A Closer Look at the Drug Depot. For US healthcare providers only.

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.

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.

Please see additional Important Safety Information later in this video, and accompanying full Prescribing Information for YEZTUGO, including BOXED WARNING, available at YeztugoPI.com.

Hi, I'm Christopher Roberson, a nurse practitioner and an infectious disease specialist.

Hi, I'm Ashton Chase, a nurse practitioner and HIV specialist.

I would say I have around 50 patients on YEZTUGO, and probably 15 of them have received their second dose.

I have about 40 patients on YEZTUGO, including women and men of diverse backgrounds.

I talk about PrEP all the time, and with every STI test I order, I have a PrEP discussion. I'll ask, "Are you doing anything for your sexual health?” and “How are you protecting yourself from HIV?" Even if they're just here as a walk-in, I'll ask if they've had a recent HIV test. If not, let's get it, and then let's talk about PrEP as well. Sex and PrEP are a lot of what I talk about every day.

Just having sex makes a person a candidate to learn about PrEP, so I talk about PrEP with every single patient. I ask them about their thoughts on HIV prevention. Also, I wanna know what do they know about PrEP. That opens the conversation and allows me to dispel any myths that they may have assumed about PrEP​.

We don't do a great job in our community of talking about sex. It's taboo, right? But we're all human. Sex is a natural thing, and I feel like STI visits are the time to say, "Do you know anything about PrEP?"

A lot of our patients don't know anything about PrEP, so I just meet them where they're at, and then I start that education by planting that seed, because HIV can be transmitted through sexual exposure—and there is no cure. But it can be preventable with the right strategies.

This consideration of applying ice for injections is not specific to YEZTUGO.

When patients are showing up for an acute visit or to be screened for STIs, you should be having a discussion about strategies to reduce the likelihood of this occurring again. This may include a conversation about PrEP options including YEZTUGO as part of a comprehensive prevention approach. I tell them this could have been that time that you were diagnosed with HIV in addition to gonorrhea, chlamydia, or syphilis. We don't want that to occur, so let's take steps to help prevent it.

​I believe YEZTUGO allows my patients to say, "If I'm gonna have sex, I know I'm protected against HIV with the injections I get every six months." The trial showed YEZTUGO is effective at preventing HIV through sex. When you couple that with the twice-yearly dosing schedule, it offers a long-acting option with potentially fewer appointments.

Granted, I tell them, PrEP is only one part of their overall sexual health, and they should make sure to use barrier protection, too.

For me, having different dosing options, including a twice-yearly option, in my PrEP toolkit is useful. I can help patients choose an option that fits into their lives. Having the variety of options has the potential impact of preventing new HIV infections.

As sexual beings, women can also get HIV through sex. So when it comes to my female patients, the PURPOSE 1 study set the stage with this landmark phase 3 trial, which was pivotal in the PrEP world. It was studied in Black women and adolescents, and it allowed women to remain in the study if they became pregnant or started breastfeeding.

And that is just beautiful to me because women, especially women of color, have been historically underrepresented. We want to talk about mammograms and cervical cancer screenings and colonoscopies. Let's put PrEP conversations on the map, too, as part of routine preventive healthcare.

When my patients show up for PrEP, I congratulate them, especially the women in my care, because PrEP is not just for men who have sex with men. HIV is a human virus that can be transmitted through sex regardless of gender. I appreciate having an additional HIV prevention option like YEZTUGO to consider with my patients.

Ultimately, it can be for a variety of people, providing they are HIV negative. Someone who is sexually active and looking for HIV protection every six months is a potential candidate. I consider individuals on a holistic level, including their lifestyle, to help me determine whether it's a right fit for them.

So PrEP is for almost everyone. Things like the HIV prevalence where a person lives could be a reason to consider PrEP, along with other additional factors. Where I live, the HIV prevalence is high, so if someone is sexually active and HIV negative, they might be a good candidate for YEZTUGO. I have patients on PrEP who are well into their seventies, patients who are postmenopausal, and just because a person or someone is older or postmenopausal does not mean they're not sexually active or that they could not benefit from PrEP.

I said yes to being the provider that is willing to help this community and to supporting patients in making informed decisions about their health.

I said yes to knowing the data from the clinical trials and because my patients deserve to know about their HIV prevention options.

I said yes to HIV prevention and to empowering my patients with the option of six months of HIV protection at a time.

