YEZTUGO (lenacapavir): the first semi-annual injectable PrEP against HIV — dosage, price and how it works

If you have seen an advertisement that promises «twice-yearly HIV prevention» with two injections every six months, you are probably talking about YEZTUGO (lenacapavir), the drug from Gilead Sciences that in June 2025 became the first and only semi-annual injectable PrEP approved by the FDA in the United States. The subcutaneous injection of 463.5 mg in 1.5 mL replaces the daily pill for those who prefer two visits a year. In July 2026 the One2PrEP campaign continues on television, networks and dating apps. This guide explains what it is, how it is administered, what the PURPOSE trials showed, how much it costs, and what limitations it has.

What is YEZTUGO and what is it for?

YEZTUGO is a prescription medication indicated as PrEP (pre-exposure prophylaxis): it reduces the risk of contracting HIV-1 sexually in adults and adolescents who weigh at least 35 kg (77 pounds) and are at risk of exposure. It does not treat HIV or prevent other sexually transmitted infections (STIs): condoms and regular testing are still part of the prevention plan.

The active ingredient is lenacapavir, an HIV-1 capsid inhibitor that Gilead was already using in treatment (as Sunlenca). The PrEP formulation arrives in prefilled syringes of 463.5 mg/1.5 mL for subcutaneous administration in a doctor's office.

"You must be HIV negative before and while receiving YEZTUGO." — official product information.

Dose schedule: initiation and maintenance

YEZTUGO is not “one shot and done”: it requires a start-up period with injections and oral tablets, and then moves to a six-month schedule. According to the FDA label and YEZTUGO.com:

Phase	Day	What is administered
Home	Day 1	927 mg SC (2 × 1.5 mL injections) + 600 mg oral (2 × 300 mg tablets) in office
	Day 2	600 mg oral (2 × 300 mg tablets) at home
Maintenance	Every 6 months	927 mg SC (2 × 1.5 mL injections), with a window of ±2 weeks from the last dose

In practice, that means two office visits per year (after completion of initiation), with two injections per visit. Missing appointments or skipping initial tablets increases the risk of infection; Gilead insists on attending all scheduled appointments.

Efficacy: PURPOSE 1 and PURPOSE 2 trials

The FDA approval was based on two Phase 3 trials, PURPOSE 1 (cisgender women in sub-Saharan Africa) and PURPOSE 2 (diverse population: cis men, cis women, and trans and non-binary people). In both, six-monthly lenacapavir was compared to daily oral Truvada (emtricitabine/tenofovir disoproxil fumarate).

• PURPOSE 1: no HIV infection among the 2,134 participants who received semiannual SC lenacapavir (100% reduction vs. background incidence and superiority vs. Truvada).
• PURPOSE 2: only two infections; ≥99.9% remained HIV negative at one year, with superiority compared to the daily pill.

Gilead highlights that, in PURPOSE 2 surveys, 89% of those who received injections preferred that format compared to 11% who preferred the daily pill — a central argument of the One2PrEP campaign.

Important warnings

The label includes a black box (boxed warning): if a person is HIV positive and only receives YEZTUGO (without complete antiretroviral treatment), they may develop drug resistance that complicates future treatment. That is why HIV tests are mandatory before starting, before each injection and when the doctor indicates it.

Other key security points:

• If you suspect recent exposure or flu-like symptoms (fever, fatigue, ganglia), tell your doctor: they could indicate acute HIV infection.
• Most frequent adverse effects: reactions at the injection site, headache and nausea.
• In rare cases, poor injection technique can cause serious skin lesions.
• Lenacapavir remains in the body for up to 9 months after the last dose and may interact with other medications.

Price and coverage in the United States

The list price (WAC) of the injectable component is around $28,218 per year in the maintenance year, according to Gilead Price Information. The starting year also adds about $2,351.50 in oral tablets. That amount is not what most pay: Gilead's Advancing Access program can reduce the copay to 0–$5 for patients with eligible commercial insurance, and offers free assistance to those without coverage.

As of July 2025, CMS approved Medicare coverage without cost-sharing for eligible beneficiaries. Administration is done in the office (buy-and-bill) or via authorized specialized pharmacies; The doctor arranges prior authorization if the plan requires it.

How does it compare to other PrEP options?

Option	Frequency	Notes
YEZTUGO (lenacapavir)	2 injections / 6 months	First biannual PrEP; requires oral + injectable starting dose
Apretude (cabotegravir)	Monthly or bimonthly	Long-acting injectable; already approved for PrEP since 2021
Descovy / Truvada	1 tablet / day	Standard oral PrEP; Generics available

Availability outside the US.

As of July 2026, YEZTUGO is commercially approved in the United States. Gilead has submitted applications to the EMA (accelerated evaluation), as well as in Australia, Brazil, Canada and South Africa, and is preparing registrations in Argentina, Mexico and Peru based on FDA approval. In Latin America and Europe there is still no general marketing; It is advisable to consult with a local infectious disease specialist regarding available PrEP alternatives.

Is YEZTUGO right for you?

Only a healthcare professional can determine if YEZTUGO fits your situation: they will assess the risk of exposure, medical history, pregnancy or breastfeeding, interactions with other drugs, and the logistics of attending semiannual injections. If the ad has caught your attention, the first step is a conversation with your doctor and a negative HIV test — it is not a substitute for personalized clinical advice.

For more official information: What is YEZTUGO? · Coverage and cost · telephone 1-844-YEZTUGO (USA).