A New Twice-Yearly PrEP: What Is Yeztugo?

There are many different ways people can protect themselves against HIV. First, there was a daily pill. Then, an injectable that is taken every two months became available. Now, a new option with a longer time between dosing is out: In June, Gilead Sciences announced it had received approval for Yeztugo® (lenacapavir) from the U.S. Food and Drug Administration.

Yeztugo is an injectable pre-exposure prophylaxis (PrEP) against HIV, taken twice a year in a clinic setting. PrEP medications prevent HIV infections in various ways.

Yeztugo falls into the class of capsid inhibitors, which work by targeting the protein shell that protects the virus’s genetic material and enzymes.

“I’m excited that we’re getting more options,” said Antonio Urbina, MD, Medical Director for the Institute for Advanced Medicine at Mount Sinai. “There are many different people out there with different circumstances, and the more options we have out there to protect people from HIV, the better.”

What is Yeztugo, and who might it be suitable for? In a Q&A, Dr. Urbina explains the drug in detail and how it stacks up against other PrEP options.

Antonio Urbina, MD, Medical Director, Institute for Advanced Medicine at Mount Sinai

How effective is Yeztugo at protecting against HIV?

Two large phase 3 clinical trials were used as evidence for Yeztugo to be approved: PURPOSE 1 and PURPOSE 2. The two trials examined more than 8,000 participants collectively.

What stood out to me was that these studies not only examined the drug in cisgender men who have sex with men, but also transgender men and women, nonbinary people, and adolescent girls. They were very inclusive studies.

The data were extraordinary: in PURPOSE 1, there were zero HIV infections in the Yeztugo group, whereas the daily oral PrEP group had 16 cases. In PURPOSE 2, there were two HIV infections in the Yeztugo group, while the daily oral PrEP group had 16 acquisitions.

Statistical analysis not only showed Yeztugo was significantly superior at preventing HIV compared to the background rate, but also to the daily PrEP group.

How is Yeztugo given?

On the first visit, the patient is given two injections, and two pill versions of the same drug to take in the clinic. Then, the patient is given two of the same pills to take home to take on the second day.

It is very important for patients to take the second-day pills, because doing so will ensure peak plasma concentration that same day. That means patients will have achieved optimal protection against HIV in as quickly as two days, which is impressive. If the patient fails to take the pills, that protection can be delayed by as much as 10 days.

After that, the patient only needs to come in every six months for injections, with a flexibility window of two weeks before and after the date.

What are its side effects?

The most common side effects occurred at the injection site. There were the usual pain, swelling, and itchiness reactions, and most were mild to moderate. However, there is an injection site reaction that occurred in a large proportion of patients—roughly 65 percent—which was described as the formation of a “nodule.”

To understand these nodules, we have to go into how this drug works. Yeztugo is injected into the subcutaneous layer, under the skin but above the muscle. A deposit of the drug sits there and dissipates over time. For many patients, the nodules might not be visible, although if you touch the site, you might feel a slight lump there.

For some patients, the nodules might be slightly visible and appear raised. Thus, patients are offered a choice on injection sites, and Yeztugo can be given in the abdomen area or the thigh. It is important to educate patients on what to expect.

And for some, the nodules never develop at all. It does not mean, however, that the drug is not working. It varies by patient.

What might be the advantage of Yeztugo over other PrEP options?

One of the biggest challenges of daily oral PrEP is adherence. People are forgetful. When enough daily doses are missed, the protection wanes. Having an option every six months ensures there are no gaps.

The fact that you have to go into clinic for this option—while a hassle—is actually helpful for fighting stigma. Some people don’t like having these medications visible in their cabinets, or having to interact with pharmacists about them.

Lastly—this is less talked about—is the potential to bring more accessible HIV prevention into vulnerable communities and populations. It is harder to bring pills to a community and ask them to take them every day, and refill them every month, compared to giving injections just twice a year. Also, Yeztugo is approved for adolescents, which makes this accessible to younger people as well.

How does one access Yeztugo?

It starts with a conversation with your care provider. There are many different PrEP options out there, and if it is determined a patient would like to go with Yeztugo, an HIV test is done to ensure the patient is negative before starting the regimen.

And then, at subsequent visits, all the label for Yeztugo requires is to document that the patient is HIV negative. Gilead Sciences has not set any sort of protocol for maintenance testing.

However, just because this option is taken twice a year doesn’t mean that the patient should only go for screening that number of times. If a person is very sexually active, it’s a good idea to go for screening not just for HIV, but also other sexually transmitted infections, every three months.

Will Yeztugo be covered by insurance?

The news media has reported that Yeztugo has a list price of roughly $28,000 per year, or about $14,000 per shot. That is a large price tag to swallow, but with commercial insurance, out-of-pocket costs are likely to be lower. Depending on an individual’s insurance, that copay might still be too high, though.

With Yeztugo’s approval being recent, insurance companies are waiting for guidance from state and federal regulatory bodies, including Medicaid. The New York State Department of Health’s AIDS Institute has already given an interim recommendation to clinicians for Yeztugo as a “preferred PrEP regimen,” as long the individual doesn’t mind injections every six months. I’m hopeful that insurance will soon cover Yeztugo on their list of covered drugs.

What has Gilead Sciences said about copay assistance for Yeztugo?

