YEZTUGO is the first-and-only PrEP option that offers twice-yearly, in-office subcutaneous injections1-4
Confirm HIV-negative status prior to injecting YEZTUGO and additionally as clinically appropriate. In addition, counsel individuals about the importance of adherence to scheduled YEZTUGO dosing visits.1
Initiating YEZTUGO1
See additional information on delayed or missed doses
aTablets may be taken with or without food.
bUnless the injection schedule is interrupted.
Dosing recommendations for individuals receiving YEZTUGO and initiating therapy with1:
Maintain scheduled continuation injection dosing
Continue to administer once-every-6-months scheduled continuation dosing of YEZTUGO 927 mg subcutaneously (2 x 1.5-mL injections), plus administer supplemental doses of YEZTUGO as shown in table below.
Schedule for supplemental doses of YEZTUGO
| Time | Dosage |
|---|---|
| On day that strong CYP3A inducer is initiated (should be at least 2 days after YEZTUGO is first initiated) | Supplemental dosage: Step 1 927 mg subcutaneously (2 x 1.5-mL injections) AND 600 mg orally (2 x 300-mg tablets) |
| On day after initiation of strong CYP3A inducer | Supplemental dosage: Step 2 600 mg orally (2 x 300-mg tablets) |
| If strong CYP3A inducer is coadministered for longer than 6 months | Subsequent supplemental dosage: Every 6 monthsd from initiation of strong CYP3A inducer, continue to administer supplemental doses of YEZTUGO as described above in Steps 1 and 2 |
After stopping the strong CYP3A inducer, continue the once-every-6-months scheduled continuation injection dosing of YEZTUGO.
cDosing recommendations are not available for the initiation of YEZTUGO in individuals already receiving strong CYP3A inducers, nor in individuals receiving the weekly oral dosage of YEZTUGO (for more information, see: Anticipated delayed injections below).
d26 weeks ±2 weeks.
Maintain scheduled continuation injection dosing
Continue to administer once-every-6-months scheduled continuation dosing of YEZTUGO 927 mg subcutaneously (2 x 1.5-mL injections), plus administer supplemental doses of YEZTUGO as shown in table below.
Schedule for supplemental doses of YEZTUGO
| Time | Dosage |
|---|---|
| On day that moderate CYP3A inducer is initiated | Supplemental dosage: 463.5 mg subcutaneously (1 x 1.5-mL injection) |
| If moderate CYP3A inducer is coadministered for longer than 6 months | Subsequent supplemental dosage: Every 6 monthsf from initiation of moderate CYP3A inducer, continue to administer a supplemental dose of YEZTUGO as described above |
After stopping the moderate CYP3A inducer, continue the once-every-6-months scheduled continuation injection dosing of YEZTUGO.
eDosing recommendations are not available for the initiation of YEZTUGO in individuals already receiving moderate CYP3A inducers, nor in individuals receiving the weekly oral dosage of YEZTUGO (for more information, see: Anticipated delayed injections below).
f26 weeks ±2 weeks.
What if there is a delayed or missed dose?1-3
Missed oral initiation dose
If an individual misses the Day 2 oral initiation dose (600 mg), have them take it as soon as possible. Instruct them not to take Day 1 and Day 2 oral initiation doses on the same day.
Anticipated delayed injections
During continuation dosing, if the scheduled 6-month injection is anticipated to be delayed by more than 2 weeks, YEZTUGO tablets may be taken.
- One 300-mg oral tablet may be taken once each week (every 7 days) for up to 6 months, until injections resume
- Resume the continuation injection dosing within 1 week (7 days) after the last oral dose
Missed injections
If an individual misses a scheduled injection visit by more than 28 weeks, they should be clinically reassessed to ensure they’re appropriate to resume YEZTUGO and that they remain HIV-1 negative.
- If no YEZTUGO oral tablets have been taken and it has been more than 28 weeks since last injection, restart initiation dosing, then proceed with continuation injections
- Adherence to the injection dosing schedule is strongly recommended
Please see Prescribing Information for additional details.
Multiple ways to acquire YEZTUGO
There are several ways your office may acquire
YEZTUGO for the individuals in your care.
Important resources for your office
Access materials and support to help initiate individuals in your practice on YEZTUGO, along with helpful resources for your staff and practice.
Important Safety Information
BOXED WARNING: RISK OF DRUG RESISTANCE WITH USE OF YEZTUGO IN UNDIAGNOSED HIV-1 INFECTION
- Individuals must be tested for HIV-1 infection prior to initiating YEZTUGO, and with each subsequent injection of YEZTUGO, using a test approved or cleared by the FDA for the diagnosis of acute or primary HIV-1 infection. Drug-resistant HIV-1 variants have been identified with use of YEZTUGO by individuals with undiagnosed HIV-1 infection. Do not initiate YEZTUGO unless negative infection status is confirmed. Individuals who acquire HIV-1 while receiving YEZTUGO must transition to a complete HIV-1 treatment regimen.
Contraindications
- YEZTUGO is contraindicated in individuals with unknown or positive HIV-1 status.
Warnings and precautions
- Comprehensive risk management:
- Use YEZTUGO to reduce the risk of HIV-1 acquisition as part of a comprehensive prevention strategy including adherence to the administration schedule and safer sex practices, including condoms, to reduce the risk of sexually transmitted infections (STIs).
