Lenacapavir (Yeztugo): The Twice-Yearly PrEP Injection
PrEP used to mean a pill every day. Then it meant a shot every two months. As of mid-2025, it can mean two injections every six months — and in its pivotal trials, the newest option came about as close to perfect as prevention gets.
The short version
- Yeztugo (lenacapavir) is the first twice-yearly PrEP option, FDA-approved in June 2025 for adults and adolescents weighing at least 35 kg.
- In the PURPOSE trials it was remarkably effective: zero infections in the trial of cisgender women, and only two infections among more than 2,000 participants in the second large trial.
- The catch: it requires an in-office visit with an HIV test before every dose, and insurance coverage for the newest option is still catching up.
How the dosing actually works
Yeztugo is a subcutaneous (under-the-skin) injection given by a healthcare provider. Starting it takes two days: on day one you receive two injections plus two oral tablets in the office, and on day two you take two more tablets at home. After that, it's simply two injections every six months — with a two-week grace window on either side of the scheduled date. The day-one pills aren't about safety; they get protective drug levels up quickly instead of waiting for the injection to build.
What the trials showed
The PURPOSE 1 trial, conducted in cisgender women in sub-Saharan Africa — a population where PrEP pills have historically struggled with adherence — recorded zero HIV infections among participants receiving lenacapavir. PURPOSE 2, which enrolled gay and bisexual men and transgender and nonbinary people, recorded only two infections among more than 2,000 participants. The CDC issued formal clinical recommendations for lenacapavir PrEP in 2025. For comparison across all the options, see how effective PrEP is overall.
Yeztugo vs Apretude: the two injectables
| Yeztugo (lenacapavir) | Apretude (cabotegravir) | |
|---|---|---|
| Schedule | Every 6 months | Every 2 months |
| Injection type | Subcutaneous (abdomen) | Intramuscular (gluteal) |
| Start-up | Day 1 injections + pills, day 2 pills | Two injections one month apart |
| Evidence | PURPOSE 1 & 2: near-complete protection | HPTN trials: beat daily oral PrEP |
| Clinic visits per year | 2 | 6 |
| FDA approval | 2025 | 2021 |
Neither is "better" in a head-to-head sense — no trial has compared them directly. Two visits a year versus six is a real lifestyle difference, but Apretude has a multi-year head start on real-world availability and insurance pathways. One naming caution: both are sometimes confused with Cabenuva, which is HIV treatment, not PrEP.
Side effects to expect
The most common by far are injection-site reactions: soreness, redness, and a palpable bump or nodule under the skin that can take a while to fade — most people consider it a fair trade for six months of protection. Headache and nausea show up in a minority. As with every PrEP option, a confirmed negative HIV test is required before each dose, because giving a single-drug prevention agent to someone with undiagnosed HIV can breed resistant virus.
Cost and availability in 2026
Yeztugo is a brand-new specialty medication, and the honest picture is: coverage is evolving. PrEP as a category is supposed to be covered with no cost-sharing under ACA preventive rules, and Gilead runs assistance programs for people who fall through the cracks — but real-world reimbursement for the newest option tends to lag the first year or two. If cost is your deciding factor today, generic Truvada at $20–30/month and the other paths to $0 PrEP remain the most reliable routes, with injectables following as coverage matures.
Who it's a great fit for
Anyone who wants the fewest possible clinic visits, struggles with daily pills, values discretion (nothing at home, nothing in a cabinet), or simply wants the longest-acting protection that exists. If that sounds like you, start with a telehealth consult — we'll map which of the four PrEP options actually fits your life, and handle the lab work either way.