The FDA approved Yeztugo for HIV prevention on June 18, 2025. The drug is lenacapavir, a long-acting PrEP option from Gilead Sciences, and you get it as two injections under the skin every six months. It’s approved for adults and adolescents who weigh at least 35 kilograms (about 77 pounds) and are at risk of getting HIV through sex. You start with injections plus tablets over two days. Then you come back for a shot every 26 weeks.
In PURPOSE 2, 2 of 2,179 people on lenacapavir got HIV in the primary analysis. That trial enrolled cisgender men, trans women, trans men and nonbinary people. In trials, it works very well. It still isn’t a vaccine, and it comes with rules: an HIV test before every injection, a firm schedule and, for most people, a lump at the injection site that can last for months. Talk with a health care provider about whether it fits your situation. Nothing here is individual medical advice.
If PrEP is new to you, Gayety’s guide to PrEP pills and shots covers the basics. This page goes deep on Yeztugo.
Who Yeztugo Is Approved For
Yeztugo is indicated “to reduce the risk of sexually acquired HIV-1 in adults and adolescents weighing at least 35 kg who are at risk for HIV-1 acquisition,” according to the current FDA-approved prescribing information. Its last revision came in August 2026. You have to test HIV negative before the first dose. Gender doesn’t appear anywhere in that wording.
PURPOSE 1 studied cisgender adolescent girls and young women ages 16 to 25 in South Africa and Uganda. PURPOSE 2 cast a wider net, enrolling people 16 and older in Argentina, Brazil, Mexico, Peru, South Africa, Thailand and the United States. Per the label, about 22% of PURPOSE 2 participants identified as transgender women, transgender men or nonbinary.
The CDC weighed in with a September 2025 clinical recommendation. It says the every-six-months shot is “strongly recommended as a PrEP option in persons weighing ≥77 lbs (≥35 kg) who would benefit from PrEP.” Some groups come with caveats:
- People who inject drugs. The label covers sexually acquired HIV only. On injection drug use, the CDC says “additional research is needed to understand LEN’s effectiveness in persons who inject drugs.”
- Pregnancy. After a shared decision with a clinician, lenacapavir PrEP “may be used in pregnant women or continued in women who become pregnant while receiving injections,” according to the CDC. PURPOSE 1 data haven’t shown a drug-associated risk, the label says, though the numbers are small.
- Breastfeeding. Lenacapavir does pass into breast milk. The label asks clinicians to weigh the benefits of breastfeeding and PrEP against possible effects on the baby.
The Yeztugo Dosing Schedule, Day 1 to Month 6
The label is blunt about the start: efficacy “has only been established with this dosing schedule.” Every dose of the starting regimen counts.
| When | What happens | Fine print |
|---|---|---|
| Day 1 | Two 1.5 mL injections under the skin (927 mg total) plus two 300 mg tablets | HIV test that day or within the previous 7 days, per the CDC |
| Day 2 | Two more 300 mg tablets | If you miss them, take them as soon as possible. Never take the Day 1 and Day 2 tablets on the same day |
| Every 26 weeks | Two injections, counted from the date of the last injection | Window of 2 weeks early or late, with an HIV test before each injection |
| Delay expected beyond the window | A prescriber may switch you to one 300 mg tablet every 7 days | A temporary bridge for up to 6 months. Resume injections within 7 days of the last tablet |
| More than 28 weeks with no shot or bridge | Restart from Day 1 | A clinician first confirms you’re still HIV negative |
A health care provider gives the shots, usually in the belly. The thigh is the label’s alternative site. Intradermal injection, meaning into the skin itself, “has been associated with serious injection site reactions, including necrosis and ulcer,” the label warns. The August 2026 revision updated the injection instructions in section 2.6.
You can take the tablets with or without food. Tell every prescriber you’re on Yeztugo. Per the label, certain drugs that speed up liver enzymes (strong or moderate CYP3A inducers) mean you’ll need extra supplemental doses.
How Long Until Yeztugo Protects You?
Nobody knows exactly. In the label’s words, “the time from initiation of YEZTUGO for HIV-1 PrEP to maximal protection against HIV-1 infection is unknown.” The CDC’s review gets more specific, provided both days of tablets are taken: “Limited data suggest protective levels of LEN are achieved 2 hours after the dose on day 2.” Ask your clinic what backup to use in the meantime.
PURPOSE 1 and PURPOSE 2 Results in Plain Numbers
Gilead funded both trials. Each was randomized and double-blind, and each compared the shot with daily pills.
| Trial | Who enrolled | HIV infections on lenacapavir | HIV infections on daily Truvada (F/TDF) | Published |
|---|---|---|---|---|
| PURPOSE 1 | 5,338 cis women and girls, 16 to 25 | 0 of 2,134 | 16 of 1,068 | NEJM, Oct. 3, 2024 |
| PURPOSE 2 | 3,265 cis men, trans women, trans men and nonbinary people | 2 of 2,179 | 9 of 1,086 | NEJM, April 3, 2025 |
The label calls the PURPOSE 2 result “an 89% reduction in the risk of incident HIV-1 infection over TRUVADA.” HIV incidence on lenacapavir was 0.10 per 100 person-years. On Truvada it was 0.93. You’ll also see a 96% figure repeated a lot. That one compares lenacapavir with the estimated background HIV rate in screened participants (2.37 per 100 person-years), which is a different yardstick.
