Trial Outcomes & Findings for Oral Islatravir (MK-8591) Once-Monthly as Preexposure Prophylaxis (PrEP) in Men and Transgender Women Who Are at High Risk for HIV-1 Infection (MK-8591-024) (NCT NCT04652700)

Last Updated: 2025-01-13

Results Overview

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experienced an AE will be reported for each treatment arm.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

494 participants

Primary outcome timeframe

Up to approximately 10.5 months

Results posted on

2025-01-13

Participant Flow

Participants were randomized at 23 study sites in France, Japan, Peru, South Africa, and the United States.

Participant milestones

Participant milestones
Measure	Part 1: ISL & Parts 2 & 3: FTC/TDF or FTC/TAF Participants received 60 mg tablet of ISL once monthly (QM) plus placebo to FTC/TDF tablet once daily (QD) or placebo to FTC/TAF tablet QD in Part 1. Participants then received open-label FTC/TDF or FTC/TAF in Parts 2 and 3.	Parts 1 to 3: FTC/TDF or FTC/TAF Participants received 200/245 mg or 200/300 mg of FTC/TDF combination tablet QD or 200/25 mg of FTC/TAF combination tablet QD at investigator's discretion plus placebo to ISL tablet QM in Part 1. Participants continued to receive open-label FTC/TDF or FTC/TAF in Parts 2 and 3.
Part 1: Blinded Study Medication STARTED	328	166
Part 1: Blinded Study Medication COMPLETED	0	0
Part 1: Blinded Study Medication NOT COMPLETED	328	166
Parts 2 and 3: Open-Label FTC TDF or TAF STARTED	306	154
Parts 2 and 3: Open-Label FTC TDF or TAF COMPLETED	0	0
Parts 2 and 3: Open-Label FTC TDF or TAF NOT COMPLETED	306	154

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1: ISL & Parts 2 & 3: FTC/TDF or FTC/TAF Participants received 60 mg tablet of ISL once monthly (QM) plus placebo to FTC/TDF tablet once daily (QD) or placebo to FTC/TAF tablet QD in Part 1. Participants then received open-label FTC/TDF or FTC/TAF in Parts 2 and 3.	Parts 1 to 3: FTC/TDF or FTC/TAF Participants received 200/245 mg or 200/300 mg of FTC/TDF combination tablet QD or 200/25 mg of FTC/TAF combination tablet QD at investigator's discretion plus placebo to ISL tablet QM in Part 1. Participants continued to receive open-label FTC/TDF or FTC/TAF in Parts 2 and 3.
Part 1: Blinded Study Medication Adverse Event	1	0
Part 1: Blinded Study Medication Lost to Follow-up	7	2
Part 1: Blinded Study Medication Multiple reasons (primarily discontinuation of blinded treatment)	308	160
Part 1: Blinded Study Medication Withdrawal by Subject	12	4
Parts 2 and 3: Open-Label FTC TDF or TAF Lost to Follow-up	34	9
Parts 2 and 3: Open-Label FTC TDF or TAF Not reported	6	1
Parts 2 and 3: Open-Label FTC TDF or TAF Physician Decision	0	2
Parts 2 and 3: Open-Label FTC TDF or TAF Study terminated by Sponsor	227	119
Parts 2 and 3: Open-Label FTC TDF or TAF Withdrawal by Subject	39	23

Baseline Characteristics

Oral Islatravir (MK-8591) Once-Monthly as Preexposure Prophylaxis (PrEP) in Men and Transgender Women Who Are at High Risk for HIV-1 Infection (MK-8591-024)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1: ISL & Parts 2 & 3: FTC/TDF or FTC/TAF n=328 Participants Participants received 60 mg tablet of ISL QM plus placebo to FTC/TDF tablet QD or placebo to FTC/TAF tablet QD in Part 1. Participants then received open-label FTC/TDF or FTC/TAF in Parts 2 and 3.	Parts 1 to 3: FTC/TDF or FTC/TAF n=166 Participants Participants received 200/245 mg or 200/300 mg of FTC/TDF combination tablet QD or 200/25 mg of FTC/TAF combination tablet QD at investigator's discretion plus placebo to ISL tablet QM in Part 1. Participants continued to receive open-label FTC/TDF or FTC/TAF in Parts 2 and 3.	Total n=494 Participants Total of all reporting groups
Age, Continuous	29.6 years STANDARD_DEVIATION 9.6 • n=5 Participants	29.5 years STANDARD_DEVIATION 9.2 • n=7 Participants	29.6 years STANDARD_DEVIATION 9.5 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	328 Participants n=5 Participants	166 Participants n=7 Participants	494 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	111 Participants n=5 Participants	51 Participants n=7 Participants	162 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	214 Participants n=5 Participants	111 Participants n=7 Participants	325 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	70 Participants n=5 Participants	31 Participants n=7 Participants	101 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	83 Participants n=5 Participants	41 Participants n=7 Participants	124 Participants n=5 Participants
Race (NIH/OMB) White	135 Participants n=5 Participants	71 Participants n=7 Participants	206 Participants n=5 Participants
Race (NIH/OMB) More than one race	35 Participants n=5 Participants	20 Participants n=7 Participants	55 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to approximately 10.5 months

