HIV-1, HIV Infections, Human Immunodeficiency Virus Type 1
Conditions
Keywords
TMC278-C209, Antiretroviral, Non-nucleoside reverse transcriptase inhibitor, HIV-1, AIDS, TMC278-TiDP6-C209, Treatment Naive
Brief summary
The purpose of this trial is to compare the effectiveness, safety and tolerability of TMC278 given at a dose of 25 mg once daily versus efavirenz (EFV) at a dose of 600 mg once daily, when combined with a fixed background regimen consisting of emtricitabine (FTC) + tenofovir disoproxil fumarate (TDF), in HIV-1 infected patients who have not yet taken any anti-HIV drugs. The following evaluations will be done: antiviral activity, immunologic changes, and viral geno-/phenotype evolution, relationship of Pharmacokinetics (PK) and PK/Pharmacodynamics, medical resource utilization and treatment adherence.
Detailed description
Over the past decade, anti-human immunodeficiency virus (HIV) drugs have been introduced sequentially for use in the clinic. Currently, patients are routinely being treated with 3 or 4 drug combinations including nucleoside/tide analogue reverse transcriptase inhibitors (NRTIs/NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and/or fusion inhibitors. New potent antiretroviral (ARV) compounds that work in people whose HIV-1 virus is resistant to available drugs are urgently needed. This is a Phase III, randomized (study medication is assigned by chance), double-blind (neither the study physician nor the patient knows the name of the study assigned medication), double-dummy, active-controlled trial to compare the effectiveness, safety, and ability to tolerate TMC278 versus efavirenz (EFV). The study will last for 104 weeks which includes a screening period of 4 weeks, a 96-week treatment period, followed by a 4 week follow-up period. Patients will be randomly assigned to TMC278 or to efavirenz, either of these treatments will be in combination with two other anti-HIV drugs (2 NRTIs: emtricitabine (FTC) + tenofovir (TDF)). TDF/FTC will be administered as a fixed dose combination if available. The hypothesis to be provided in this study is that the investigational drug TMC278 will perform just like efavirenz (EFV) in terms of antiviral effectiveness (i.e., suppressing of the plasma viral load to a level \< 50 HIV-1 RNA (ribonucleic acid) copies/mL) in ARV-naïve HIV-infected patients. During the trial, patients' health will be monitored by physical examination, interview to assess health and well being, and laboratory testing on blood and urine samples. Experimental Group: One tablet of TMC278 25 mg once daily plus one tablet of placebo once daily that looks just like efavirenz (EFV) plus tenofovir/emtricitabine; Control Group: One tablet of Placebo once daily that looks just like TMC278 plus EFV 600 mg once daily plus tenofovir/emtricitabine.
Interventions
DRUGTMC278
25 mg tablet once daily for 96 weeks
DRUGEfavirenz
600mg once daily for 96 weeks
Sponsors
Tibotec Pharmaceuticals, Ireland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Patient with documented HIV-1 infection * Patient has never been treated with a therapeutic HIV vaccine or an ARV drug prior to screening * Patient's HIV-1 plasma viral load at screening is \> 5,000 HIV-1 RNA copies/mL (assayed by RNA PCR standard specimen procedure) * Patient's virus is sensitive to TDF and FTC * Patient agrees not to start ART (antiretroviral treatment) before the baseline visit
Exclusion criteria
* Previous use of ANY ARV drug for ANY length of time * Any documented evidence of NNRTI resistance associated mutations in patient's HIV * Category C AIDS defining illness, except: stable Kaposi Sarcoma, wasting syndrome if not progressive * Pneumocystis carinii pneumonia (PCP) that is considered not cured * Active TB * Allergy or hypersensitivity to study or background ARTs * Specific grade 3 or 4 toxicity * Kidney impairment: calculated creatinine clearance \<50 ml/min
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 48 | Week 48 | Virological response is defined as confirmed plasma viral load less than (\<) 50 human immunodeficiency virus-1 (HIV-1) (ribonucleic acid \[RNA\]) copies/milliliter (ml) at Week 48. The TLOVR algorithm was used to derive response. Response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders after discontinuation. Resuppression after confirmed virologic failure was considered as failure. Virologic Failure includes participants who were rebounder (confirmed viral load \>= 50 copies/ml after being responder) or who were never suppressed (no confirmed viral load \<50 copies/ml). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 96 | Week 96 | — |
| The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 96 | Week 96 | — |
| Number of Participants With Virological Response (Observed, <50 Copies/ml) at Last On-Treatment Visit (Post-Week 96). | Variable, ranging from 3 months up to maximum 15 months for TMC278 and 12 months for Efavirenz after the 96-week visit | Virological response is defined as (observed) plasma viral load less than 50 human immunodeficiency virus-type 1 (HIV-1) ribonucleic acid (RNA) copies per ml at the last on-treatment visit (post-Week 96). |
