For years, HIV prevention meant a pill every day. That is no longer the only choice. A long-acting injection given just twice a year is now FDA-approved for HIV pre-exposure prophylaxis (PrEP) in the United States. Here is how the twice-yearly shot works, who can get it, what it may cost and how insurance coverage works.
What is the twice-yearly HIV prevention shot?
The twice-yearly shot is lenacapavir, sold under the brand name Yeztugo. The FDA approved it in June 2025 for adults and adolescents who weigh at least 35 kg (about 77 lb), do not have HIV and want to lower their risk of getting HIV through sex.
After a short start-up phase, the medication is given as injections under the skin once every six months. That means two clinic visits a year for the shot itself, instead of remembering a daily pill.
How effective is it?
In large clinical trials, lenacapavir was highly effective at preventing HIV. In one trial in cisgender women, no participants who received the injection acquired HIV. In another trial in men and gender-diverse people, infections were very rare and lower than in people taking daily oral PrEP.
As with any PrEP, protection depends on staying on schedule. Missing a six-month dose can leave you without protection, so keeping appointments matters.
How does starting the shot work?
- HIV test first: you need a negative HIV test before starting. Using PrEP during an undiagnosed HIV infection can lead to drug resistance.
- Start-up phase: the first dose includes injections plus oral tablets taken on the first two days.
- Every six months: after that, injections are given once every six months by a healthcare professional.
- Regular testing: HIV testing continues at follow-up visits while you remain on PrEP.
How does it compare with other PrEP options?
- Daily pills: oral PrEP taken every day at home. A low-cost generic is available.
- Every-two-month injection: cabotegravir (Apretude) is given by injection every two months after two starter doses one month apart.
- Twice-yearly injection: lenacapavir (Yeztugo) is given every six months after the start-up phase.
The best option depends on your routine, how often you can attend appointments, your medical history and your insurance. A clinician can help you compare them.
How much does the twice-yearly shot cost?
The list price of lenacapavir for PrEP is about $28,000 per year before insurance. Most people do not pay the list price. What you actually pay depends on your insurance plan, whether the plan covers the medication and the injection visit, and whether you qualify for assistance.
Does insurance cover it?
Under the Affordable Care Act, most private health plans must cover recommended preventive services, including PrEP, without copays or deductibles. In June 2025 the US Supreme Court upheld that requirement.
Coverage of a specific product can still vary. Some insurers and pharmacy benefit managers took time to add the new shot to their drug lists, and some plans require prior authorization. Before starting, ask your insurer:
- Is lenacapavir (Yeztugo) on the plan's drug list for PrEP?
- Is prior authorization required?
- Are the injection visit, HIV tests and lab work covered at no cost?
- Which clinics or pharmacies are in network for the injection?
What if you don't have insurance?
Uninsured people may qualify for the manufacturer's patient assistance program, which can provide the medication at no cost to eligible people based on income. Community health centers, sexual health clinics and some state PrEP assistance programs can also help with visits and testing. Daily generic oral PrEP is another low-cost option if the shot is not accessible.
Possible side effects
The most common side effects are injection-site reactions, such as swelling, pain, redness or a small lump under the skin, which can last for some time. Nausea and headache have also been reported. Tell your provider about all medications you take, since some can interact with lenacapavir.
Important to know
- PrEP does not protect against other sexually transmitted infections or pregnancy.
- If you had a possible HIV exposure in the last 72 hours and were not protected, seek urgent care about post-exposure prophylaxis (PEP).
- Do not start, stop or switch PrEP without talking to a healthcare professional.
The bottom line
The twice-yearly HIV prevention shot gives people a highly effective option that needs only two injections a year after a short start-up. Check your insurance coverage, ask about assistance if you are uninsured, and talk to a clinician about whether it suits you.
This article is for general information only and is not medical advice. Talk to a qualified healthcare professional about your individual situation.