How Yeztugo (Lenacapavir) Works With Just 2 Doses Per Year

Two appointments. Twelve months of protection against HIV. 

That’s what’s got people talking about Yeztugo (lenacapavir), the new FDA-approved injectable PrEP that protects against HIV for a full six months with a single dose.

Bold claim? Absolutely, but the proof’s in the data. We’ll explain how Yeztugo works, what the trials found, and how it compares to more familiar PrEP options.

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How HIV infections happen

HIV doesn’t infect someone the moment they’re exposed to it. For an HIV infection to happen, the virus needs to both enter your body, enter specific cells, integrate into the genetics of those cells, and then make copies of itself.

Once HIV enters your bloodstream, the virus makes a beeline for your T cells, which are cells in your immune system that usually fight infections. Once the virus breaks into them, however, they become HIV-copying machines. 

The virus fills the T cell with copies of itself until the cell literally bursts, spreading those copies to more T cells to continue the cycle and overwhelm the immune system and its ability to fight any other kind of infection.

Prevent the virus from making copies of itself, and you prevent the infection. That’s what all forms of PrEP are designed to do. Yeztugo just does it a bit differently.

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How Yeztugo (lenacapavir) prevents HIV, six months at a time

Yeztugo (lenacapavir) belongs to a newer class of HIV medication called capsid inhibitors. Unlike other forms of PrEP that work on a single point of the HIV replication cycle, specifically genetic replication, capsid inhibitors block several steps in this cycle by targeting a key component of the virus called the capsid.

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The capsid’s job

HIV travels inside a cone-shaped protein shell called the capsid. The capsid both protects the virus and carries the genetic “instructions” needed for it to copy itself.

For HIV to spread, the virus’s shell has to:

• Break into the T cell
• Slip into the T cell’s command center (the nucleus)
• Open itself and release the genetic instructions
• Repackage itself in a new capsid for further spread

Simply put, the capsid plays a key role in every step of the HIV infection cycle. Yeztugo is designed to disrupt it.

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Where Yeztugo (lenacapavir) steps in

The active ingredient, lenacapavir, latches onto the shell’s proteins and reshapes them. It’s a bit like filing down the grooves of a key so it no longer fits the lock. Without the right fit, HIV can’t enter the cell or use it to create copies of itself. It also can’t put itself back together. 

Here’s how that translates into twice-yearly dosing:

• It strikes early: Yeztugo targets the virus’s shell as soon as it shows up, shutting it down before it can latch onto your cells.
• It blocks the virus twice: Lenacapavir steps in at two points: before HIV locks into a cell’s DNA and after it’s already slipped inside — like locking the door and welding it shut.
• It sticks around: Yeztugo is delivered in a high dose that’s injected just beneath your skin, and releases slowly into your bloodstream over six months, providing consistent protection.

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What the research says about Yeztugo (Lenacapavir)

Lenacapavir isn’t new to HIV care — it’s also called Sunlenca, an FDA-approved treatment for people living with HIV. What’s new is its role in prevention. That green light came earlier this year, after two large PURPOSE trials showed just how well it works:

• PURPOSE 1: Over 2,100 cisgender women in Africa received Yeztugo. None contracted HIV during six months of follow-up, compared to 1.82% on Descovy and 1.5% on Truvada (NEJM, 2024). 
• PURPOSE 2: Over 2,200 gay, bi, trans, and non-binary participants in multiple countries received Yeztugo. Just 0.09% got HIV, compared to 0.82% on daily Truvada (NEJM, 2024).

Does that make Yeztugo more effective than daily pills? Not exactly. The difference comes down to consistency. With pills, you’re aiming for 365 perfect days in a row — a tough streak for anyone to keep. Twice-yearly shots require just two clinic visits, and in trials, 92% of people made both right on schedule. 

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Comparing Yeztugo with other HIV PrEP options

All HIV prevention methods work toward the same goal: to stop the virus before it can make enough copies of itself to cause an infection. The difference is when they jump in, how they do it, and how long that protection lasts.

Daily PrEP pills (Truvada, Descovy): 

• How it works: Sneaks into HIV’s DNA chain during the copying process and shuts it down from within.
• Timing: One pill, every day.
• Effectiveness: 99% effective when taken as prescribed.

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Injectable PrEP Apretude:

• How it works: Blocks the integrase enzyme HIV needs to copy itself and spread in the body.
• Timing: One injection every two months, with an extra dose one month after your first.
• Effectiveness: 99%+ when taken as prescribed.

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Injectable PrEP (Yeztugo)

• How it works: Reshapes HIV’s protective shell to block it at multiple stages of its life cycle.
• Timing: One injection every six months, plus two starter pills before your first injection. 
• Effectiveness: 99-100% when taken as prescribed.

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Yeztugo curious?  

All forms of PrEP work extremely well when you stick to the schedule. The key is finding the one that fits your life best. For many, that will continue to be daily PrEP pills. But for people who face challenges taking pills daily for any reason, injectable PrEP, including Yeztugo, could provide more effective protection.

As Yeztugo is new, coverage from health insurance providers is still limited, but that’s likely to change in the near future. It’s worth considering other options to stay protected against HIV, like daily PrEP pills, while waiting for Yeztugo to become more available.

A Freddie clinician can help you understand your options for PrEP, today and in the future — and booking an online appointment is free.

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