“Adherence to F/TAF and F/TDF was low,” the PURPOSE 1 paper says plainly. The pill arms struggled partly because people didn’t take their pills. Truvada taken as prescribed still works. The shot’s edge is that it doesn’t depend on a daily habit.
Zero didn’t stay zero. Later follow-up found 2 more infections in the PURPOSE 1 lenacapavir group, one in a person who had already stopped the drug. PURPOSE 2 had 1 more, according to the label and the CDC.
Yeztugo Side Effects: The Lumps, Explained
Most people feel the shot. Per the label, injection-site reactions hit 69% of lenacapavir recipients in PURPOSE 1 and 83% in PURPOSE 2. None were classed as serious, and most were mild or moderate.
Plan for the lump. In PURPOSE 1, 64% of participants on the drug got a nodule, a firm bump under the skin. In PURPOSE 2 it was 63%. Nodules from the first injections lasted a median of 350 days in PURPOSE 1 and 297 days in PURPOSE 2, which is longer than the gap between appointments. The typical largest nodule was about 3 centimeters across.
| Side effect (label, Table 6 and 7) | PURPOSE 1 | PURPOSE 2 |
|---|---|---|
| Any injection-site reaction | 69% | 83% |
| Nodule | 64% | 63% |
| Pain at injection site | 31% | 56% |
| Headache | 7% | 2% |
| Nausea | 5% | 2% |
| Stopped the drug because of injection-site reactions | 0.2% | 1.2% |
Skin biopsies from a separate lenacapavir treatment trial found “foreign body inflammation or granulomatous response” in some nodules, per the label. The CDC reports that grade 3 or higher adverse events, including injection-site reactions, ran slightly lower on lenacapavir than on Truvada in PURPOSE 2: 4.8% versus 6.1%. Ask your clinic how to tell an expected lump from worsening pain, skin breakdown or a problem that needs a look.
HIV Testing and the Yeztugo Resistance Warning
“Drug-resistant HIV-1 variants have been identified with use of YEZTUGO by individuals with undiagnosed HIV-1 infection,” reads Yeztugo’s boxed warning, the FDA’s strongest kind. One drug alone can’t treat HIV. So a person who already has the virus can develop resistance.
Testing is built into every visit for that reason. Before the first shot and before each injection, the label requires an FDA-approved test for acute HIV. A negative antigen/antibody result at the start should be confirmed with an RNA test, even if that result comes back after the first dose. At later injection visits, a negative rapid, point-of-care antigen/antibody result should be confirmed with a more sensitive test. “Oral HIV antibody tests should not be used because of their low sensitivity in detecting recent HIV infection,” the CDC adds.
In PURPOSE 2, all 3 people who got HIV after starting the drug had lenacapavir resistance mutations, per the label. If you’ve had a recent exposure or flu-like symptoms such as fever, rash or fatigue, tell your clinic. Anyone diagnosed with HIV moves to a full treatment regimen.
For global rollout, the WHO took a different line. Its July 14, 2025 guidelines recommended “a public health approach to HIV testing using HIV rapid tests” for long-acting PrEP. U.S. clinics follow the FDA label.
Stopping Yeztugo and the Long Drug Tail
Lenacapavir lingers. Residual drug “may remain in the systemic circulation of individuals for prolonged periods (up to 12 months or longer after the last subcutaneous dose),” the label says. Eventually it falls below protective levels. HIV picked up during that tail can become resistant.
If you stop and still need protection, the label says to consider another form of PrEP started within 28 weeks of your last injection. Drug interactions outlast the shots, too. Lenacapavir can raise levels of some medicines started up to 9 months after the last injection, so tell every prescriber and pharmacist.
What Yeztugo Costs and How Insurance Works in 2026
Gilead’s current U.S. price page lists $29,036.32 for a year of injections, plus $2,419.69 for the starting tablets. Those figures are dated June 29, 2026, and replace the $28,218 annual injection price reported at launch. List price isn’t your bill. Your costs depend on insurance, clinic charges and assistance eligibility.
| Your coverage | What to know |
|---|---|
| Commercial insurance | Gilead’s Advancing Access co-pay program says eligible commercially insured patients “could pay as little as $0.” Ask about prior authorization and whether it’s billed as a pharmacy or medical benefit |
| Uninsured | Gilead says its medication assistance program provides Yeztugo free to eligible uninsured patients. Ask separately about visits and lab costs |
| Medicare | Part B covers injectable lenacapavir PrEP with no deductible or copay, per a CMS fact sheet updated Feb. 25, 2026. The provider or pharmacy must bill Part B |
| Medicaid | State Medicaid programs must cover it, though rules and prior authorization vary by state, according to a March 2026 NASTAD implementation guide |
Does the ACA Require $0 Coverage for Yeztugo?
