Pre-exposure prophylaxis, or PrEP, is used to prevent you from getting HIV when you do not have it but are at high risk of getting it. Activities that put you at high risk for getting HIV include things like having unprotected sex or injection drug use. There are several different PrEP options available, including tablets and injections. Yeztugo (lenacapavir) uses both. It is a PrEP option to reduce your risk of getting HIV through sex as long as you weigh at least 77 pounds (35 kilograms). Yeztugo is only approved for use by itself to prevent HIV infections, not to treat it. But in order to use it, you will need to have a negative HIV test before you start and before each set of injections.
How Does Yeztugo Work to Prevent HIV?
HIV is a virus that has a coating around it, which is called a capsid. In order for HIV to make copies of itself and spread within your body, it needs to get inside some of your cells. Then the capsid dissolves and the virus uses things within your cells to make new copies of itself. Each copy of the HIV virus has to have its own capsid. Yeztugo is a type of medicine called a capsid inhibitor. It does three things. First, it causes problems with capsid dissolving. If the capsid does not dissolve well, the virus has trouble making copies of itself. Next it causes problems when the HIV virus copies are being made, specifically the parts to make the new capsid. This means there are fewer pieces to make the new capsids for the copies of the virus. Finally, it changes how quickly the new capsids are put together so they are often put together incorrectly. If they are not put together correctly, they are less likely to work.
How Do I Take Yeztugo?
It is very important for you to take Yeztugo at the dose and on the schedule your health care provider recommends. Taking the wrong dose, skipping doses, or not getting doses on time can lower your protection against an HIV infection.
When you first start Yeztugo, as long as you are not taking any medicines that interact with Yeztugo, you will take tablets and get injections. Your health care provider will give you two injections on the same day. You will take two tablets the day you get your injections and two tablets the next day. From that point forward, as long as you stay on schedule, you will get two injections from your health care provider six months (24 to 26 weeks) from your last set of injections. As long as you keep getting your injections every 24 to 26 weeks, you should not need to take any more Yeztugo tablets.
It is also very important for you to plan ahead and be proactive about your doses. This will increase the chances that Yeztugo will work for you. Contact your health care provider if you need to delay your Yeztugo injections longer than 26 weeks from your last set of injections. It may be possible for you to take Yeztugo tablets until you are able to get in for your next injection.
If it has been longer than 28 weeks since your last injection and you did not take additional tablets after it had been 26 weeks since your last set of Yeztugo injections, you may need to restart Yeztugo with two days of tablets and two injections.
What Are Some Other Unique Considerations to Be Aware Of?
In order to maximize the benefits of Yeztugo and minimize your risk of an HIV infection, you should also use safe sex practices. Limit your number of sexual partners. Having sex with multiple partners can increase your odds of getting an HIV infection. Avoid using drugs or alcohol before or during sex. Drugs and alcohol can cloud your judgment and reduce the chance that you will use safe sex practices. Use latex or polyurethane condoms consistently and correctly. Condoms not only reduce your risk of HIV, but they also reduce your risk of other sexually transmitted infections (STIs), including syphilis, chlamydia, and gonorrhea. Yeztugo does not protect you against any of these STIs. It only protects against HIV. Get tested for these infections. Having an STI can increase your risk for giving or getting HIV. Know your sexual partner’s HIV status. Does your partner have HIV? If they have HIV, do they regularly take all of their HIV medicines? Is their viral load undetectable? Someone with HIV with an undetectable viral load cannot transmit HIV, a concept known as U=U (undetectable = untransmittable). The only way to have an undetectable viral load is to take your HIV medicines as prescribed.
In addition to getting tested for HIV before every dose of Yeztugo, you should also get tested if you think you may have HIV or have recently been exposed to it. Early symptoms of HIV can be just like having the flu. Tell your health care provider and follow their recommendations for testing if you have any flu-like symptoms including the following.
- Feeling tired, with aching joints and muscles
- Sore throat
- Rash
- Fever or night sweats
- Headache
- Vomiting or diarrhea
How Was It Studied for the Prevention of HIV?
Two clinical studies were done to see if Yeztugo was safe and effective for preventing HIV infections.
Study one included all females between the ages of 16 and 26 years old who were primarily from Africa and Uganda. People in the study used one of the following PrEP options:
- Yeztugo tablets and injections
- Emtricitabine/tenofovir alafenamide (F/TAF)
- Emtricitabine/tenofovir disoproxil fumarate (F/TDF)
Everyone in the study also took tablets or injections with no medicine in them to match the other groups so no one knew which medicine they were getting.