- HIV-1 acquisition risk includes behavioral, biological, or epidemiologic factors including, but not limited to, condomless sex, past or present STIs, self-identified HIV risk, having sexual partners of unknown HIV-1 viremic status, or sexual activity in a high-prevalence area or network. Counsel individuals on the use of other prevention methods to help reduce their risk.
- Use YEZTUGO only in individuals confirmed to be HIV-1 negative. Evaluate for current or recent signs or symptoms consistent with HIV-1 infection. Confirm HIV-1 negative status prior to initiating, prior to each subsequent injection, and as clinically appropriate.
- Potential risk of resistance:
- There is a potential risk of developing resistance to YEZTUGO if an individual acquires HIV-1 before or when receiving YEZTUGO, or following discontinuation. HIV-1 resistance substitutions may emerge in individuals with undiagnosed HIV-1 infection taking only YEZTUGO, because YEZTUGO alone is not a complete regimen for HIV-1 treatment.
- To minimize this risk, it is essential to test before each injection and additionally as clinically appropriate. Individuals confirmed to have HIV-1 must immediately begin a complete HIV-1 treatment regimen.
- Alternative forms of PrEP should be considered after discontinuation of YEZTUGO for those who are at continuing risk of HIV-1 acquisition and should be initiated within 28 weeks of the last YEZTUGO injection.
- Long-acting properties and potential associated risks:
- Residual concentrations of YEZTUGO may remain in systemic circulation for up to 12 months or longer after the last injection.
- Select individuals who agree to the required injection dosing schedule because nonadherence or missed doses could lead to HIV-1 acquisition and development of resistance.
- Serious injection site reactions: Improper administration (intradermal injection) has been associated with serious injection site reactions, including necrosis and ulcer. Only administer YEZTUGO subcutaneously.
Adverse reactions
- Most common adverse reactions (≥5%) in YEZTUGO clinical trials were injection site reactions, headache, and nausea.
Drug interactions
- Strong or moderate CYP3A inducers may significantly decrease YEZTUGO concentrations. Dosage modifications are recommended when initiating these inducers.
- It is not recommended to use YEZTUGO with combined P-gp, UGT1A1, and strong CYP3A inhibitors.
- Coadministration of YEZTUGO with sensitive substrates of CYP3A or P-gp may increase their concentrations and result in the increased risk of their adverse events. YEZTUGO may increase the exposure of drugs primarily metabolized by CYP3A initiated within 9 months after the last injection of YEZTUGO.
Dosage and administration
- HIV screening: Test for HIV-1 infection prior to initiating, prior to each subsequent injection, and as clinically appropriate using an approved or cleared test for the diagnosis of acute or primary HIV-1 infection.
- Dosage: Initiation dosing (injections and tablets) followed by once-every-6-months continuation injection dosing. Tablets may be taken with or without food.
- Initiation: Day 1: 927 mg by subcutaneous injection (2 x 1.5-mL injections) and 600 mg orally (2 x 300-mg tablets). Day 2: 600 mg orally.
- Continuation: 927 mg by subcutaneous injection every 6 months (26 weeks) from date of last injection ±2 weeks.
- Anticipated delayed injections: If scheduled 6-month injection is anticipated to be delayed by more than 2 weeks, YEZTUGO tablets may be taken on an interim basis (for up to 6 months) until injections resume. Dosage is 300 mg orally (1 x 300-mg tablet) once every 7 days. Resume continuation injections within 7 days of the last oral dose.
- Missed injections: If more than 28 weeks have elapsed since the last injection and YEZTUGO tablets have not been taken, restart with initiation dosing if clinically appropriate.
- Dosage modifications of YEZTUGO are recommended when initiating with strong or moderate CYP3A inducers. Consult the full Prescribing Information for recommendations.
Indication
YEZTUGO is indicated for pre‑exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 in adults and adolescents (≥35 kg) who are at risk for HIV-1 acquisition. Individuals must have a negative HIV-1 test prior to initiating YEZTUGO.
Please see full Prescribing Information for YEZTUGO, including BOXED WARNING.
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.
- 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.
- Full efficacy and safety results for Gilead investigational twice-yearly lenacapavir for HIV prevention presented at AIDS 2024. News release. Gilead Sciences, Inc.; July 24, 2024. Accessed January 6, 2025. https://www.gilead.com/news/news-details/2024/full-efficacy-and-safety-results-for-gilead-investigational-twice-yearly-lenacapavir-for-hiv-prevention-presented-at-aids-2024
- Wang H, Guan J, Zhang X, et al. Effect of cold application on the pain and bruising in patients with subcutaneous injection of low-molecular-weight heparin: a meta-analysis. Clin Appl Thromb Hemost. 2020;26:1076029620905349.
- Rava J, Rosenau KA, Wilkie K, Bernacki J, Curcio E, Kuo A. The needle anxiety program: a patient-centered initiative for individuals with developmental disabilities. Cureus. 2023;16(7):e42253.
- Sivri Bilgen B, Balci S. The effect on pain of Buzzy® and ShotBlocker® during the administration of intramuscular injections to children: a randomized controlled trial. J Korean Acad Nurs. 2019;49(4):486-494.