Study to Evaluate Safety, Pharmacokinetics, and Antiviral Activity of Lenacapavir Administered Subcutaneously in Human Immunodeficiency Virus (HIV) -1 Infected Adults

Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)

An AE was any untoward medical occurrence in a clinical study participant administered a medicinal product, which does not necessarily have a causal relationship with the treatment. An AE could therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs were defined as any AE with an onset date on or after the study drug start date.

Time frame: Day 1 through 225 days

Part A and Part B: Percentage of Participants Experiencing Treatment Emergent Laboratory Abnormalities

Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each participant.

Time frame: Day 1 through 225 days

Part A and Part B Pharmacokinetic (PK) Parameter: AUCinf of Lenacapavir, TAF and Its Metabolite TFV

AUCinf is defined as area under the concentration versus time curve from time zero to infinity.

Time frame: Part A: 0 (predose),1,2,4,8,12,24 h postdose on Day 1, anytime on Days 3,4,7,8,9,10,14,29,43,57,85,113,141,169,197,225; Part B: 0 (predose),0.5,1,2,3,4,6,8,10,12,24 and 48 h postdose on Day 1, approximately Day 1 predose time on Days 4,5,6,7,8,9,10

Part A and Part B PK Parameter: AUClast of Lenacapavir, TAF and Its Metabolite TFV

AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration.

Time frame: Part A: 0 (predose),1,2,4,8,12,24 h postdose on Day 1, anytime on Days 3,4,7,8,9,10,14,29,43,57,85,113,141,169,197,225; Part B: 0 (predose),0.5,1,2,3,4,6,8,10,12,24 and 48 h postdose on Day 1, approximately Day 1 predose time on Days 4,5,6,7,8,9,10

Part A and Part B PK Parameter: Cmax of Lenacapavir, TAF and Its Metabolite TFV

Cmax is defined as the maximum observed concentration of drug.

Time frame: Part A: 0 (predose),1,2,4,8,12,24 h postdose on Day 1, anytime on Days 3,4,7,8,9,10,14,29,43,57,85,113,141,169,197,225; Part B: 0 (predose),0.5,1,2,3,4,6,8,10,12,24 and 48 h postdose on Day 1, approximately Day 1 predose time on Days 4,5,6,7,8,9,10

Part B PK Parameter: AUCinf of TFV-DP Metabolite of TAF

AUCinf is defined as area under the concentration versus time curve from time zero to infinity.

Time frame: Part B: 0 (predose), 1, 2, 4, 6, 8, 12, 24 and 48 hours post dose on Day 1, approximately Day 1 predose time on Days 4, 5 (if possible), 6 (if possible), 7, 8, 9, 10

Part B PK Parameter: AUClast of TFV-DP Metabolite of TAF

AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration.

Time frame: Part B: 0 (predose), 1, 2, 4, 6, 8, 12, 24 and 48 hours post dose on Day 1, approximately Day 1 predose time on Days 4, 5 (if possible), 6 (if possible), 7, 8, 9, 10

Part B PK Parameter: Cmax of TFV-DP Metabolite of TAF

Cmax is defined as the maximum observed concentration of drug.

Time frame: Part B: 0 (predose), 1, 2, 4, 6, 8, 12, 24 and 48 hours post dose on Day 1, approximately Day 1 predose time on Days 4, 5 (if possible), 6 (if possible), 7, 8, 9, 10

Part A: Percentage of Participants Ever Achieving HIV-1 RNA < 50 Copies/mL by Day 10

Time frame: Day 10

Part A: Number of Participants Experiencing Any Emergence of Capsid Inhibitor Resistance

Time frame: Day 10

Part A: Number of Participants Experiencing Any Emergence of Capsid Inhibitor Resistance

Post-Monotherapy Resistance Analysis Population analyzed for this outcome measure included any participant who received at least 1 dose of study drug/placebo, maintained their study drug regimen, \& met one of following virologic failure criteria: * HIV-1 RNA ≥ 50 copies/mL \& \< 1 log10 HIV-1 RNA reduction from Day 10 at Day 57 visit, confirmed at a scheduled or unscheduled visit at least 2 weeks following Day 57 * At any visit following Day 10, after achieving HIV-1 RNA \< 50 copies/mL, a rebound in HIV-1 RNA to ≥ 50 copies/mL, which was subsequently confirmed at following scheduled or unscheduled visit; OR At any visit, a \> 1 log10 increase in HIV-1 RNA from nadir, which was subsequently confirmed at following scheduled or unscheduled visit; * Any participant with HIV-1 RNA ≥ 50 copies/mL at study endpoint or study discontinuation who didn't meet any of criteria above also had protease (PR)/reverse transcriptase (RT), integrase (IN), \&capsid (CA) genotyping \& phenotyping performed.

Time frame: Day 10 through Day 225

Part B: Number of Participants Experiencing Any Emergence of TAF Resistance

Time frame: Day 10

Part B: Number of Participants Experiencing Any Emergence of TAF Resistance

TAF Resistance testing was performed for any participant meeting Post-Monotherapy Resistance Analysis Population criteria - it included any participant who received at least 1 dose of study drug/placebo, maintained their study drug regimen, \& met one of the following virologic failure criteria: * HIV-1 RNA ≥50 copies/mL \& \< 1 log10 HIV-1 RNA reduction from D10 at the D57 visit, confirmed at scheduled or unscheduled visit at least 2 weeks following D57 * At any visit following D10, after achieving HIV-1 RNA\< 50 copies/mL, a rebound in HIV-1 RNA to ≥50 copies/mL, which was subsequently confirmed at the following scheduled/unscheduled visit; OR At any visit, a \> 1 log10 increase in HIV-1 RNA from nadir, which was subsequently confirmed at the following scheduled or unscheduled visit; * Any participant with HIV-1 RNA ≥50 copies/mL at study endpoint or study discontinuation who didn't meet any of the criteria above also had PR/RT, IN, and CA genotyping \& phenotyping performed. D = Day

Time frame: Day 10 through Day 225