As of November 2026, that’s unsettled. Under the Affordable Care Act, most plans have to cover services with an “A” or “B” grade from the U.S. Preventive Services Task Force without cost sharing. The task force gave PrEP an A grade in August 2023, before Yeztugo existed. That recommendation doesn’t name specific drugs.
A March 2026 NASTAD guide describes insurers interpreting the recommendation differently. Some treat it as covering all effective PrEP drugs. Others rely on the drugs reviewed before Yeztugo’s approval. Ask your clinic to check both medical and pharmacy benefits, then get an estimate covering the medication, visits and tests.
Formularies have widened. CVS Health first refused to cover Yeztugo, then reversed course in January 2026, according to the HIV+Hepatitis Policy Institute. “However, coverage does not automatically translate into access and usage,” Carl Schmid, the institute’s executive director, warned. At one St. Louis clinic, Gayety reported, about 4 in 10 patients prescribed injectable PrEP never started it, mostly because of insurance problems.
There’s no cheaper U.S. version yet. On Nov. 2, 2026, Unitaid announced that Dr. Reddy’s had won FDA tentative approval for a generic lenacapavir, priced at $40 a year for 120 low- and middle-income countries. As Gayety explained, tentative approval doesn’t allow U.S. sales while Gilead’s patents stand.
Yeztugo vs. Apretude: Comparing PrEP Shots
Both are long-acting injections. They’re also different drugs on different schedules.
| Feature | Yeztugo (lenacapavir) | Apretude (cabotegravir) |
|---|---|---|
| Maker | Gilead | ViiV Healthcare |
| Where it goes | Under the skin, belly or thigh | Into the buttock muscle |
| Starting doses | Injections plus tablets on Days 1 and 2 | Two injections one month apart |
| Then | Every 6 months | Every 2 months |
| First U.S. approval | June 2025 (as Yeztugo) | 2021 |
The Apretude details come from its prescribing information. No head-to-head trial has compared the two shots. Side effects, drug interactions, testing and coverage can all tip the choice. That’s a conversation for you and your provider.
Weekly Pill and Once-Yearly Lenacapavir: What’s Coming
Gilead has two new versions in the pipeline. Neither is approved.
The FDA accepted Gilead’s application for once-weekly oral Yeztugo as PrEP, the company announced June 15, 2026, with a decision date of Feb. 2, 2027. “HIV prevention is not one-size-fits-all,” said Dietmar Berger, Gilead’s chief medical officer. Weekly tablets are already in the current label, but only as a short bridge when a shot is delayed.
A once-yearly intramuscular shot is further back. On Sept. 16, 2026, Gilead said its Phase 3 PURPOSE 365 study is ongoing and that the yearly version hasn’t been approved anywhere.
The WHO has backed the twice-yearly shot globally since July 2025. “While an HIV vaccine remains elusive, lenacapavir is the next best thing,” WHO Director-General Tedros Adhanom Ghebreyesus said at the time.
Questions to Ask Before Your First Yeztugo Shot
- Is Yeztugo on my plan, and is it billed under the pharmacy or medical benefit?
- Will I owe anything for the visit, the injection or the lab tests?
- Who gives the shots, and can I book my 26-week appointment today?
- What’s my plan if I’m traveling when my window closes?
- Do any of my current medicines interact with lenacapavir?
Yeztugo doesn’t prevent syphilis, gonorrhea or chlamydia. The label pairs it with condoms and regular STI testing. For a firsthand view, read Gayety’s Yeztugo one year later with Dr. Howard Grossman.
Yeztugo PrEP Shot FAQ
How effective is Yeztugo?
None of the 2,134 cis women on lenacapavir in PURPOSE 1 got HIV in the primary analysis. In PURPOSE 2, 2 of 2,179 did, an 89% lower rate than daily Truvada. Even so, the label warns that Yeztugo “is not always effective in preventing HIV-1 acquisition.”
How often do you get the Yeztugo shot?
Every six months (26 weeks), within a two-week window either way. That follows a two-day start of injections and tablets.
Where is Yeztugo injected?
A health care provider injects it under the skin of the belly. The thigh is an alternative.
Do Yeztugo injections leave lumps?
Usually. About 63% to 64% of trial participants on the drug got a nodule. Nodules from the first shots lasted a median of 297 to 350 days.
How much does Yeztugo cost?
Gilead lists annual injections at $29,036.32, with another $2,419.69 for the starting tablets. Your out-of-pocket cost depends on coverage and assistance eligibility. Ask for a benefits check before your first visit.
Is Yeztugo free under the ACA?
Not automatically. Some plans cover it at $0 as preventive care. Others charge cost sharing, because the 2023 task force recommendation doesn’t name it.
Can women use Yeztugo?
Yes. PURPOSE 1 tested it in cisgender women and girls. The FDA indication doesn’t depend on gender.
Is there a generic Yeztugo?
Not in the U.S. A generic from Dr. Reddy’s has FDA tentative approval, but only for use in low- and middle-income countries.
Is there a once-a-year PrEP shot?
Not yet. Gilead’s once-yearly lenacapavir is still in Phase 3 testing. A weekly lenacapavir pill faces an FDA decision by Feb. 2, 2027.