| The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 48 | Week 48 | The analysis is based on the last observed viral load (VL) data within the Week 48 window. Virologic response is defined as a VL\<50 copies/ml (observed case). Missing VL was considered as non-response. Virologic Failure includes subjects who had VL\>=50 copies/ml in the Wk48 window, subjects who discontinued early due to lack or loss of efficacy, subjects who discontinued for reasons other than an adverse event, death or lack or loss of efficacy and at the time of discontinuation had a VL\>=50 copies/ml and subjects who had a switch in background regimen that was not permitted by the protocol. |
| Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies/ml) at Week 96 | Week 96 | — |
| Mean Change From Baseline to Week 48 and Week 96 in Absolute and Relative CD4+ Cell Counts (Using Imputed Data) | Baseline, Week 48, and Week 96 | Change from baseline in CD4+ cell count was imputed in case of missing values: in case of premature discontinuation, data were imputed with the baseline value after discontinuation (i.e. change=0, Non-Completer \[NC\] = Failure); otherwise last observation carried forward was applied. |
| Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure | Week 96 | Virologic failure for the resistance determinations was defined as lack of virologic response (never having had 2 consecutive plasma viral load \<50 copies/mL) and plasma viral load increase of \>=0.5 log 10 copies/mL above nadir (i.e., never suppressed), or confirmed loss of virologic response (2 consecutive plasma viral load \>=50 copies/mL after having had 2 consecutive plasma viral load \<50 copies/mL; i.e., rebounder), or discontinued with a last observed on-treatment plasma viral load \>=50 copies/mL after having had 2 consecutive plasma viral load \<50 copies/mL. For this study, treatment-emergent reverse transcriptase (RT) resistance associated mutations (RAMs) occurring in at least 2 virologic failures (for at least one treatment group) for the following lists are presented: i) Extended list of Non-nucleoside reverse transcriptase inhibitor (NNRTI RAMs) ii) IAS-USA list of Nucleoside/tide reverse transcriptase inhibitor (N\[t\]RTI RAMs). |
| Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies/ml) at Week 48 | Week 48 | — |
Countries
Argentina, Australia, Austria, Brazil, Canada, Denmark, France, Mexico, Netherlands, Portugal, Puerto Rico, Romania, Russia, South Africa, Spain, Sweden, Taiwan, Thailand, United Kingdom, United States
Participant flow
Recruitment details
One hundred and twelve sites in 21 countries randomized participants. In total, 694 participants were randomized: four participants did not start treatment and 690 participants started treatment (346 in the TMC278 group and 344 in the efavirenz \[control \] group).
Participants by arm
| Arm | Count |
|---|---|
| TMC278 25 milligram (mg) tablet once daily for 96 weeks. | 346 |
| Efavirenz 600 mg once daily for 96 weeks. | 344 |
| Total | 690 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 12 | 32 |
| Overall Study | Lost to Follow-up | 19 | 17 |
| Overall Study | Other | 1 | 4 |
| Overall Study | Sponsor's Decision | 1 | 1 |
| Overall Study | Subject Ineligible To Continue The Trial | 2 | 1 |
| Overall Study | Subject Non-Compliant | 7 | 5 |
| Overall Study | Subject Reached A Virologic Endpoint | 32 | 8 |
| Overall Study | Withdrawal by Subject | 10 | 10 |
Baseline characteristics
| Characteristic | TMC278 | Efavirenz | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical >=65 years | 2 Participants | 1 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 343 Participants | 343 Participants | 686 Participants |
| Age, Continuous | 37 years STANDARD_DEVIATION 9.68 | 36.7 years STANDARD_DEVIATION 9.51 | 36.8 years STANDARD_DEVIATION 9.59 |
| Region Enroll Africa | 32 participants | 31 participants | 63 participants |
| Region Enroll Asia | 47 participants | 51 participants | 98 participants |
| Region Enroll Latin America | 60 participants | 69 participants | 129 participants |
| Region Enroll USA, Canada, Europe, Australia | 207 participants | 193 participants | 400 participants |
| Sex: Female, Male Female | 78 Participants | 69 Participants | 147 Participants |
| Sex: Female, Male Male | 268 Participants | 275 Participants | 543 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 231 / 346 | 268 / 344 |
| serious Total, serious adverse events | 40 / 346 | 43 / 344 |
Outcome results
Primary
Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 48
Virological response is defined as confirmed plasma viral load less than (\<) 50 human immunodeficiency virus-1 (HIV-1) (ribonucleic acid \[RNA\]) copies/milliliter (ml) at Week 48. The TLOVR algorithm was used to derive response. Response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders after discontinuation. Resuppression after confirmed virologic failure was considered as failure. Virologic Failure includes participants who were rebounder (confirmed viral load \>= 50 copies/ml after being responder) or who were never suppressed (no confirmed viral load \<50 copies/ml).
