HIV-1, HIV Infections
Conditions
Keywords
Antiretroviral, HIV-1, AIDS, TMC278-C215, TMC278-TiDP6-C215, 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 background regimen containing 2 nucleoside/nucleotide reverse transcriptase inhibitors ( investigator choice of ABC/3TC, TDF/FTC or AZT/3TC) 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 and 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 (like tossing a coin) to TMC278 or to efavirenz in combination with two other anti-HIV drugs of the class nucleoside/nucleotide reverse transcriptase inhibitors. 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 daily; plus efavirenz (EFV) placebo; plus 2 nucleoside/nucleotide reverse transcriptase inhibitors; Control Group: One tablet of Placebo daily that looks just like TMC278 plus EFV 600 mg daily plus 2 nucleoside/nucleotide reverse transcriptase inhibitors for 104 weeks.
Interventions
DRUGTMC278
25 mg tablet once daily for 96 weeks
DRUGefavirenz
600 mg tablet 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 the 2 nucleoside/nucleotide reverse transcriptase inhibitors chosen for treatment * Patient agrees not to start ART before the baseline visit * Patient is HLA-B\*5701 negative in case abacavir is included in the patient's treatment regimen.
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 Per 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 Per mL) at Week 96 | Week 96 | — |
| Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per 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 18 months for TMC278 and 12 months for Efavirenz | 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 post-Week 96 visit. |
| Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per 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 Wk 48 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 Per mL) at Week 96 | Week 96 | Virological response is defined as confirmed plasma viral load \< 400 HIV-1 (RNA) copies/mL at Week 96. 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 \>= 400 copies/mL after being responder) or who were never suppressed (no confirmed viral load \<400 copies/mL). |
| 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 Determinations by Developing 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 Per mL) at Week 48 | Week 48 | Virological response is defined as confirmed plasma viral load \< 400 HIV-1 (RNA) copies/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 \>= 400 copies/mL after being responder) or who were never suppressed (no confirmed viral load \<400 copies/mL). |
Countries
Australia, Belgium, Brazil, Canada, Chile, China, Costa Rica, France, Germany, India, Mexico, Panama, Portugal, Puerto Rico, Russia, South Africa, Spain, Thailand, United Kingdom, United States
Participant flow
Recruitment details
A phase III, randomized, double-blind trial of TMC278 25 mg q.d. versus efavirenz 600mg q.d. in combination with a background regimen containing 2 nucleoside/nucleotide reverse transcriptase inhibitors in antiretroviral-naïve HIV-1 infected subjects
Pre-assignment details
680 participants were randomized (340 in TMC 278 and 340 in efavirenz) but only 338 participants were treated with efavirenz (2 were randomized but not treated).
Participants by arm
| Arm | Count |
|---|---|
| TMC278 25 mg tablet once daily | 340 |
| Efavirenz 600 mg once daily | 338 |
| Total | 678 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 18 | 27 |
| Overall Study | Lost to Follow-up | 15 | 11 |
| Overall Study | Other | 3 | 3 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Sponsor's Decision | 0 | 1 |
| Overall Study | Subject Ineligible To Continue The Trial | 2 | 0 |
| Overall Study | Subject Non-Compliant | 4 | 4 |
| Overall Study | Subject Reached A Virologic Endpoint | 22 | 14 |
| Overall Study | Withdrawal by Subject | 4 | 13 |
Baseline characteristics
| Characteristic | TMC278 | Efavirenz | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 339 Participants | 337 Participants | 676 Participants |
| Age, Continuous | 36.7 years STANDARD_DEVIATION 9.39 | 36.4 years STANDARD_DEVIATION 8.92 | 36.5 years STANDARD_DEVIATION 9.15 |
| Region Enroll Africa | 19 participants | 38 participants | 57 participants |
| Region Enroll Asia | 59 participants | 61 participants | 120 participants |
| Region Enroll Latin America | 90 participants | 85 participants | 175 participants |
| Region Enroll USA, Canada, Europe, Australia | 172 participants | 154 participants | 326 participants |
| Sex: Female, Male Female | 90 Participants | 94 Participants | 184 Participants |
| Sex: Female, Male Male | 250 Participants | 244 Participants | 494 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 253 / 340 | 259 / 338 |
| serious Total, serious adverse events | 32 / 340 | 31 / 338 |
Outcome results
Primary
Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies Per 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 Intent-to-Treat 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 Per mL) at Week 48 | Responder | 291 Participants |
| TMC278 | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies Per mL) at Week 48 | Discontinued due to other reason than AE | 16 Participants |
| TMC278 | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies Per mL) at Week 48 | Virologic failure | 24 Participants |
| TMC278 | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies Per mL) at Week 48 | Death | 1 Participants |
| TMC278 | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies Per mL) at Week 48 | Discontinued due to AE | 8 Participants |
| Efavirenz | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies Per mL) at Week 48 | Responder | 276 Participants |
| Efavirenz | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies Per mL) at Week 48 | Death | 3 Participants |
| Efavirenz | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies Per mL) at Week 48 | Discontinued due to AE | 21 Participants |
| Efavirenz | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies Per mL) at Week 48 | Virologic failure | 18 Participants |
| Efavirenz | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies Per mL) at Week 48 | Discontinued due to other reason than AE | 20 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: [-1.6, 9]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 Intent-to-Treat analysis set was considered the primary efficacy analysis set.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 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 | 188.6 cells per microliter |
| 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 | 234.5 cells per microliter |
| 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 | 8.3 cells per microliter |
| 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 |
| 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 | 212.0 cells per microliter |
| 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 | 9.7 cells per microliter |
| 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 | 170.7 cells per microliter |
| 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 | 8.0 cells per microliter |
Secondary
Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per 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 Wk 48 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 Intent-to-Treat analysis set was considered the primary efficacy analysis set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TMC278 | Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per mL) at Week 48 | Virologic Response (<50 copies/mL) | 281 Participants |
| TMC278 | Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per mL) at Week 48 | Virologic failure | 41 Participants |