Population: All treated participants are included.

Outcome measures

Outcome measures
Measure	Part 1: ISL & Parts 2 & 3: FTC/TDF or FTC/TAF n=328 Participants Participants received 60 mg tablet of ISL QM plus placebo to FTC/TDF tablet QD or placebo to FTC/TAF tablet QD in Part 1. Participants then received open-label FTC/TDF or FTC/TAF in Parts 2 and 3.	Parts 1 to 3: FTC/TDF or FTC/TAF n=166 Participants Participants received 200/245 mg or 200/300 mg of FTC/TDF combination tablet QD or 200/25 mg of FTC/TAF combination tablet QD at investigator's discretion plus placebo to ISL tablet QM in Part 1. Participants continued to receive open-label FTC/TDF or FTC/TAF in Parts 2 and 3.
Number of Participants Who Experienced an Adverse Event (AE) During Blinded Treatment	211 Participants	128 Participants

PRIMARY outcome

Timeframe: Up to approximately 9 months

Population: All treated participants are included.

Outcome measures

Outcome measures
Measure	Part 1: ISL & Parts 2 & 3: FTC/TDF or FTC/TAF n=328 Participants Participants received 60 mg tablet of ISL QM plus placebo to FTC/TDF tablet QD or placebo to FTC/TAF tablet QD in Part 1. Participants then received open-label FTC/TDF or FTC/TAF in Parts 2 and 3.	Parts 1 to 3: FTC/TDF or FTC/TAF n=166 Participants Participants received 200/245 mg or 200/300 mg of FTC/TDF combination tablet QD or 200/25 mg of FTC/TAF combination tablet QD at investigator's discretion plus placebo to ISL tablet QM in Part 1. Participants continued to receive open-label FTC/TDF or FTC/TAF in Parts 2 and 3.
Number of Participants Who Discontinued From Blinded Study Treatment Due to an AE	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to approximately 10.5 months

Population: All participants who were randomized and received ≥1 dose of study intervention are included (participants with confirmed HIV infections prior to or at randomization are excluded).

The number of participants with confirmed HIV-1 infections during the blinded treatment period is presented.

Outcome measures

Outcome measures
Measure	Part 1: ISL & Parts 2 & 3: FTC/TDF or FTC/TAF n=328 Participants Participants received 60 mg tablet of ISL QM plus placebo to FTC/TDF tablet QD or placebo to FTC/TAF tablet QD in Part 1. Participants then received open-label FTC/TDF or FTC/TAF in Parts 2 and 3.	Parts 1 to 3: FTC/TDF or FTC/TAF n=166 Participants Participants received 200/245 mg or 200/300 mg of FTC/TDF combination tablet QD or 200/25 mg of FTC/TAF combination tablet QD at investigator's discretion plus placebo to ISL tablet QM in Part 1. Participants continued to receive open-label FTC/TDF or FTC/TAF in Parts 2 and 3.
Number of Participants With Confirmed HIV-1 Infection	0 Participants	0 Participants

Adverse Events

Part 1: ISL

Serious events: 6 serious events

Other events: 120 other events

Deaths: 0 deaths

Parts 2 & 3: Open-label PrEP (ISL in Part 1)

Serious events: 18 serious events

Other events: 230 other events

Deaths: 0 deaths

Part 1: FTC/TDF or FTC/TAF

Serious events: 1 serious events

Other events: 88 other events

Deaths: 0 deaths

Parts 2 & 3: Open-label PrEP (FTC/TDF or FTC/TAF in Part 1)

Serious events: 5 serious events

Other events: 104 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Trials Disclosure

