HIV Attachment Inhibitor to Treat Human Immunodeficiency Virus 1 (HIV-1) Infections

Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or suspected transmission of an infectious agent via the study drug were categorized as SAE. AEs leading to discontinuation of study therapy were also reported as safety assessment. Safety population included all participants who received at least one dose of study treatment. Summaries of SAEs and AEs leading to discontinuation or withdrawal through Week 24 included AEs with onset on or after the start of study treatment (i.e. study date of first study treatment intake) up to and including the end of the Week 24 visit snapshot window.

Time frame: Up to Week 24

Population: Safety Population

Percentage of participants with plasma HIV 1 RNA \< 50 c/mL at Week 24 using the Food and Drug Administration (FDA) snapshot algorithm was assessed to evaluate the antiviral activity. Treatment comparisons were not performed as this was an estimation study. Response rates were tabulated by treatment arm with exact Clopper-Pearson binomial 95 percentage confidence intervals (CI). Virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment within the snapshot window of the visit of interest. Intent-To-Treat-Exposed (ITT-E) Population includes all randomized participants who received at least one dose of study treatment.

Time frame: Week 24

Population: ITT-E Population

Blood was collected and CD4+ cell count assessment by flow cytometery was carried out at Baseline (Day 1), Weeks 24, 48 and 96 to evaluate the immunological activity of multiple doses of BMS-663068/GSK3684934. Baseline is defined as the last non-missing value on or before the date of first dose of study treatment and those values are absolute values. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Time frame: Baseline and Weeks 24, 48 and 96

Population: ITT-E Population

Virologic failure is defined clinically as confirmed plasma HIV-1 RNA \>= 50 copies/mL at Week 24 or later or later or virologic rebound defined as confirmed HIV-1 RNA \>=50 copies/mL at any time after prior confirmed suppression to \<50 copies/mL OR confirmed \>1 log10 copies/mL increase in HIV-1 RNA at any time above nadir level where nadir was \>= 50 copies/mL. The phenotypic resistance to a drug is defined as a fold change (i.e, ratio of the IC50 of the clinical isolate to the IC50 of the reference strain) greater than the cut-off for reduced susceptibility. Maximum change from Baseline in Temsavir IC50 fold change based on all on-treatment values has been presented. Baseline is defined as the last non-missing value on or before the date of first dose of study treatment and those values are absolute values. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants available at the specified time points were analyzed.

Time frame: Baseline and up to Week 48

Population: ITT-E Resistance Tested through Week 48 Population

Virologic failure is defined clinically as confirmed plasma HIV-1 RNA \>= 50 copies/mL at Week 24 or later or virologic rebound defined as confirmed HIV-1 RNA \>=50 copies/mL at any time after prior confirmed suppression to \<50 copies/mL OR confirmed \>1 log10 copies/mL increase in HIV-1 RNA at any time above nadir level where nadir was \>= 50 copies/mL. The phenotypic resistance to a drug is defined as a fold change (i.e, ratio of the IC50 of the clinical isolate to the IC50 of the reference strain) greater than the cut-off for reduced susceptibility. Maximum change from Baseline in Temsavir IC50 fold change based on all on-treatment values has been presented. Baseline is defined as the last non-missing value on or before the date of first dose of study treatment and those values are absolute values. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants available at the specified time points were analyzed.

Time frame: Baseline and up to Week 96

Population: ITT-E Resistance Tested through Week 96 Population

Blood was collected and CD4+ and CD8+ proportion assessment was done by flow cytometery and was carried out at Baseline (Day 1) to evaluate the immunological activity of multiple doses of FTR. Baseline is defined as the last non-missing value on or before the date of first dose of study treatment and the values are absolute values. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed.

Time frame: Baseline and Day 8

Population: ITT-E Monotherapy Population

Blood was collected and CD4+ and CD8+ cell count assessment was done by flow cytometery and was carried out at Baseline (Day 1) to evaluate the immunological activity of multiple doses of FTR. Baseline is defined as the last non-missing value on or before the date of first dose of study treatment and the values are absolute values. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed.

Time frame: Baseline and Day 8

Population: ITT-E Monotherapy Population

Change from monotherapy Baseline in log10 HIV RNA to assess the antiviral activity of temsavir following administration of selected doses of FTR administered orally to HIV-1-infected participants for 7 days. Baseline is defined as the last non-missing value on or before the date of first dose of study treatment. Change from Baseline was calculated as value at indicated time point minus Baseline value. ITT-E Monotherapy Population comprised of participants that were randomized and participated in the monotherapy sub-study and received at least one dose of FTR Monotherapy. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

Time frame: Baseline and up to Day 8 of the monotherapy period

Population: ITT-E Monotherapy Population

Virologic failure is defined clinically as confirmed plasma HIV-1 RNA \>= 50 copies/mL at Week 24 or later or virologic rebound defined as confirmed HIV-1 RNA \>=50 copies/mL at any time after prior confirmed suppression to \<50 copies/mL OR confirmed \>1 log10 copies/mL increase in HIV-1 RNA at any time above nadir level where nadir was \>= 50 copies/mL . The phenotypic resistance to a drug is defined as a fold change (i.e, ratio of the IC50 of the clinical isolate to the IC50 of the reference strain) greater than the cut-off for reduced susceptibility. Maximum change from Baseline in Temsavir IC50 fold change based on all on-treatment values has been presented. Baseline is defined as the last non-missing value on or before the date of first dose of study treatment and those values are absolute values. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants available at the specified time points were analyzed.