Important Safety Information (continued)

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.

Please see full Prescribing Information for YEZTUGO, including BOXED WARNING, available at YeztugoPI.com.

For more information about YEZTUGO, visit YEZTUGOhcp.com.

Setting Patient Expectations & YEZTUGO For US healthcare providers only.

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.

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.

Please see additional Important Safety Information later in this video, and accompanying full Prescribing Information for YEZTUGO, including BOXED WARNING, available at YeztugoPI.com.

Hi, my name is Ashton Chase. I'm a nurse practitioner and HIV specialist. I have about 40 patients on YEZTUGO, and I was the second provider who administered YEZTUGO, when it first came out in June of 2025.

Hi, I'm Christopher Roberson, a nurse practitioner and also an infectious disease specialist. I would say I have around 50 patients on YEZTUGO, and probably 15 of them have received their second dose. I've been researching HIV prevention and prescribing PrEP for over a decade.​

Setting expectations around YEZTUGO and the injection process is very important. And we do this by letting the patients know that there may be some pain, informing them of the potential adverse reactions and reminding them to contact me if they experience any side effects. I find that this could help create a positive experience.

When I start, I always tell my patients how proud I am of them for taking the initiative and making this choice. I let them know that this is their health, and this is a really empowering decision.

I usually tell my patients YEZTUGO is injected in the subcutaneous tissue of the abdomen or the thigh twice a year. It creates a drug depot under the skin that allows the medication to be slowly released over time, and that's how you're going to be protected for six months.

I just try and break it down and share the experiences of my other patients.

When I explain how YEZTUGO works, I don't use terms like “drug depot.”

I tell patients that it forms like a small pocket under the skin that slowly releases the medication over time. It stays there gradually getting smaller as the medication does its job. That really helps set expectations.

​I always tell my patients about potential side effects that the two most reported injection site reactions in the clinical trials were nodules, also called bumps, and pain at the injection site.

But I find it important to tell them that not everyone will have the same experience with the YEZTUGO injections.

Other potential ISRs could be induration, swelling, itching, erythema, bruising, and warmth, but these were less common. Some may feel a bump at the injection site, which may or may not be seen.

I also let my patients know that the bump and other injection site reactions became less common with later injections of YEZTUGO in the clinical trials.

I'll come in with two ice packs and I'm like, "All right, we're going to give you two injections today." Then I ask where they prefer to receive their injections, in their abdomen or their thigh, and depending on where they say, I'll put the ice packs on them.

And then after the injection, I encourage them to reapply the ice packs.

I let them know that different types of injections may cause different levels of pain, but to help address that pain response we're going to put an ice pack on your abdomen or your thighs.

I find patients are unsure what to expect before they receive their first injection. I remind them to take a deep breath, and I walk them through the initiation process.

I'm like, "Okay, your HIV test was negative, so today you'll receive two injections and take two tablets while you're here in office. Then tomorrow, take the remaining two tablets at home. Put the pill bottle next to your toothbrush so you remember to take them first thing in the morning."

After both initiation injections are done, I'll have them sit up and take their first set of tablets. And then I'm documenting and checking for any potential adverse reactions and reminding them to take their tablets the next day. By the time I'm done with that, it's probably been about 15 minutes, so I'll let them know I placed their HIV lab orders to be completed before their next injection appointment.

And then we're done with day one of initiation.

I remind them that I will see them in six months for follow-up injections, but if they need anything before then, please let me know.

I go get the tablets and a bottle of water, and I watch them take their first dose of tablets right there in my office. And then the day after, I'm usually calling them to make sure they took their second dose of tablets.

Although the cushion is two weeks before and two weeks after their target six-month injection date, I encourage my office staff to schedule that patient on the first day of their four-week window period. I try to be proactive in that way, and now we have a whole four weeks to adjust continuing dosing appointments if necessary.

I appreciate that as well because they could have changed their insurance, and we may need a new prior authorization. It gives us time to potentially work out any kinks and also to schedule around life and vacations.

​I try to make the experience really positive, especially the first injection appointment. When patients come back for their second appointment, they're on the table, they have their shirt up, and they're ready to go. And I'm like, "Okay, all the encouragement worked."

I actually thank my patients when they show up. I give them credit for taking this part of their sexual health seriously. That positivity and support really sticks with the patients.

Important Safety Information (continued)

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.