Merck Sharp & Dohme LLC

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Part 1: ISL n=328 participants at risk Participants received blinded 60 mg tablet of ISL QM plus placebo to FTC/TDF tablet QD or placebo to FTC/TAF tablet QD in Part 1.	Parts 2 & 3: Open-label PrEP (ISL in Part 1) n=306 participants at risk Participants received open-label FTC/TDF or FTC/TAF (based on regional availability) QD in Parts 2 and 3 (after blinded ISL in Part 1).	Part 1: FTC/TDF or FTC/TAF n=166 participants at risk Participants received blinded FTC/TDF (200/245 mg or 200/300 mg) or FTC/TAF (200/25 mg) QD in Part 1.	Parts 2 & 3: Open-label PrEP (FTC/TDF or FTC/TAF in Part 1) n=154 participants at risk Participants received open-label FTC/TDF or FTC/TAF (based on regional availability) QD in Parts 2 and 3 (after blinded FTC/TDF or FTC/TAF in Part 1).
Gastrointestinal disorders Proctitis	0.30% 1/328 • Number of events 1 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/306 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/166 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/154 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Infections and infestations Appendicitis	0.30% 1/328 • Number of events 1 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/306 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/166 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	1.3% 2/154 • Number of events 2 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Infections and infestations COVID-19	0.30% 1/328 • Number of events 1 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	2.6% 8/306 • Number of events 8 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.60% 1/166 • Number of events 1 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.65% 1/154 • Number of events 1 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Infections and infestations Cellulitis	0.00% 0/328 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.33% 1/306 • Number of events 1 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/166 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/154 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Infections and infestations Dengue fever	0.00% 0/328 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.33% 1/306 • Number of events 1 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/166 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/154 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Infections and infestations Folliculitis	0.30% 1/328 • Number of events 1 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/306 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/166 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/154 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Infections and infestations Peritonsillar abscess	0.00% 0/328 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.33% 1/306 • Number of events 1 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/166 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/154 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Infections and infestations Pneumonia	0.30% 1/328 • Number of events 1 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/306 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/166 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/154 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Infections and infestations Pyelonephritis acute	0.00% 0/328 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.33% 1/306 • Number of events 1 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/166 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/154 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Infections and infestations Upper respiratory tract infection	0.00% 0/328 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/306 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/166 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.65% 1/154 • Number of events 1 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Infections and infestations Viral infection	0.00% 0/328 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.33% 1/306 • Number of events 1 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/166 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/154 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Injury, poisoning and procedural complications Alcohol poisoning	0.00% 0/328 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.33% 1/306 • Number of events 1 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/166 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/154 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Injury, poisoning and procedural complications Jaw fracture	0.00% 0/328 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.33% 1/306 • Number of events 1 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/166 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/154 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Injury, poisoning and procedural complications Ulna fracture	0.00% 0/328 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.33% 1/306 • Number of events 1 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/166 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/154 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Metabolism and nutrition disorders Hyperglycaemia	0.30% 1/328 • Number of events 1 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.33% 1/306 • Number of events 1 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/166 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/154 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Nervous system disorders Amnesia	0.00% 0/328 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.33% 1/306 • Number of events 1 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/166 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/154 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Nervous system disorders Epilepsy	0.30% 1/328 • Number of events 1 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.33% 1/306 • Number of events 1 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/166 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/154 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Psychiatric disorders Acute psychosis	0.00% 0/328 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.33% 1/306 • Number of events 1 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/166 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/154 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Psychiatric disorders Substance-induced psychotic disorder	0.00% 0/328 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.33% 1/306 • Number of events 1 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/166 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/154 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Psychiatric disorders Suicidal ideation	0.00% 0/328 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/306 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/166 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.65% 1/154 • Number of events 1 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).