Time frame: Baseline and up to Week 24

Population: ITT-E Resistance Tested through Week 24 Population

Maximum decrease from monotherapy Baseline in log10 plasma HIV-1 RNA during monotherapy to assess the antiviral activity of temsavir following administration of selected doses of FTR administered orally to HIV-1-infected participants for 7 days. Baseline is defined as the last non-missing value on or before the date of first dose of study treatment. Change from Baseline was calculated as value at indicated time point minus Baseline value. The data for monotherapy nadir has been presented where nadir represents the maximum decrease from Baseline.

Time frame: Baseline and up to Day 8 of the monotherapy period

Population: ITT-E Monotherapy Population

Participants who administered antiretroviral (ARV) with virologic failure (VF) were assessed. Genotypic substitution included assessment of Reverse Transcriptase (RT) substitution, Protease Inhibitor (PI) substitution and Integrase RAL substitution as per International Acquired Immune Deficiency Syndrome (AIDS) Society-USA (IAS-USA) list. ITT-E Resistance Tested through Week 24 population included participants who met the criteria for Resistance testing, and the confirmatory value or value at discontinuation occurred at or before the end of the Week 24 Snapshot analysis window. The criteria for resistance tested was participant who had virologic failure or met the following criteria a) Participants who achieved viral suppression (plasma HIV-1 RNA \< 50 c/mL) and have confirmed plasma HIV-1 RNA \>= 400 c/mL at any time during the study. b) Participants who were discontinued before achieving viral suppression (plasma HIV-1 RNA \< 50 c/mL) after Week 8 with last plasma HIV-1 RNA \>=400 c/mL.

Time frame: Up to Week 24

Population: ITT-E Resistance Tested through Week 24 Population

Participants who administered ARV with VF were assessed. Genotypic substitution included assessment of RT substitution, PI substitution and Integrase RAL substitution as per IAS-USA list. ITT-E Resistance Tested through Week 48 population included participants who met the criteria for Resistance testing, and the confirmatory value or value at discontinuation occurred at or before the end of the Week 48 Snapshot analysis window. The criteria for resistance tested was participant who had virologic failure or the following criteria a) Participants who achieved viral suppression (plasma HIV-1 RNA \< 50 c/mL) and have confirmed plasma HIV-1 RNA \>= 400 c/mL at any time during the study. b) Participants who were discontinued before achieving viral suppression (plasma HIV-1 RNA \< 50 c/mL) after Week 8 with last plasma HIV-1 RNA \>=400 c/mL.

Time frame: Up to Week 48

Population: ITT-E Resistance Tested through Week 48 Population

Participants who administered ARV with VF were assessed. Genotypic substitution included assessment of RT substitution, PI substitution and Integrase RAL substitution as per IAS-USA list. ITT-E Resistance Tested through Week 96 population included participants who met the criteria for Resistance testing, and the confirmatory value or value at discontinuation occurred at or before the end of the Week 96 Snapshot analysis window. The criteria for resistance tested was participants with virologic failure or the following criteria a) Participants who achieved viral suppression (plasma HIV-1 RNA \< 50 c/mL) and have confirmed plasma HIV-1 RNA \>= 400 c/mL at any time during the study. b) Participants who were discontinued before achieving viral suppression (plasma HIV-1 RNA \< 50 c/mL) after Week 8 with last plasma HIV-1 RNA \>=400 c/mL.

Time frame: Up to Week 96

Population: ITT-E Resistance Tested through Week 96 Population

Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or suspected transmission of an infectious agent via the study drug were categorized as SAE. AEs leading to discontinuation of study therapy were also reported as safety assessment.

Time frame: Up to Day 8 of the monotherapy period

Population: ITT-E Monotherapy Population

Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or suspected transmission of an infectious agent via the study drug were categorized as SAE. AEs leading to discontinuation of study therapy were also reported as safety assessment. Safety Population comprised of participants who received at least one dose of study treatment. Summaries of SAEs and AEs leading to discontinuation or withdrawal through Week X (where X = 48 or 96) included AEs with onset on or after the start of study treatment (i.e. study date of first study treatment intake) up to and including the end of the Week 48 and 96 visit snapshot window.

Time frame: Weeks 48 and 96

Population: Safety Population

Percentage of participants with plasma HIV 1 RNA \< 50 c/mL at Baseline of combination therapy was assessed to evaluate the antiviral activity of four doses of FTR. Baseline of combination therapy was the Day 1 of the combination therapy. Virologic success or failure was determined using the non-missing viral load value at Baseline of combination therapy. The assessment closest to the window target Study Day was used for the analysis. Only those participants with data available at the specified time points were analyzed.

Time frame: Up to Day 8 of the monotherapy period

Population: ITT-E Monotherapy Population

Percentage of participants with plasma HIV 1 RNA \< 50 c/mL at Weeks 48 and 96 using the FDA snapshot algorithm was assessed to evaluate the antiviral activity. Treatment comparisons were not performed as this was an estimation study. Response rates were tabulated by treatment arm with exact Clopper-Pearson binomial 95 percentage CI. Virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment within the snapshot window of the visit of interest.

Time frame: Weeks 48 and 96

Population: ITT-E Population