD4 Percentage | 11.9 Percentage of CD4 lymphocytes |
Secondary
Change From Baseline to Week 288 in HIV-1 RNA
Time frame: Baseline to 288 weeks
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir DF | Change From Baseline to Week 288 in HIV-1 RNA | -1.1 log10 copies/mL |
| Placebo | Change From Baseline to Week 288 in HIV-1 RNA | -0.8 log10 copies/mL |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Change From Baseline to Week 288 in HIV-1 RNA | 0.6 log10 copies/mL |
Secondary
Change From Baseline to Week 336 in CD4 Count
No analysis was performed because the last study participant discontinued after Week 294 and the study was closed.
Time frame: Baseline to 336 weeks
Population: ITT Analysis Set, missing = excluded method
Secondary
Change From Baseline to Week 336 in CD4 Percentage
No analysis was performed because the last study participant discontinued after Week 294 and the study was closed.
Time frame: Baseline to 336 weeks
Population: ITT Analysis Set, missing = excluded method
Secondary
Change From Baseline to Week 336 in HIV-1 RNA
No analysis was performed because the last study participant discontinued after Week 294 and the study was closed.
Time frame: Baseline to 336 weeks
Population: ITT Analysis Set, missing = excluded method
Secondary
Change From Baseline to Week 48 in CD4 Count
Time frame: Baseline to 48 weeks
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir DF | Change From Baseline to Week 48 in CD4 Count | 152 cells/mm3 |
| Placebo | Change From Baseline to Week 48 in CD4 Count | 148 cells/mm3 |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Change From Baseline to Week 48 in CD4 Count | 15 cells/mm3 |
| Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL | Change From Baseline to Week 48 in CD4 Count | -47 cells/mm3 |
Comparison: Null hypothesis: Changes from baseline through Week 48 in plasma CD4 count for the tenofovir DF and placebo groups are equal. Alternative hypothesis: Changes from baseline through Week 48 in CD4 count for the tenofovir DF and placebo groups are different (two-sided).p-value: 0.47Van Elteren test
Secondary
Change From Baseline to Week 48 in CD4 Percentage
CD4 percentage is the percentage of total lymphocytes that are CD4 cells.
Time frame: Baseline to 48 weeks
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir DF | Change From Baseline to Week 48 in CD4 Percentage | 6.0 Percentage of CD4 lymphocytes |
| Placebo | Change From Baseline to Week 48 in CD4 Percentage | 5.0 Percentage of CD4 lymphocytes |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Change From Baseline to Week 48 in CD4 Percentage | 2.0 Percentage of CD4 lymphocytes |
| Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL | Change From Baseline to Week 48 in CD4 Percentage | -1.0 Percentage of CD4 lymphocytes |
Comparison: Null hypothesis: Changes from baseline through Week 48 in plasma CD4% for the tenofovir DF and placebo groups are equal. Alternative hypothesis: Changes from baseline through Week 48 in CD4% for the tenofovir DF and placebo groups are different (two-sided).p-value: 0.63Van Elteren test
Secondary
Change From Baseline to Week 48 in HIV-1 RNA
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir DF | Change From Baseline to Week 48 in HIV-1 RNA | -0.97 log10 copies/mL |
| Placebo | Change From Baseline to Week 48 in HIV-1 RNA | -1.53 log10 copies/mL |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Change From Baseline to Week 48 in HIV-1 RNA | 0.0 log10 copies/mL |
| Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL | Change From Baseline to Week 48 in HIV-1 RNA | 0.2 log10 copies/mL |
Comparison: Null hypothesis: Changes from baseline through Week 48 in plasma HIV-1 RNA for the tenofovir DF and placebo groups are equal. Alternative hypothesis: Changes from baseline through Week 48 in plasma HIV-1 RNA for the tenofovir DF and placebo groups are different (two-sided).p-value: 0.37Van Elteren test
Secondary
Change From Baseline to Week 96 in CD4 Count
Time frame: Baseline to 96 weeks
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir DF | Change From Baseline to Week 96 in CD4 Count | 152 cells/mm3 |
| Placebo | Change From Baseline to Week 96 in CD4 Count | -6 cells/mm3 |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Change From Baseline to Week 96 in CD4 Count | -69 cells/mm3 |
Secondary
Change From Baseline to Week 96 in CD4 Percentage
CD4 percentage is the percentage of total lymphocytes that are CD4 cells.
