Fostemsavir

A SAE is defined as any untoward medical occurrence that, at any dose, results in results in death, is life- threatening, requires inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant, abnormal pregnancy outcomes or a suspected transmission of any infectious agent via an authorized medicinal product.

An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AESI is defined as an AE of a scientific and medical concern specific to the study intervention, which may require further investigation in order to characterize and understand it.

Plasma samples were collected for analysis of HIV-1 RNA. Mean change in log10 HIV-1 RNA from Day 1 was estimated using analysis of covariance (ANCOVA) with log10 HIV-1 RNA change from Day 1 at Day 8 as dependent variable, treatment (fostemsavir or placebo) as an independent variable, and Day 1 log10 HIV-1 RNA as a continuous covariate. Change from Day 1 was calculated as value at Day 8 minus value at Day 1. The analysis was performed on Intent-to-Treat Exposed (ITT-E) Population which comprised of all randomized participants who received at least one dose of study treatment. Missing HIV-1 RNA values at Day 8 were imputed using (a) Day 1 Observation Carried Forward (D1OCF) for participants without a value during blinded treatment (i.e, imputing a zero change from Day 1) or (b) Last Observation Carried Forward (LOCF) for participants with an early value during blinded treatment before the Day 8 analysis visit window.

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.

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.

The primary assessment of the antiviral activity of BMS-663068 was assessed on the log10 change from Baseline in HIV RNA to Day 9. Baseline was the last non-missing observation before first dose (Day 1 pre-dose) and change from Baseline was calculated by subtracting Baseline value from post-Baseline visit value. An analysis of covariance (ANCOVA) model correcting for Baseline HIV viral load and treatment group was used to test the differences in mean log10 decrease in HIV RNA at Day 9 between 2 regimen groups by antiretroviral treatment history (ARV \[antiretroviral\] naive, ARV experienced, and combined \[ARV naive + ARV experienced\]). For the combined group (ARV naive +ARV experienced) an additional ANCOVA was used correcting also for treatment history as an additional covariate. Only Clade B participants were included in the population.

To assess the effect of varying degrees of renal impairment on the exposure of BMS-626529 after a single oral-dose administration of the pro-drug, BMS-663068, will be evaluated by assessing the primary endpoints of Cmax, for BMS-626529.

Pharmacokinetic parameter includes: maximal observed concentration (Cmax) for EE and NE.

Pharmacokinetic parameter includes: area under the concentration-time curve in one dosing interval (AUC(TAU)) for EE and NE.

PK parameters for BMS-626529 in the absence or presence of multiple doses of maraviroc include: \- Cmax

PK parameters for BMS-626529 in the absence or presence of multiple doses of maraviroc include: \- AUC(TAU)

PK parameters for maraviroc in the absence or presence of BMS-663068 include: \- Cmax

PK parameters for maraviroc in the absence or presence of BMS-663068 include: \- AUC(TAU)

In the presence or absence of multiple doses of DRV/COBI or COBI