Please see full Prescribing Information for YEZTUGO, including BOXED WARNING, available at YeztugoPI.com.

For more information about YEZTUGO, visit YEZTUGOhcp.com.

Getting Started with YEZTUGO For US healthcare providers only.

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.

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.

Please see additional Important Safety Information later in this video, and accompanying full Prescribing Information for YEZTUGO, including BOXED WARNING, available at YeztugoPI.com.

Hi, I'm Omar. I'm a family nurse practitioner. Before you can prescribe YEZTUGO, you need to ensure you have the right setup in your practice.

It's really helpful to have it set up in your EHR. I try to make it simple for my practice by setting up workflows and processes that my colleagues can use. I set up a profile for the YEZTUGO initiation and continuation prescriptions. I had a nurse educator from Gilead come to my office and give my staff some training on giving the YEZTUGO injections and answer any questions we had on administration.

At first, I had to educate myself. I had a lot of questions about accessing YEZTUGO, so I reached out to Gilead Field Reimbursement Manager. They provided me information on navigating coverage for my patients who wanted YEZTUGO.

Before starting your patients on YEZTUGO, you have to make sure both the injections and the tablets are covered. It's important to reach out to the specialty pharmacy as they can help with prior authorizations and ensure that any coverage breaks are being met with coupons or other programs. Something else that really helped me was building a connection directly with my pharmacy manager.

This way, we can better understand our patient's coverage.

You also have to confirm that your patient is HIV negative. It helps to keep the most recent test results readily available to avoid any delays. One thing I like to do is to keep standing HIV labs in my patients' charts. That way, they can test as often as they want. But I also tell them they need to do an HIV test prior to their injection appointment so we can confirm their negative status. I think another part of preparing patients for YEZTUGO starts with giving them the entire picture, like the context about what they're getting and what to expect. I found that by laying out this process with more context, it really made a difference. Patients walked out of my office feeling like they have a clear understanding of what to expect with YEZTUGO.

It's important to remember that for initiation, two prescriptions are required, one for the oral tablets and one for the injections. After that, for the continuation dose, you only need one prescription for the injections. There was an illustrative example of what the two prescriptions may look like provided by Gilead that could be helpful.

When I send the prescription for the initiation dose, I also send the refill for the continuation dose and then send a message to the pharmacy to ensure they have seen the refill and prevent any disruptions.

I have a deck with everything I need, so when I have a patient coming in, I put the ICD-10 code, I type in the due date, and copy and paste my information, and we're set for the next appointment.

When it comes to scheduling the appointment for injections with my patient, it is also important to think six months ahead.

Knowing what my patient has planned in six months or where they might be, like on vacation, is helpful in scheduling the appointment.

If my patient can't make it to their appointment, there are options available for when they're ready to continue their YEZTUGO injections again.

My patients receive a text message from my office two weeks before letting them know that they have an upcoming appointment, and then another one approximately one day before their next upcoming appointment.

That's a system that we follow to help support adherence and encourage our patients to come back for their next injections.

I said yes because of the impact I know I can make in my community. I think that as providers, we have a responsibility to our community and to the patients we see.

About three years ago, I didn't know much about PrEP. It wasn't something we were doing in my practice, so I referred patients out.

When I saw something about YEZTUGO online, I started to read about it, and I reached out to a rep, and I was like, "I'm interested in this." That opened the door for me. Now I have PrEP conversations every day with my patients, and now my clinic has close to 100 patients on YEZTUGO.

Important Safety Information (continued)

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.

Please see full Prescribing Information for YEZTUGO, including BOXED WARNING, available at YeztugoPI.com.

For more information about YEZTUGO, visit YEZTUGOhcp.com.

Addressing Potential Injection Site Reactions. For US healthcare providers only.

When administering subcutaneous injections of YEZTUGO, you may want to know more about potential injection site reactions (or ISRs).

This video offers more details about ISRs from two clinical trials, as well as strategies to help address one of these potential ISRs, specifically injection site pain.

Before we begin, let’s review the indication and some Important Safety Information about YEZTUGO.

Indication

YEZTUGO is indicated for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 in adults and adolescents (≥35 kg) kilograms who are at risk for HIV-1 acquisition. Individuals must have a negative HIV-1 test prior to initiating YEZTUGO.

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.