Study two included males, transgender women, transgender men, gender nonbinary people, and other genders between the ages of 17 and 74 years old from several countries including Argentina, Brazil, Mexico, Peru, South Africa, Thailand, and the United States. People in that study either took Yeztugo tablets and injections or emtricitabine/tenofovir disoproxil fumarate (F/TDF). Tablets and injections without medicine in them were also used in this study to keep everyone from knowing which medicine they were getting. Most of the people in the studies had not ever used any type of PrEP before. It was also common for people in the studies to have sexually transmitted infections. For example, between 11% and 12% of people in study two tested positive for chlamydia at enrollment. This percentage was even higher in study one, with between 24% and 26% testing positive for chlamydia.
What Were the Benefits?
Fewer HIV Infections. Both of these studies looked at the number of people with HIV infections at 52 weeks. People who used Yeztugo were much less likely to get infected with HIV during the study compared to emtricitabine/tenofovir disoproxil fumarate (F/TDF). You can review the number of people who became infected with HIV during these studies in the table below.
HIV Infections
Study 1 | Study 2 | ||||||||
Medicine (number of people) | Yeztugo (2,138) | F/TAF group (2,137)* | F/TDF group (1,070) | Yeztugo (2,138) | F/TDF group (1,088) | ||||
HIV infections | 0 | 39 | 16 | 2 | 9 | ||||
HIV infections per 100 person-years | 0 | 2.02 | 1.69 | 0.1 | 0.93 | ||||
*Note that emtricitabine/tenofovir alafenamide (F/TAF) had not been studied in females before, so it was not known if it would work to prevent HIV.
Better Adherence. These studies also looked at adherence. Taking medicine as prescribed and on time is known as adherence. It is very important to take PrEP as prescribed and on time for it to prevent an HIV infection. People who used Yeztugo were much more likely to get their doses as prescribed and on time. In both studies, at least 91% of the injections were given on time at 26 weeks. At least 92% of the injections were given on time at 52 weeks. Adherence in the other groups was not as high.
Adherence to the tablets was divided into three levels: high, medium, and low. High adherence was defined as taking at least four of the seven weekly doses. Medium adherence was defined as taking two or three of the seven weekly doses. Low adherence was defined as taking less than two doses of the weekly seven. You can review the adherence rates in the table below.
Estimated Adherence
Study 1 | Study 2 | |||
F/TAF group | F/TDF group | F/TDF group | ||
26 weeks | High | 22% | 4% | 67% |
Medium | 8% | 7% | 7% | |
Low | 70% | 89% | 26% | |
52 weeks | High | 11% | 0% | 62% |
Medium | 5% | 7% | 11% | |
Low | 84% | 93% | 27% | |
In summary, people in these studies were more likely to take their medicine as prescribed and less likely to get an HIV infection using Yeztugo as PrEP than if they take no medicine or took emtricitabine/tenofovir disoproxil fumarate (F/TDF). Your results may differ from what was seen in these studies.
What Should I Know About Possible Drug Interactions?
Yeztugo stays in your body for a long time. This is why after taking tablets for two days and getting your first injections, you only have to get injections every six months. This also means Yeztugo can interact with other medicines for a long time, even up to nine months after your last dose.
Certain medicines can lower your blood levels of Yeztugo. If you take any of these medicines, you may need to get extra doses of Yeztugo tablets, injections, or both for it to work to prevent an HIV infection. A few examples of some of the medicines that interact with Yeztugo include the following.
- Carbamazepine (Carbatrol, Tegretol, and others), which is a medicine commonly used to treat seizures or nerve pain
- Phenytoin (Dilantin, Phenytek, and others), phenobarbital, or primidone, which is a medicine to treat seizures
- Rifampin (Rifadin), which is a medicine commonly used to treat an infection called tuberculosis
- St. John’s wort, which is a supplement that may be used for depression
Before you start Yeztugo, tell your health care provider about all of your medicines. While you are using Yeztugo, tell your health care provider if you are supposed to start or stop taking any other medicines. By doing these things, your health care provider can make sure that you get the right dose of Yeztugo.
Is There a Cost Savings Program?
There is a coupon available from the drugmaker that may allow you to pay $0 for your prescription. Whether you are eligible depends on whether you have prescription insurance and what type of insurance you have. You can find out more at www.yeztugo.com/coverage-cost-support.