Other adverse events
Measure	Part 1: ISL n=328 participants at risk Participants received blinded 60 mg tablet of ISL QM plus placebo to FTC/TDF tablet QD or placebo to FTC/TAF tablet QD in Part 1.	Parts 2 & 3: Open-label PrEP (ISL in Part 1) n=306 participants at risk Participants received open-label FTC/TDF or FTC/TAF (based on regional availability) QD in Parts 2 and 3 (after blinded ISL in Part 1).	Part 1: FTC/TDF or FTC/TAF n=166 participants at risk Participants received blinded FTC/TDF (200/245 mg or 200/300 mg) or FTC/TAF (200/25 mg) QD in Part 1.	Parts 2 & 3: Open-label PrEP (FTC/TDF or FTC/TAF in Part 1) n=154 participants at risk Participants received open-label FTC/TDF or FTC/TAF (based on regional availability) QD in Parts 2 and 3 (after blinded FTC/TDF or FTC/TAF in Part 1).
Gastrointestinal disorders Diarrhoea	5.8% 19/328 • Number of events 21 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	4.6% 14/306 • Number of events 14 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	5.4% 9/166 • Number of events 11 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	7.1% 11/154 • Number of events 11 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Gastrointestinal disorders Haemorrhoids	0.91% 3/328 • Number of events 3 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	3.9% 12/306 • Number of events 12 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	1.2% 2/166 • Number of events 2 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	5.2% 8/154 • Number of events 9 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Infections and infestations COVID-19	10.7% 35/328 • Number of events 36 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	22.5% 69/306 • Number of events 79 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	12.7% 21/166 • Number of events 21 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	24.0% 37/154 • Number of events 41 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Infections and infestations Chlamydial infection	0.00% 0/328 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	5.6% 17/306 • Number of events 19 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	1.2% 2/166 • Number of events 2 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	4.5% 7/154 • Number of events 9 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Infections and infestations Influenza	1.2% 4/328 • Number of events 4 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	4.6% 14/306 • Number of events 19 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	3.6% 6/166 • Number of events 7 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	9.1% 14/154 • Number of events 15 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Infections and infestations Latent syphilis	0.61% 2/328 • Number of events 2 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	5.9% 18/306 • Number of events 22 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.00% 0/166 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	1.9% 3/154 • Number of events 3 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Infections and infestations Nasopharyngitis	4.3% 14/328 • Number of events 14 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	8.8% 27/306 • Number of events 33 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	4.2% 7/166 • Number of events 8 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	7.1% 11/154 • Number of events 12 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Infections and infestations Oropharyngeal gonococcal infection	4.9% 16/328 • Number of events 18 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	13.4% 41/306 • Number of events 55 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	6.6% 11/166 • Number of events 11 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	15.6% 24/154 • Number of events 29 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Infections and infestations Pharyngeal chlamydia infection	0.61% 2/328 • Number of events 2 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	5.9% 18/306 • Number of events 18 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	0.60% 1/166 • Number of events 1 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	1.3% 2/154 • Number of events 2 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Infections and infestations Proctitis chlamydial	6.1% 20/328 • Number of events 25 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	21.2% 65/306 • Number of events 81 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	8.4% 14/166 • Number of events 14 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	17.5% 27/154 • Number of events 37 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Infections and infestations Proctitis gonococcal	4.0% 13/328 • Number of events 14 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	16.7% 51/306 • Number of events 63 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	9.0% 15/166 • Number of events 16 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	19.5% 30/154 • Number of events 41 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Infections and infestations Syphilis	3.0% 10/328 • Number of events 10 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	6.2% 19/306 • Number of events 20 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	4.2% 7/166 • Number of events 7 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	9.7% 15/154 • Number of events 15 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Infections and infestations Upper respiratory tract infection	3.0% 10/328 • Number of events 10 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	10.1% 31/306 • Number of events 32 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	4.8% 8/166 • Number of events 8 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	11.0% 17/154 • Number of events 20 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Investigations CD4 lymphocytes decreased	0.30% 1/328 • Number of events 1 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	7.8% 24/306 • Number of events 29 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	1.8% 3/166 • Number of events 3 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	3.9% 6/154 • Number of events 10 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Nervous system disorders Headache	4.3% 14/328 • Number of events 14 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	5.9% 18/306 • Number of events 23 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	6.0% 10/166 • Number of events 10 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	5.8% 9/154 • Number of events 11 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Respiratory, thoracic and mediastinal disorders Cough	1.5% 5/328 • Number of events 5 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	5.2% 16/306 • Number of events 17 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	1.8% 3/166 • Number of events 3 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	3.2% 5/154 • Number of events 5 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	1.8% 6/328 • Number of events 6 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	4.2% 13/306 • Number of events 15 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	4.2% 7/166 • Number of events 8 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).	5.8% 9/154 • Number of events 10 • Entire Study: Blinded Treatment (Part 1) + Open-Label Standard-of-Care Treatment (Parts 2 & 3) [Up to approximately 26 months] All treated participants are included. Data are presented separately for Part 1 (randomized blinded treatment) and Parts 2 \& 3 (open-label standard-of-care preexposure prophylaxis \[PrEP\] periods). Open-label PrEP treatment was pooled per protocol as standard-of-care treatment (FTC/TAF as available only for US sites, FTC/TDF as brand \[200/300 mg\] or generic \[200/245 mg\]).