A Phase 2B Multicenter, Randomized, Comparative Trial Of UK-453,061 Versus Etravirine In Combination With Darunavir/Ritonavir And A Nucleos(t)Ide Reverse Transcriptase Inhibitor For The Treatment Of Antiretroviral Experienced HIV-1 Infected Subjects With Evidence Of NNRTI Resistant HIV-1

Plasma HIV-1 RNA level was determined by the Roche Amplicor HIV-1 Monitor standard assay (version 1.5).

Time frame: Week 24

Population: ITT population. Participants who died, discontinued, lost to follow-up, switched/changed dose of anti-retro viral (ARV) drug not allowed by protocol, had missing plasma HIV-1 RNA data at 24 weeks were considered to have plasma HIV-1 RNA \>=50 copies/mL and were referred to as failure.

Blood samples for immunological status assessed by CD4+ lymphocyte count. Baseline value was calculated as the average of the measurements collected prior to and including Day 1 pre-dose.

Time frame: Baseline, Week 24, 48, 96

Population: ITT population included all randomized participants who received at least 1 dose of study drug. Missing values were imputed using LOCF. Participants with missing baseline or no CD4+ count available on treatment imputed as no or zero change from baseline.

Blood samples for immunological status assessed by CD4+ lymphocyte count. Baseline value was calculated as the average of the measurements collected prior to and including Day 1 pre-dose.

Time frame: Baseline, Week 24, 48, 96

Population: ITT population included all randomized participants who received at least 1 dose of study drug. Missing values were imputed using LOCF. Participants with missing baseline or no CD4+ count available on treatment imputed as no or zero change from baseline.

Plasma HIV-1 RNA level was determined by the Roche Amplicor HIV-1 Monitor standard assay (version 1.5). For the log10 scale, all the HIV-1 RNA levels were log10 transformed prior to the average calculations. Baseline value calculated as average of measurements collected prior to and including Day 1 pre-dose.

Time frame: Baseline, Week 24, 48, 96

Population: ITT population. Participant discontinued before a visit of interest: value imputed as zero; not discontinued but observation is missing: last observation carried forward (LOCF) imputation used; missing baseline or no HIV-1 RNA level assessment: value imputed as zero.

Simple quartile exposure analysis of success rate (viral load \<50 copies/mL) versus median Cmin assesses the exposure response relationship. Percentage of participants with HIV-1 RNA level \<50 copies/mL at median Cmin quartile were planned to be reported.

Time frame: Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48

Population: Due to the sparsity of the data, the ability to interpret the pharmacokinetic/pharmacodynamic (PK/PD) results was limited, thus the data was not reported.

Laboratory analysis included blood chemistry, hematology and urinalysis.

Time frame: Baseline up to Week 48 or early termination

Population: Safety analysis set included all randomized participants who received at least 1 dose of study medication. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Genotypic and phenotypic resistance to NNRTIs based on International Acquired Immunodeficiency Syndrome (AIDS) Society, United States of America (IAS-USA) RAM guidelines were evaluated using Monogram Biosciences PhenoSenseGT Assay at Baseline. This was then repeated for all participants with HIV-1 viral load \>500 copies/mL at treatment failure, up to Week 48.

Time frame: Baseline through Week 48

Population: Virology analysis set included a subset of participants from TLOVR50 failures who had valid genotypic or phenotypic susceptibility testing result and with plasma HIV-1 RNA \>500 copies/mL at baseline and treatment failure.

Plasma HIV-1 RNA level was determined by the Roche Amplicor HIV-1 Monitor standard assay (version 1.5).

Time frame: Week 24, 48, 96

Population: ITT population. Participants who died,discontinued,lost to follow-up,switched/changed dose of ARV drug not allowed by protocol,had missing plasma HIV-1 RNA data at 24, 48, 96 weeks were considered to have plasma HIV-1 RNA \>=400 copies/mL and referred to as failure. n=participants evaluable at specified time point for each arm group, respectively.

Plasma HIV-1 RNA level was determined by the Roche Amplicor HIV-1 Monitor standard assay (version 1.5).

Time frame: Weeks 48, 96

Population: ITT population. Participants who died, discontinued,lost to follow-up,switched/changed dose of ARV drug not allowed by protocol,had missing plasma HIV-1 RNA data at 48, 96 weeks were considered to have plasma HIV-1 RNA \>=50 copies/mL and were referred to as failure. n=participants evaluable at specified time point for each arm group, respectively.

TLOVR50 response (50 denotes lower limit of quantification \[LLOQ\] of assay=50 copies/mL): compliment to TLOVR50 failure. TLOVR50 failure based on observed HIV-1 RNA levels and failure events (death; permanent discontinuation of drug; lost to follow-up; new ARV drug; met treatment failure \[TF\] criteria). TF: an increase of at least (\>=)3 times the baseline plasma HIV-1 RNA level at Week 2 or thereafter; failure to achieve HIV-1 RNA level \<50 copies/mL at Week 24; starting at Week 2, an increase in HIV-1 RNA level to detectable levels (\>50 copies/mL); HIV-1 RNA \<1 log10 decrease from baseline at Week 4 or thereafter. TF were confirmed by second measurement \>=14 days after first. Baseline value was calculated as the average of the measurements collected prior to and including Day 1 pre-dose.

Time frame: Week 24, 48, 96

Population: ITT.Participants who died,discontinued,lost to follow-up,switched/changed dose of ARV drug not allowed by protocol,had missing plasma HIV-1 RNA data at 24,48 weeks were considered to have plasma HIV-1 RNA\>=50 copies/mL;were referred as failure. Due to early termination of study,decision was made not to derive TLOVR50 responder analysis for Week 96.

Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.

Time frame: Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48

TAD was calculated as (area under the curve of HIV-1 RNA levels \[log10 copies/mL\] from baseline to the time point of interest divided by time period in weeks) minus baseline HIV-1 RNA level (log10 copies/mL). Baseline value calculated as average of measurements collected at prior to and including Day 1 pre-dose. Due to early termination of the study decision was made not to derive TAD results for Week 96.

Time frame: Week 24, 48, 96

Population: ITT population. Participant discontinued before a visit of interest: TAD imputed as zero; not discontinued but observation was missing at visit: TAD to the last non-missing timepoint; not discontinued and missing values between baseline and visit: ignore missing values; missing baseline or no HIV-1 RNA level assessment: TAD imputed as zero.