Please see additional Important Safety Information later in this video and accompanying full Prescribing Information for YEZTUGO, including Boxed Warning, available at YeztugoPI.com.

Let’s start by talking about how often ISRs were reported in two phase 3 clinical trials: PURPOSE 1 and PURPOSE 2.

ISRs reported in greater than or equal to 2% of participants receiving YEZTUGO in either study were nodule, pain, induration, swelling, pruritus, erythema, bruising, and warmth. To learn more about these clinical trials, go to YEZTUGOhcp.com.

While ISRs were common and reported across both trials among people on YEZTUGO, the majority of ISRs were mild to moderate. No serious ISRs occurred in either PURPOSE 1 or PURPOSE 2.

In each trial, discontinuations due to ISRs were low.

So, now that you know what ISRs to watch for, let’s review some tips to keep in mind while injecting YEZTUGO.

Finding an appropriate injection site may take some careful consideration to help fully insert the needle into the subcutaneous layer where the drug depot forms.

Every person has a different body type. Pick a site that allows you to pinch enough skin to inject subcutaneously.

One of the most important steps you can take is to learn and practice the proper injection technique.

Improper administration of lenacapavir (in other words, by intradermal injection instead of subcutaneous injection) has been associated with serious ISRs. Remember, YEZTUGO should only be administered subcutaneously.

To review the steps in the injection process in more detail, see the “Key Steps to Inject” episode of this video series and see the full Prescribing Information and Instructions for Use for more details on how to prepare and administer YEZTUGO.

After someone receives their injections, remind them to report any ISRs they may experience at any time. If they have questions or concerns about ISRs or other adverse reactions, remind them to contact you.

One specific ISR you may be interested in helping to address is potential injection site pain. There may be some other techniques you’ve used in the past to address this pain during subcutaneous injections. Although these techniques are not specific to YEZTUGO, consider if they may be appropriate for some people receiving YEZTUGO injections.

For example, you may be used to rotating injection sites between visits. Injection sites include the abdomen (at least 2 inches from the navel), or thigh. Remember that the second injection site must be at least 4 inches from the first site.

Applying an ice pack to each site prior to injection may be another strategy you have used in the past. Consider keeping a few ice packs in your office and ready for your injection visits.

In addition to the techniques used in your experience with subcutaneous injections, there may be other methods for you to consider when addressing injection site pain.

One method could include counseling or coaching someone through the injection process to comfort or distract them from the potential pain during injection.

Pain mitigations for other injectables have also included using topical numbing creams before, or oral analgesics after the injection (if clinically appropriate).

If clinically indicated, you may also consider skin stimulation devices that are designed to decrease pain perception through local skin stimulation by applying both cold and vibration to the site. Remember that these strategies are not specific to YEZTUGO. Follow the pain management protocol for your institution.

After someone receives their YEZTUGO injections, remind them to tell you if they have any ISRs or other side effects.

You can also report any suspected adverse reactions to Gilead Sciences, Inc. at 1-800-GILEAD-5, or to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Let’s review some of what you learned today. Remember to carefully select an injection site that allows for proper injection. Before the next injection visit, refresh your memory and practice the proper injection technique. You may also consider other strategies (such as ice packs) that may help address injection site pain as clinically appropriate.

Important Safety Information (continued)

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.

Please see full Prescribing Information for YEZTUGO, including BOXED WARNING, available at YeztugoPI.com.

For more information about YEZTUGO, visit YEZTUGOhcp.com.

Following the Dosing Schedule. For US healthcare providers only.

Consistency is important for YEZTUGO, which is why it’s important for both you and someone in your care to understand the dosing schedule and how to follow it.

In this video, you’ll learn more about the YEZTUGO dosing schedule and get tips on helping someone track each of their scheduled visits.

Before we begin, let’s review the indication and some Important Safety Information about YEZTUGO.

Indication

YEZTUGO is indicated for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 in adults and adolescents (≥35 kg) kilograms who are at risk for HIV-1 acquisition. Individuals must have a negative HIV-1 test prior to initiating YEZTUGO.

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.

Please see additional Important Safety Information later in this video and accompanying full Prescribing Information for YEZTUGO, including Boxed Warning, available at YeztugoPI.com.

Let’s start with a basic understanding of the typical schedule. As a twice-yearly injectable PrEP, YEZTUGO is administered every 6 months (or 26 weeks) by a healthcare provider in a clinical setting.