In various statements, the company has said that for people with commercial insurance, through its Copay Saving Program, out-of-pocket costs may be reduced to as low as zero. Some uninsured eligible individuals might also be able to access Yeztugo free of charge through its Advancing Access Patient Assistance Program.

What are the current options for PrEP?

  Truvada Descovy Apretude Yeztugo
Generic drug name Emtricitabine/tenofovir disoproxil fumarate Emtricitabine/tenofovir alafenamide Cabotegravir Lenacapivir
Administration Pill, oral Pill, oral Intramuscular injection, gluteal (buttock) Subcutaneous injection, abdomen or thigh
Dosing Daily Daily Every two months Every six months
Class of drug Nucleoside reverse transcriptase inhibitor Nucleoside reverse transcriptase inhibitor Integrase strand transfer inhibitor Capsid inhibitor
Generic available Yes No No No

Clearing Misconceptions About Gender-Affirming Care for Transgender and Gender-Diverse People

Gender-affirming care for transgender and gender-diverse people has advanced over the past decade, but connecting patients to this care efficiently remains a challenge, hindered by a lack of awareness.

“Patients worry about what they need to know even before being able to speak to a doctor for gender-affirming care,” said Joshua Safer, MD, Executive Director of the Center for Transgender Medicine and Surgery at Mount Sinai.

Even health providers can be unsure of what gender-affirming care entails. Many once believed that they would have to run a series of tests before even being able to refer their transgender patients for specialized care, Dr. Safer said. “It’s a misconception that they have to do anything,” he noted. “There are some tests that they could run that would make their patients’ lives easier, but it is fine to send patients along even without those tests.”

In a conversation with his doctor, Miroslav Djordjevic, MD, Clinical Professor of Urology, patient Kyshane Rowe talks about how life has changed since he began the transition process 10 years ago, and how Mount Sinai’s Center for Transgender Medicine and Surgery helped him along the way. Click here to watch the video.

As part of efforts to raise awareness about transgender care, Dr. Safer weighs in on common misconceptions about gender-affirming care and shares tips for patients and providers on how to make the experience seamless.

For patients

Seeking gender-affirming care can be overwhelming for transgender and gender-diverse patients, Dr. Safer said. With care that can stretch across multiple specialties, including endocrinology, gynecology, urology, and various surgical subspecialties, patients sometimes think they need to do a bunch of research before even speaking with a provider.

However, speaking with your primary care doctor could be part of that care journey, Dr. Safer said: “Providers can help guide patients with what they need to align their bodies with their gender identities.”  

  • It might be helpful for transgender patients to consider their fertility goals when seeking gender-affirming care. That would help outline what medical or surgical options make sense.
  • Letters of support from mental health and primary care providers are required to be eligible for gender-affirming surgery. Obtaining those letters isn’t necessarily complicated, and our Center provides templates for them.
  • Out-of-state patients seeking surgical care in New York City need to be housed within a 90-minute travel distance of the surgery office for at least two weeks. Additionally, the accommodation cannot be a walkup apartment, and a caretaker must be present to assist with cleaning and daily activities.

The Center for Transgender Medicine and Surgery at Mount Sinai has set up a hotline to help patients with appointments, or even direct them to “champion providers” within the Health System—providers trained in gender-affirming care, Dr. Safer said.

For patients, click here to learn more about accessing transgender care

For providers

Gender-affirming care in a primary care setting doesn’t need to be complicated, Dr. Safer said. It is fine to refer transgender patients after initial assessments without needing a bunch of tests.

However, should the provider choose to order baseline testing for patients, it would make the patients’ care experience more convenient. Here are some typical tests a provider can consider:

There is also a misconception that because insurance companies categorize gender-affirming surgery as a treatment for gender dysphoria, patients need to be seen by a mental health provider, Dr. Safer said.

“If there are underlying mental health concerns, do refer those patients for treatment,” he noted. “But there are many transgender patients who have no mental health concerns and are merely seeking gender-affirming care.”

Providers within the Mount Sinai Health System would already be connected within the Epic system for referrals to any needed specialist, expediting the process, Dr. Safer said. For providers outside the Health System, a dedicated hotline team from the Center for Transgender Medicine and Surgery is there to assist, he added.

For providers, click here to learn more about connecting transgender patients to care

In Sickness and In Health: Why LGBT Health Equality Matters

Guest post by Jose Sepulveda

When Apple CEO Tim Cook came out, he said “We pave the sunlit path toward justice together, brick by brick. This is my brick.” Coming out was not going to change his life. It was not going to change my life much either, but somewhere, there was a young teen who was able to see a little more hope. These small bricks, small steps forward, help the unseen. (more…)

Hepatitis C: Promising Treatment Developments

Over the past few years, enormous strides have been made in treatment options for people living with hepatitis C, a form of viral hepatitis that causes chronic liver disease. Treatments in the past were difficult to tolerate, produced numerous side effects, and for a large percentage of patients, were often unsuccessful. Promising new drugs, however, will likely reduce the burden of treatment (the work patients do to care for themselves, such as visiting the doctor or going for medical tests), produce quicker results, and cause fewer and less profound side effects. (more…)

Worried About HIV? New Prevention Methods Offer More Options

The HIV prevention landscape has changed dramatically over the last few years. In the past, most health care professionals could only support consistent use of condoms, frequent testing, and risk-reduction counseling for HIV prevention. Today, these approaches can be used in conjunction with new methods that have been developed and are now available to the public to lower risk of HIV infection. (more…)

Pin It on Pinterest