Monica Gandhi, MD, MPH, is the director of the UCSF-Bay Area Center for AIDS Research (CFAR). She’s also a professor of medicine and associate division chief in the Division of HIV, Infectious Diseases, and Global Medicine at UCSF, San Francisco General Hospital in San Francisco. The information here represents her knowledge and expertise as a medical professional. Gandhi was not involved in the development or clinical trials for lenacapavir (Yeztugo).
Around 1.2 million people in the U.S. live with HIV, a lifelong disease. Without treatment, the virus attacks your immune system and leads to AIDS, acquired immunodeficiency syndrome.
In the U.S., about 31,800 people are newly diagnosed with HIV each year. So the FDA approved lenacapavir (Yeztugo) in June of 2025 — a new pre-exposure prophylactic (PrEP) for HIV.
Monica Gandhi, MD, MPH, director of the UCSF-Bay Area Center for AIDS Research (CFAR), professor of medicine, and associate division chief in the Division of HIV, Infectious Diseases, and Global Health at UCSF, San Francisco General Hospital explains more about how PrEP works, who it’s for, and how lenacapavir can lower your risk for HIV.
What is Pre-Exposure Prophylactic (PrEP)?
Pre-exposure means you take a pill or shot before you’re exposed to HIV. Prophylaxis means the medicine prevents HIV before the infection even starts. So PrEP can stop HIV from taking hold in your body if you're exposed.
PrEP is what we call biomedical prevention. That’s because the medicine does the work to stop the virus, versus wearing a condom, which is a behavioral prevention.
How did researchers discover lenacapavir?
All PrEP medicines were first HIV treatments. In fact, lenacapavir was first approved in 2022 to treat HIV. But when a PrEP agent treats HIV, it’s usually combined with other agents — you don’t just get one medicine as treatment.
Lenacapavir is the fourth FDA-approved PrEP agent. It joins medications like:
- A monthly injectable shot called cabotegravir (Apretude)
- Descovy, a daily oral pill approved for non-vaginal sex
- Truvada, a daily oral pill
Lenacapavir is the second PrEP agent in shot form that's been approved by the FDA.
What type of medication is lenacapavir?
Lenacapavir is the first HIV medication called a capsid inhibitor. It targets the protein shell that protects the virus’s genetic material.
Prior to June of this year, lenacapavir was used against treatment-resistant viruses. But in the meantime, researchers were studying the medicine for prevention, too.
What did the studies show?
The PURPOSE 1 study compared over 2,000 cisgender women in Uganda and South Africa taking lenacapavir to over 2,000 women taking older oral PrEP pills. The study found something remarkable:
- About 55 HIV infections happened when taking daily PrEP pills
- No HIV infections happened when taking the lenacapavir shot
The PURPOSE 2 study looked at 3,265 men and gender-diverse individuals, and only:
- Nine HIV infections happened when taking daily PrEP pills
- Two HIV infections happened in people taking lenacapavir
That means the shot had a 96% efficacy rate — ability to prevent HIV. Those numbers showed that lenacapavir is actually better than the pill.
Guidance on who takes PrEP
The CDC put out some guidance on Sept. 18th, 2025 to help explain who’s at risk for HIV and who PrEP can help.
You should take lenacapavir if you have a higher HIV risk, such as you:
- Had an STD in the last six months
- Have multiple sexual partners
- Are a man who has sex with men who aren't monogamous
- Have ongoing, non-monogamous sexual activity and without STD testing
- Aren’t aware of your partner’s HIV risk factors
You should not take lenacapavir if you:
- Already have HIV
- Already have HIV and are trying to prevent it
That’s important to know because treatment for HIV usually involves more than one medicine. The virus can become clever and evade one medication, becoming resistant.
In fact, your doctor will give you an HIV test to make sure it’s negative before every shot.
How do you take lenacapavir?
Lenacapavir is approved for adolescents and adults who weigh 77 pounds (35 kilograms) or more. You’ll get the shot once every six months, after the medicine reaches the right level inside your body.
So the first time you take it, you’ll get:
- Two pills by mouth along with your first shot
- Then, two pills the next day
This helps the medicine levels get high enough to protect you against HIV much faster.
After that, you’ll take the shot every six months, usually right underneath the skin in your belly (abdomen). You have to go to a clinic to get it — there aren’t studies on giving yourself the shot.
That’s because the shot has more liquid in it — about 3 milliliters of a very oily, bright yellow substance. So the injections can be a little tricky to do on your own. But the shots are still easier to get twice a year compared to a daily pill for some people.
Why is the daily pill harder?
People have a hard time taking prevention pills. It feels like it's easy, but it's not.
- People have complicated lives.
- They don't want other people to see it.
- People forget.
- People go in and out of insurance, or in and out of housing.
- There's addiction, there's depression — it just can be hard to take a pill every day.
Are there side effects to lenacapavir?
Like any medicine, there are potential side effects. With lenacapavir, you may get an injection site reaction. There are two main reactions: pain and nodules.
Pain. If you inject at a 90-degree angle and put ice on it afterward, the pain is usually mild.
Nodule. Lenacapavir nodule reactions seem to happen more often. About two-thirds of people (67%) get little bumps on their skin after the shot.
Keep in mind, you’ll take two separate shots each time. You’ll get one shot on each side of your belly. This can cause many little bumps.
Nodule reactions after lenacapavir
I have been using lenacapavir in my clinical treatment and can attest that those nodules are real. I have patients who ask me to feel them.
The people I see this bother the most are those who have a thin abdomen. Most people have some degree of fat around their stomach and so the nodules are more hidden.
I've also seen that men tend to be more bothered than women. But some people aren't bothered at all. It's very important to tell people ahead of time that this is a very likely side effect.
How much does lenacapavir cost?
Those of us who treat HIV were eagerly waiting to see what the medicine company would charge. Unfortunately, the cost turned out to be $14,109 per dose, which is over $28,000 a year.
Medicaid added lenacapavir to the formulary, which was a relief, but some pharmacies say it’s too expensive to stock right now.
Is there a generic?
There isn’t a generic version for lenacapavir. But to give the company credit, they are committed to making it cheaper for low- and middle-income countries.
The manufacturer is letting generic companies do something called voluntary licensing. This allows other companies to make and give out lenacapavir more cheaply in the future, which is heartening.
But in higher-income countries, like the U.S, I'm worried that some pharmacies or private insurance companies may find the price too high and refuse to stock it. We're going to have to see how this all plays out.
What’s your overall impression of lenacapavir as a PrEP option?
As someone who treats and works to prevent HIV, I’m excited about the lenacapavir shot because it seems easy. With the lenacapavir shot, it’s an every-six-month injection compared to a daily pill.
Even though you have to go to a clinic to get the shot, we find that PrEP adherence (sticking to treatment) is much higher.
Future HIV PrEP outlook
I would like a new formulation someday that could be injected deeper into the muscle. That way, we don't get those nodules.
The company is working on that.
As an HIV doctor, I was also unhappy about the price. But all together, I'm very excited about the potential for a long-acting treatment and prevention.