Time frame: Baseline to 96 weeks
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir DF | Change From Baseline to Week 96 in CD4 Percentage | 5.0 Percentage of CD4 lymphocytes |
| Placebo | Change From Baseline to Week 96 in CD4 Percentage | 2.0 Percentage of CD4 lymphocytes |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Change From Baseline to Week 96 in CD4 Percentage | 9.0 Percentage of CD4 lymphocytes |
Secondary
Change From Baseline to Week 96 in HIV-1 RNA
Time frame: Baseline to 96 weeks
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir DF | Change From Baseline to Week 96 in HIV-1 RNA | -2.1 log10 copies/mL |
| Placebo | Change From Baseline to Week 96 in HIV-1 RNA | 0.0 log10 copies/mL |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Change From Baseline to Week 96 in HIV-1 RNA | 0.1 log10 copies/mL |
Secondary
Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 144
Time frame: Baseline to 144 weeks
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 144 | 90.0 Percentage of participants |
| Placebo | Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 144 | 0 Percentage of participants |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 144 | 0 Percentage of participants |
Secondary
Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 192
Time frame: Baseline to 192 weeks
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 192 | 71.4 Percentage of participants |
| Placebo | Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 192 | 0 Percentage of participants |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 192 | 50.0 Percentage of participants |
Secondary
Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 24
Time frame: Baseline to 24 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 24 | 56.8 Percentage of participants |
| Placebo | Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 24 | 51.2 Percentage of participants |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 24 | 0 Percentage of participants |
| Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL | Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 24 | 12.5 Percentage of participants |
Comparison: Null hypothesis: Percentage of participants who had at least a 1.0 log10 copies/mL decrease from baseline to Week 24 in HIV-1 RNA for the tenofovir DF and placebo groups is equal. Alternative hypothesis: Percentage of participants who had at least a 1.0 log10 copies/mL decrease from baseline to Week 24 in HIV-1 RNA for the tenofovir DF and placebo groups is different (two-sided).p-value: 0.67Fisher Exact
Secondary
Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 240
Time frame: Baseline to 240 weeks
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 240 | 100.0 Percentage of participants |
| Placebo | Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 240 | 0 Percentage of participants |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 240 | 100.0 Percentage of participants |
Secondary
Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0log 10 Copies/mL From Baseline to Week 288
Time frame: Baseline to 288 weeks
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0log 10 Copies/mL From Baseline to Week 288 | 100.0 Percentage of participants |
| Placebo | Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0log 10 Copies/mL From Baseline to Week 288 | 0 Percentage of participants |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0log 10 Copies/mL From Baseline to Week 288 | 0 Percentage of participants |
Secondary
Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 336
No analysis was performed because the last study participant discontinued after Week 294 and the study was closed.
Time frame: Baseline to 336 weeks
Population: ITT Analysis Set, missing = excluded method
Secondary
Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 48
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 48 | 47.7 Percentage of participants |
| Placebo | Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 48 | 53.7 Percentage of participants |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 48 | 0 Percentage of participants |
| Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL | Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 48 | 0 Percentage of participants |
Comparison: Null hypothesis: Percentage of participants who had at least a 1.0 log10 copies/mL decrease from baseline to Week 48 in HIV-1 RNA for the tenofovir DF and placebo groups is equal. Alternative hypothesis: Percentage of participants who had at least a 1.0 log10 copies/mL decrease from baseline to Week 48 in HIV-1 RNA for the tenofovir DF and placebo groups is different (two-sided).p-value: 0.67Fisher Exact
Secondary
Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 96
Time frame: Baseline to 96 weeks
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 96 | 73.7 Percentage of participants |
| Placebo | Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 96 | 5.9 Percentage of participants |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Percentage of Participants With an HIV-1 RNA Decrease of ≥ 1.0 log10 Copies/mL From Baseline to Week 96 | 33.3 Percentage of participants |
Secondary
Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 144
Time frame: Week 144
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 144 | 70.0 Percentage of participants |
| Placebo | Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 144 | 72.7 Percentage of participants |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 144 | 0 Percentage of participants |
Secondary
Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 192
Time frame: Week 192
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 192 | 57.1 Percentage of participants |
| Placebo | Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 192 | 80.0 Percentage of participants |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 192 | 50.0 Percentage of participants |
Secondary
Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 24
Time frame: Week 24
Population: ITT Analysis Set. The Tenofovir DF and Placebo groups were analyzed using the missing = failure method in which participants with missing data were considered to have failed to achieve the endpoint. The Placebo/TDF groups were analyzed using the missing = excluded method.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 24 | 40.9 Percentage of participants |
| Placebo | Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 24 | 41.5 Percentage of participants |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 24 | 83.3 Percentage of participants |
| Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL | Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 24 | 6.3 Percentage of participants |
Comparison: Null hypothesis: Percentage of participants with HIV-1 RNA \< 400 copies/mL at Week 24 for the tenofovir DF and placebo groups is equal. Alternative hypothesis: Percentage of participants with HIV-1 RNA \< 400 copies/mL at Week 24 for the tenofovir DF and placebo groups is different (two-sided).p-value: 1Fisher Exact
Secondary
Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 240
Time frame: Week 240
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 240 | 75.0 Percentage of participants |
| Placebo | Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 240 | 100.0 Percentage of participants |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 240 | 100.0 Percentage of participants |
Secondary
Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 288
Time frame: Week 288
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 288 | 0 Percentage of participants |
| Placebo | Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 288 | 100.0 Percentage of participants |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 288 | 0 Percentage of participants |
Secondary
Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 336
No analysis was performed because the last study participant discontinued after Week 294 and the study was closed.