Time frame: Week 48
Population: The ITT analysis set was considered the primary efficacy analysis set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TMC278 | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 48 | Discontinued due to Adverse Event (AE) | 6 Participants |
| TMC278 | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 48 | Responder | 287 Participants |
| TMC278 | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 48 | Virologic failure | 38 Participants |
| TMC278 | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 48 | Discontinued due to other reason than AE | 15 Participants |
| Efavirenz | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 48 | Virologic failure | 15 Participants |
| Efavirenz | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 48 | Discontinued due to Adverse Event (AE) | 25 Participants |
| Efavirenz | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 48 | Discontinued due to other reason than AE | 19 Participants |
| Efavirenz | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 48 | Responder | 285 Participants |
Comparison: Assuming a response rate of 75% at 48 weeks for both treatment groups, 340 subjects were needed per treatment (TMC278 or EFV) to establish non-inferiority of TMC278 versus EFV with a maximum allowable difference of 12% and a 1-sided significance level of 2.5%, to yield 95% power.p-value: <0.000195% CI: [-5.9, 5.2]Regression, Logistic
Secondary
Mean Change From Baseline to Week 48 and Week 96 in Absolute and Relative CD4+ Cell Counts (Using Imputed Data)
Change from baseline in CD4+ cell count was imputed in case of missing values: in case of premature discontinuation, data were imputed with the baseline value after discontinuation (i.e. change=0, Non-Completer \[NC\] = Failure); otherwise last observation carried forward was applied.
Time frame: Baseline, Week 48, and Week 96
Population: The ITT analysis set was considered the primary efficacy analysis set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TMC278 | Mean Change From Baseline to Week 48 and Week 96 in Absolute and Relative CD4+ Cell Counts (Using Imputed Data) | Absolute cell count, Week 48 | 195.5 cells per microliter | Standard Deviation 151.7 |
| TMC278 | Mean Change From Baseline to Week 48 and Week 96 in Absolute and Relative CD4+ Cell Counts (Using Imputed Data) | Relative cell count, Week 48 | 8.6 cells per microliter | Standard Deviation 5.8 |
| TMC278 | Mean Change From Baseline to Week 48 and Week 96 in Absolute and Relative CD4+ Cell Counts (Using Imputed Data) | Relative cell count, Week 96 | 10.1 cells per microliter | Standard Deviation 7.5 |
| TMC278 | Mean Change From Baseline to Week 48 and Week 96 in Absolute and Relative CD4+ Cell Counts (Using Imputed Data) | Absolute cell count, Week 96 | 220.7 cells per microliter | Standard Deviation 167.1 |
| Efavirenz | Mean Change From Baseline to Week 48 and Week 96 in Absolute and Relative CD4+ Cell Counts (Using Imputed Data) | Relative cell count, Week 96 | 10.2 cells per microliter | Standard Deviation 7.2 |
| Efavirenz | Mean Change From Baseline to Week 48 and Week 96 in Absolute and Relative CD4+ Cell Counts (Using Imputed Data) | Relative cell count, Week 48 | 8.7 cells per microliter | Standard Deviation 6 |
| Efavirenz | Mean Change From Baseline to Week 48 and Week 96 in Absolute and Relative CD4+ Cell Counts (Using Imputed Data) | Absolute cell count, Week 96 | 226.7 cells per microliter | Standard Deviation 188.9 |
| Efavirenz | Mean Change From Baseline to Week 48 and Week 96 in Absolute and Relative CD4+ Cell Counts (Using Imputed Data) | Absolute cell count, Week 48 | 181.6 cells per microliter | Standard Deviation 156.9 |
Secondary
Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies/ml) at Week 48
Time frame: Week 48
Population: The ITT analysis set was considered the primary efficacy analysis set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TMC278 | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies/ml) at Week 48 | 297 Participants |