| TMC278 | Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per mL) at Week 48 | No plasma viral load data in 48-week window | 18 Participants |
| Efavirenz | Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per mL) at Week 48 | Virologic failure | 38 Participants |
| Efavirenz | Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per mL) at Week 48 | No plasma viral load data in 48-week window | 35 Participants |
| Efavirenz | Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per mL) at Week 48 | Virologic Response (<50 copies/mL) | 265 Participants |
p-value: <0.000195% CI: [-1.9, 9.6]Regression, Logistic
Secondary
Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per 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 | Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per mL) at Week 96 | Virologic response (<50 copies/mL) | 259 Participants |
| TMC278 | Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per mL) at Week 96 | Virologic failure | 53 Participants |
| TMC278 | Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per mL) at Week 96 | No plasma viral load data in 96-Week window | 28 Participants |
| Efavirenz | Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per mL) at Week 96 | Virologic response (<50 copies/mL) | 254 Participants |
| Efavirenz | Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per mL) at Week 96 | Virologic failure | 38 Participants |
| Efavirenz | Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per mL) at Week 96 | No plasma viral load data in 96-Week window | 46 Participants |
p-value: <0.000195% CI: [-5.6, 7]Regression, Logistic
Secondary
Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies Per mL) at Week 48
Virological response is defined as confirmed plasma viral load \< 400 HIV-1 (RNA) copies/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 \>= 400 copies/mL after being responder) or who were never suppressed (no confirmed viral load \<400 copies/mL).
Time frame: Week 48
Population: The Intent-to-Treat 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 Per mL) at Week 48 | 300 Participants |
| Efavirenz | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies Per mL) at Week 48 | 286 Participants |
Secondary
Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies Per mL) at Week 96
Virological response is defined as confirmed plasma viral load \< 400 HIV-1 (RNA) copies/mL at Week 96. 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 \>= 400 copies/mL after being responder) or who were never suppressed (no confirmed viral load \<400 copies/mL).
Time frame: Week 96
Population: The Intent-to-Treat 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 Per mL) at Week 96 | 283 Participants |
| Efavirenz | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies Per mL) at Week 96 | 270 Participants |
Secondary
Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies Per 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 | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies Per mL) at Week 96 | Virologic failure | 34 Participants |
| TMC278 | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies Per mL) at Week 96 | Discontinued due to AE | 16 Participants |
| TMC278 | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies Per mL) at Week 96 | Death | 1 Participants |
| TMC278 | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies Per mL) at Week 96 | Discontinued due to other reason than AE | 20 Participants |
| TMC278 | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies Per mL) at Week 96 | Responder | 269 Participants |
| Efavirenz | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies Per mL) at Week 96 | Discontinued due to other reason than AE | 30 Participants |
| Efavirenz | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies Per mL) at Week 96 | Responder | 258 Participants |
| Efavirenz | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies Per mL) at Week 96 | Virologic failure | 24 Participants |
| Efavirenz | Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies Per 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 Per mL) at Week 96 | Discontinued due to AE | 23 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: [-3.6, 8.4]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 post-Week 96 visit.
Time frame: Variable, ranging from 3 months up to maximum 18 months for TMC278 and 12 months for Efavirenz
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). | 260 Participants |
| Efavirenz | Number of Participants With Virological Response (Observed, <50 Copies/mL) at Last On-Treatment Visit (Post-Week 96). | 246 Participants |
Secondary
Number of Participants With Virologic Failure for the Resistance Determinations by Developing 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 Intent-to-Treat 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TMC278 | Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure | K101E | 3 Participants |
| TMC278 | Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure | V189I | 2 Participants |
| TMC278 | Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure | Y188C | 0 Participants |
| TMC278 | Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure | K103N | 0 Participants |
| TMC278 | Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure | Treatment-emergent N(t)RTI RAM | 17 Participants |
| TMC278 | Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure | H221Y | 3 Participants |
| TMC278 | Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure | K65R | 0 Participants |
| TMC278 | Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure | K219E | 2 Participants |
| TMC278 | Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure | V90I | 2 Participants |
| TMC278 | Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure | M184I | 8 Participants |
| TMC278 | Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure | E138K | 13 Participants |
| TMC278 | Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure | M184V | 10 Participants |
| TMC278 | Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure | V106M | 0 Participants |
| TMC278 | Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure | Treatment-emergent NNRTI RAM | 17 Participants |
| Efavirenz | Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure | Treatment-emergent NNRTI RAM | 11 Participants |
| Efavirenz | Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure | K65R | 2 Participants |
| Efavirenz | Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure | E138K | 1 Participants |
| Efavirenz | Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure | H221Y | 0 Participants |
| Efavirenz | Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure | K101E | 2 Participants |
| Efavirenz | Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure | K103N | 6 Participants |
| Efavirenz | Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure | V90I | 1 Participants |
| Efavirenz | Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure | V106M | 2 Participants |
| Efavirenz | Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure | V189I | 0 Participants |
| Efavirenz | Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure | Y188C | 2 Participants |
| Efavirenz | Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure | Treatment-emergent N(t)RTI RAM | 6 Participants |
| Efavirenz | Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure | K219E | 0 Participants |
| Efavirenz | Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure | M184I | 1 Participants |
| Efavirenz | Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure | M184V | 3 Participants |