Time frame: Week 336
Population: ITT Analysis Set, missing = excluded method
Secondary
Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 48
Time frame: Week 48
Population: ITT Analysis Set. The Tenofovir DF and Placebo groups were analyzed using the missing = failure method. The Placebo/TDF groups were analyzed using the missing = excluded method.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 48 | 34.1 Percentage of participants |
| Placebo | Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 48 | 43.9 Percentage of participants |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 48 | 77.8 Percentage of participants |
| Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL | Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 48 | 0 Percentage of participants |
Comparison: Null hypothesis: Percentage of participants with HIV-1 RNA \< 400 copies/mL at Week 48 for the tenofovir DF and placebo groups is equal. Alternative hypothesis: Percentage of participants with HIV-1 RNA \< 400 copies/mL at Week 48 for the tenofovir DF and placebo groups is different (two-sided).p-value: 0.38Fisher Exact
Secondary
Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 96
Time frame: Week 96
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 96 | 63.2 Percentage of participants |
| Placebo | Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 96 | 70.6 Percentage of participants |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 96 | 33.3 Percentage of participants |
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 144
Time frame: Week 144
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 144 | 70.0 Percentage of participants |
| Placebo | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 144 | 45.5 Percentage of participants |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 144 | 0 Percentage of participants |
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 192
Time frame: Week 192
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 192 | 42.9 Percentage of participants |
| Placebo | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 192 | 60.0 Percentage of participants |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 192 | 50.0 Percentage of participants |
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24
Time frame: Week 24
Population: ITT Analysis Set. The Tenofovir DF and Placebo groups were analyzed using the missing = failure method. The Placebo/TDF groups were analyzed using the missing = excluded method.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 | 20.5 Percentage of participants |
| Placebo | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 | 34.1 Percentage of participants |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 | 77.8 Percentage of participants |
| Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 | 0 Percentage of participants |
Comparison: Null hypothesis: Percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 24 for the tenofovir DF and placebo groups is equal. Alternative hypothesis: Percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 24 for the tenofovir DF and placebo groups is different (two-sided).p-value: 0.22Fisher Exact
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 240
Time frame: Week 240
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 240 | 75.0 Percentage of participants |
| Placebo | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 240 | 100.0 Percentage of participants |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 240 | 100.0 Percentage of participants |
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 288
Time frame: Week 288
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 288 | 0 Percentage of participants |
| Placebo | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 288 | 100.0 Percentage of participants |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 288 | 0 Percentage of participants |
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 336
No analysis was performed because the last study participant discontinued after Week 294 and the study was closed.
Time frame: Week 336
Population: ITT Analysis Set, missing = excluded method
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48
Time frame: Week 48
Population: ITT Analysis Set. The Tenofovir DF and Placebo groups were analyzed using the missing = failure method. The Placebo/TDF groups were analyzed using the missing = excluded method.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 | 27.3 Percentage of participants |
| Placebo | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 | 36.6 Percentage of participants |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 | 61.1 Percentage of participants |
| Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 | 0 Percentage of participants |
Comparison: Null hypothesis: Percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 for the tenofovir DF and placebo groups is equal. Alternative hypothesis: Percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 for the tenofovir DF and placebo groups is different (two-sided).p-value: 0.48Fisher Exact
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96
Time frame: Week 96
Population: ITT Analysis Set, missing = excluded method
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 | 47.4 Percentage of participants |
| Placebo | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 | 58.8 Percentage of participants |
| Placebo/TDF, HIV-1 RNA < 1000 Copies/mL | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 | 33.3 Percentage of participants |
Secondary
Percentage of Participants With Virologic Failure Through Week 48
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tenofovir DF | Percentage of Participants With Virologic Failure Through Week 48 | 51 Kaplan-Meier percentage |
| Placebo | Percentage of Participants With Virologic Failure Through Week 48 | 39 Kaplan-Meier percentage |
Comparison: Null hypothesis: The survival functions for the tenofovir DF and placebo groups up to Week 48 are equal. Alternative hypothesis: The survival functions for the tenofovir DF and placebo groups up to Week 48 are different (two-sided).p-value: 0.29Log Rank
Secondary
Time-weighted Average Change From Baseline Through Week 48 (DAVG48) in Plasma HIV-1 RNA
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).
Time frame: Baseline to 48 weeks
Population: ITT Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tenofovir DF | Time-weighted Average Change From Baseline Through Week 48 (DAVG48) in Plasma HIV-1 RNA | -1.423 log10 copies/mL |
| Placebo | Time-weighted Average Change From Baseline Through Week 48 (DAVG48) in Plasma HIV-1 RNA | -1.352 log10 copies/mL |
Comparison: Null hypothesis: Time-weighted average changes from baseline through Week 48 in plasma HIV-1 RNA for the tenofovir DF and placebo groups are equal. Alternative hypothesis: Time-weighted average changes from baseline through Week 48 in plasma HIV-1 RNA for the tenofovir DF and placebo groups are different (two-sided).p-value: 0.4Van Elteren test