| Efavirenz | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies/ml) at Week 48 | 293 Participants |
Secondary
Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies/ml) at Week 96
Time frame: Week 96
Population: The ITT analysis set was considered the primary efficacy analysis set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TMC278 | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies/ml) at Week 96 | 273 Participants |
| Efavirenz | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies/ml) at Week 96 | 278 Participants |
Secondary
Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 96
Time frame: Week 96
Population: The ITT analysis set was considered the primary efficacy analysis set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TMC278 | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 96 | Virologic failure | 45 Participants |
| TMC278 | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 96 | Discontinued due to AE | 10 Participants |
| TMC278 | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 96 | Death | 0 Participants |
| TMC278 | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 96 | Discontinued due to other reason than AE | 28 Participants |
| TMC278 | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 96 | Responder | 263 Participants |
| Efavirenz | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 96 | Discontinued due to other reason than AE | 25 Participants |
| Efavirenz | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 96 | Responder | 271 Participants |
| Efavirenz | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 96 | Virologic failure | 16 Participants |
| Efavirenz | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 96 | Death | 3 Participants |
| Efavirenz | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies/ml) at Week 96 | Discontinued due to AE | 29 Participants |
p-value: 0.005595% CI: [-9.4, 3.1]Regression, Logistic
Secondary
Number of Participants With Virological Response (Observed, <50 Copies/ml) at Last On-Treatment Visit (Post-Week 96).
Virological response is defined as (observed) plasma viral load less than 50 human immunodeficiency virus-type 1 (HIV-1) ribonucleic acid (RNA) copies per ml at the last on-treatment visit (post-Week 96).
Time frame: Variable, ranging from 3 months up to maximum 15 months for TMC278 and 12 months for Efavirenz after the 96-week visit
Population: Participants with at least 1 Post-Week 96 visit were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TMC278 | Number of Participants With Virological Response (Observed, <50 Copies/ml) at Last On-Treatment Visit (Post-Week 96). | 245 Participants |
| Efavirenz | Number of Participants With Virological Response (Observed, <50 Copies/ml) at Last On-Treatment Visit (Post-Week 96). | 261 Participants |
Secondary
Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure
Virologic failure for the resistance determinations was defined as lack of virologic response (never having had 2 consecutive plasma viral load \<50 copies/mL) and plasma viral load increase of \>=0.5 log 10 copies/mL above nadir (i.e., never suppressed), or confirmed loss of virologic response (2 consecutive plasma viral load \>=50 copies/mL after having had 2 consecutive plasma viral load \<50 copies/mL; i.e., rebounder), or discontinued with a last observed on-treatment plasma viral load \>=50 copies/mL after having had 2 consecutive plasma viral load \<50 copies/mL. For this study, treatment-emergent reverse transcriptase (RT) resistance associated mutations (RAMs) occurring in at least 2 virologic failures (for at least one treatment group) for the following lists are presented: i) Extended list of Non-nucleoside reverse transcriptase inhibitor (NNRTI RAMs) ii) IAS-USA list of Nucleoside/tide reverse transcriptase inhibitor (N\[t\]RTI RAMs).