When someone starts YEZTUGO, the first 2 days are slightly different than the continuation dosing that follows.

That’s because on Day 1, during an in-office visit, two subcutaneous injections will be administered and a loading dose of two 300-mg oral tablets will be given.

On Day 2, at home, two more 300-mg oral tablets are taken. If an individual misses the Day 2 oral loading dose (600 mg), have them take it as soon as possible. They should not take the Day 1 and Day 2 oral loading doses on the same day.

After that, continuation dosing is administered every 6 months with 2 injections (with no oral tablets) when the dosing schedule is followed as prescribed. Ideally, continuation injections would be administered on the date that you schedule. However, a lot can change about someone’s plans in the 6 months between visits.

That’s why the dosing schedule is designed for flexibility in continuation dosing. When needed, YEZTUGO can be administered up to 2 weeks earlier or 2 weeks later than the scheduled injection date, 6 months from the last injection. It may be helpful to check in with each person before their next visit, to see if this flexibility would help them stay on schedule.

Remember that you must confirm a negative HIV-1 test prior to each injection of YEZTUGO, and additionally as clinically appropriate.

Now that you know more about the dosing schedule, how do you help someone follow that schedule for their 6-month injections?

It may help to give them some basic context about how YEZTUGO can only prevent HIV if it’s administered as prescribed.

It’s important to follow the dosing schedule as closely as possible to avoid interrupting their HIV prevention. To help them stay on schedule, consider staying in touch with them between visits.

Let’s look ahead a few months, just before their scheduled 6-month injection visit. If they do miss injections for whatever reason, there are steps you can take.

Make sure they notify you as soon as possible if their next appointment may need to change.

Let’s talk about that situation, where they anticipate a delay in their scheduled 6-month injection visit by more than 2 weeks. When that happens and it’s been 26 to 28 weeks since their last injection, YEZTUGO oral tablets may be used on an interim basis.

They would take one 300-mg oral tablet every 7 days for up to 6 months, until injections resume. They must resume the continuation injection dosing within 7 days after the last oral dose.

If someone accidentally misses a scheduled injection visit by more than 28 weeks and YEZTUGO tablets have not been taken, they should be clinically reassessed to ensure they’re appropriate to resume YEZTUGO and that they remain HIV-1 negative.

If they are HIV-1 negative and appropriate to resume, that person needs to restart the initiation dosing schedule with oral tablets and injections. After the initiation dosing, they will continue with continuation injection dosing. See the Prescribing Information for more details.

Remind them that they will need to be tested to confirm negative HIV-1 status prior to each YEZTUGO injection, and as clinically appropriate. What are some other ways that you can help someone follow their schedule?

You may want to recommend that they use several types of reminders to keep track of upcoming visits for HIV-1 testing and injections.

This includes writing dates on a calendar, using apps on their phone, or other methods they typically use to remember when to take other medications.

You may also consider sending them reminders, notifications, or calls to help remind them of their scheduled visits.

Tell them to contact you right away if they are unable to attend their scheduled appointments, and to discuss appropriate next steps.

Now that you have more details about the dosing schedule, let’s discuss a couple of situations where dosing modifications may be needed.

Supplemental doses of YEZTUGO are recommended for individuals initiating therapy with either strong or moderate CYP3A inducers.

Continue to administer once-every-6-months scheduled continuation dosing of YEZTUGO 927 mg subcutaneously (two 1.5-milliliter injections), plus administer supplemental doses of YEZTUGO as shown in the following tables. Strong CYP3A inducers may be initiated starting at least 2 days after YEZTUGO is first initiated, while moderate CYP3A inducers may be started any time after YEZTUGO is first initiated. See full Prescribing Information for more details.

Let’s review some of what you learned today. Remember to test to confirm negative HIV-1 status prior to injecting YEZTUGO and additionally thereafter as clinically appropriate. After the initiation dosing, YEZTUGO is administered by subcutaneous injection every 6 months. Continuation dosing is flexible and options are available if the scheduled injection is missed (or anticipated to be delayed). Also, reminders are an important way to help someone remember their scheduled visits. As needed, follow instructions for dosing modifications per the full Prescribing Information.

Important Safety Information (continued)

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.

Please see full Prescribing Information for YEZTUGO, including BOXED WARNING, available at YeztugoPI.com.

For more information about YEZTUGO, visit YEZTUGOhcp.com.