Safety evaluated in 2 large clinical studies1
Adverse reactions (all grades) reported in ≥2%a of participants receiving YEZTUGO in both PURPOSE 1 or PURPOSE 21
No serious ISRs occurred in either PURPOSE 1 or PURPOSE 2
| Adverse reaction | PURPOSE 1 | PURPOSE 2 | ||
|---|---|---|---|---|
| YEZTUGO N=2140 |
FTC/TDFb N=1070 |
YEZTUGO N=2183 |
FTC/TDFb N=1088 |
|
| ISRs | 69% | 34% | 83% | 69% |
| Nodule | 64% | 17%c | 63% | 39% |
| Pain | 31% | 24%c | 56% | 53% |
| Induration | 4% | <1%c | 16% | 10% |
| Swelling | 4% | 5%c | 7% | 10% |
| Pruritus | 2% | 1%c | 3% | 3% |
| Erythema | 1% | 1%c | 17% | 19% |
| Bruising | <1% | <1%c | 3% | 4% |
| Warmth | <1% | <1%c | 2% | 2% |
| Headache | 7% | 8% | 2% | 2% |
| Nausea | 5% | 11% | 2% | 4% |
| Dizziness | 4% | 6% | <1% | 1% |
| Vomiting | 4% | 7% | <1% | 1% |
| Diarrhea | 4% | 4% | 2% | 2% |
| PURPOSE 1 | ||
|---|---|---|
| Adverse reaction |
YEZTUGO N=2140 | FTC/TDFb N=1070 |
| ISRs | 69% | 34% |
| Nodule | 64% | 17%c |
| Pain | 31% | 24%c |
| Induration | 4% | <1%c |
| Swelling | 4% | 5%c |
| Pruritus | 2% | 1%c |
| Erythema | 1% | 1%c |
| Bruising | <1% | <1%c |
| Warmth | <1% | <1%c |
| Headache | 7% | 8% |
| Nausea | 5% | 11% |
| Dizziness | 4% | 6% |
| Vomiting | 4% | 7% |
| Diarrhea | 4% | 4% |
| PURPOSE 2 | ||
|---|---|---|
| Adverse reaction |
YEZTUGO N=2183 | FTC/TDFb N=1088 |
| ISRs | 83% | 69% |
| Nodule | 63% | 39% |
| Pain | 56% | 53% |
| Induration | 16% | 10% |
| Swelling | 7% | 10% |
| Pruritus | 3% | 3% |
| Erythema | 17% | 19% |
| Bruising | 3% | 4% |
| Warmth | 2% | 2% |
| Headache | 2% | 2% |
| Nausea | 2% | 4% |
| Dizziness | <1% | 1% |
| Vomiting | <1% | 1% |
| Diarrhea | 2% | 2% |
aFrequencies of ARs are based on all AEs attributed to study drug (or to the procedure for injection site reactions) by the investigator.
bParticipants received placebo subcutaneous injections (polyethylene glycol 400).
cIncludes participants who received either FTC/TDF or FTC/TAF (N=3205).
Majority of ISRs were mild or moderate and incidence rates decreased with subsequent injections1
Adapted with permission from Bekker et al. N Engl J Med. 2024.
Adapted with permission from Kelley et al. N Engl J Med. 2025.
dInjection site nodule, pain, and swelling were the most commonly reported ISRs. Of these, Grade 3 ISRs reported in the YEZTUGO group: nodule (n=1; <0.1%); FTC/TDF group: pain (n=1; <0.1%).
eParticipants receiving placebo injections were either receiving FTC/TAF or FTC/TDF.
fInjection site nodule, pain, and erythema were the most commonly reported ISRs. Of these, Grade 3 ISRs reported in the YEZTUGO group: pain (n=4; 0.2%) and erythema (n=3; 0.1%); FTC/TDF group: pain (n=1; <0.1%).
gParticipants receiving placebo injections received FTC/TDF.
Actor portrayals.
Drug interactions
Please see the full Prescribing Information for more details on drug interactions with YEZTUGO.
Strong or moderate inducers of CYP3A may significantly decrease plasma concentrations of lenacapavir, which may reduce the effectiveness of YEZTUGO. Dosage modifications are recommended when initiating these inducers. See dosage modifications.
Combined P-gp, UGT1A1, and strong CYP3A inhibitors may significantly increase plasma concentrations of YEZTUGO. Concomitant administration with YEZTUGO is not recommended.
YEZTUGO is a moderate inhibitor of CYP3A and a P-gp inhibitor that may increase the concentrations of coadministered sensitive substrates of CYP3A and P-gp, and increase risk of their adverse events. See the prescribing information of these sensitive substrates for dosing recommendations or appropriate monitoring of safety. YEZTUGO may increase the exposure of drugs primarily metabolized by CYP3A initiated within 9 months after the last subcutaneous dose of YEZTUGO.
HIV prevention done in your office
YEZTUGO is a twice-yearly subcutaneous injectable administered in your office.1
Multiple ways to acquire YEZTUGO
There are several ways your office may acquire YEZTUGO for the individuals in your care.
AEs=adverse events; ARs=adverse reactions; Bsl=baseline; ISR=injection site reaction; FTC/TAF=emtricitabine/tenofovir alafenamide fumarate; FTC/TDF=emtricitabine/tenofovir disoproxil fumarate; P-gp=permeability glycoprotein; Wk=week.
References:
- YEZTUGO. Prescribing information. Gilead Sciences, Inc.; 2025.
- Bekker LG, Das M, Abdool Karim Q, et al; PURPOSE 1 study team. Twice-yearly lenacapavir or daily F/TAF for HIV prevention in cisgender women. N Engl J Med. 2024;391(13):1179-1192.
- Bekker LG, Das M, Abdool Karim Q, et al; PURPOSE 1 study team. Twice-yearly lenacapavir or daily F/TAF for HIV prevention in cisgender women. Supplementary Appendix. N Engl J Med. 2024;391(13):S1-S68.
- Kelley CF, Acevedo-Quiñones M, Agwu AL, et al; PURPOSE 2 study team. Twice-yearly lenacapavir for HIV prevention in men and gender-diverse persons. N Engl J Med. 2025;392(13):1261-1276.
- Kelley CF, Acevedo-Quiñones M, Agwu AL, et al; PURPOSE 2 study team. Twice-yearly lenacapavir for HIV prevention in men and gender-diverse persons. Supplementary Appendix. N Engl J Med. 2025;392(13):S1-S70.