Time frame: Week 96
Population: The ITT analysis set was considered the primary efficacy analysis set. Here N (Number of Participants Analyzed) signifies number of Participants who were evaluable (had data) for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TMC278 | Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure | N(t)RTI RAM: K065R | 3 Participants |
| TMC278 | Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure | NNRTI RAM: K101E | 5 Participants |
| TMC278 | Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure | Any RAM from IAS-USA N(t)RTI RAMs list | 31 Participants |
| TMC278 | Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure | NNRTI RAM: Y181C | 5 Participants |
| TMC278 | Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure | N(t)RTI RAM: K219E | 3 Participants |
| TMC278 | Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure | NNRTI RAM: V90I | 4 Participants |
| TMC278 | Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure | N(t)RTI RAM: Y115F | 2 Participants |
| TMC278 | Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure | NNRTI RAM: V189I | 4 Participants |
| TMC278 | Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure | N(t)RTI RAM: M184V | 7 Participants |
| TMC278 | Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure | NNRTI RAM: H221Y | 4 Participants |
| TMC278 | Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure | Any RAM from Extended NNRTI RAMs list | 29 Participants |
| TMC278 | Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure | NNRTI RAM: E138Q | 3 Participants |
| TMC278 | Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure | N(t)RTI RAM: M184I | 24 Participants |
| TMC278 | Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure | NNRTI RAM: K103N | 1 Participants |
| TMC278 | Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure | NNRTI RAM: E138K | 18 Participants |
| Efavirenz | Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure | NNRTI RAM: K103N | 8 Participants |
| Efavirenz | Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure | Any RAM from IAS-USA N(t)RTI RAMs list | 5 Participants |
| Efavirenz | Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure | N(t)RTI RAM: M184I | 3 Participants |
| Efavirenz | Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure | N(t)RTI RAM: M184V | 3 Participants |
| Efavirenz | Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure | N(t)RTI RAM: K065R | 0 Participants |
| Efavirenz | Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure | N(t)RTI RAM: Y115F | 0 Participants |
| Efavirenz | Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure | Any RAM from Extended NNRTI RAMs list | 9 Participants |
| Efavirenz | Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure | NNRTI RAM: E138K | 0 Participants |
| Efavirenz | Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure | NNRTI RAM: K101E | 0 Participants |
| Efavirenz | Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure | NNRTI RAM: Y181C | 0 Participants |
| Efavirenz | Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure | NNRTI RAM: V90I | 0 Participants |
| Efavirenz | Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure | NNRTI RAM: V189I | 0 Participants |
| Efavirenz | Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure | NNRTI RAM: H221Y | 0 Participants |
| Efavirenz | Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure | NNRTI RAM: E138Q | 0 Participants |
| Efavirenz | Number of Participants With Virologic Failure for the Resistance Determination by Emerging Resistance Associated Mutations: First Available On-Treatment Genotypic Data After Failure | N(t)RTI RAM: K219E | 0 Participants |
Secondary
The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 48
The analysis is based on the last observed viral load (VL) data within the Week 48 window. Virologic response is defined as a VL\<50 copies/ml (observed case). Missing VL was considered as non-response. Virologic Failure includes subjects who had VL\>=50 copies/ml in the Wk48 window, subjects who discontinued early due to lack or loss of efficacy, subjects who discontinued for reasons other than an adverse event, death or lack or loss of efficacy and at the time of discontinuation had a VL\>=50 copies/ml and subjects who had a switch in background regimen that was not permitted by the protocol.
Time frame: Week 48
Population: The ITT analysis set was considered the primary efficacy analysis set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TMC278 | The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 48 | Virologic Response HIV RNA <50 copies/mL at Wk 48 | 285 Participants |
| TMC278 | The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 48 | Virologic Failure | 47 Participants |
| TMC278 | The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 48 | No Viral Load Data in 48 week window | 14 Participants |
| Efavirenz | The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 48 | Virologic Response HIV RNA <50 copies/mL at Wk 48 | 281 Participants |
| Efavirenz | The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 48 | Virologic Failure | 24 Participants |
| Efavirenz | The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 48 | No Viral Load Data in 48 week window | 39 Participants |
p-value: <0.000195% CI: [-5.4, 5.9]Regression, Logistic
Secondary
The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 96
Time frame: Week 96
Population: The Intent-to-Treat analysis set was considered the primary efficacy analysis set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TMC278 | The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 96 | No viral load data in the 96 week window | 27 Participants |
| TMC278 | The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 96 | Virologic Response, <50 copies/ml | 265 Participants |
| TMC278 | The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 96 | Virologic failure | 54 Participants |
| Efavirenz | The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 96 | Virologic Response, <50 copies/ml | 268 Participants |
| Efavirenz | The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 96 | Virologic failure | 27 Participants |
| Efavirenz | The Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies/ml) at Week 96 | No viral load data in the 96 week window | 49 Participants |
p-value: 0.001395% CI: [-8, 4.5]Regression, Logistic