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.
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 |