What Is Lenacapavir?

Imagine protecting yourself from one of the world’s most consequential viruses with just two injections a year. That is exactly what lenacapavir — brand names Sunlenca and Yeztugo — promises to do, and so far the science is backing it up spectacularly.

Lenacapavir (chemical name GS-6207) is a first-in-class HIV capsid inhibitor developed by Gilead Sciences. It was FDA-approved in December 2022 for the treatment of multidrug-resistant HIV, and then in June 2025 for HIV prevention (PrEP) — making it one of the most versatile antiretrovirals ever developed.

What sets lenacapavir apart from virtually every other HIV medication on the market is its extraordinary half-life. Because it stays in the body at therapeutic concentrations for months, patients only need an injection every six months — a landmark shift from the daily pill-taking that has defined HIV care for decades.

“Oral regimens have transformed HIV care, but taking a pill every day is difficult. Longer-acting options relieve the burden of daily pill-taking and have the potential to improve adherence, improve virologic control, and reduce new infections.” — Dr. Amy Colson, Community Resource Initiative, Boston (CROI 2024)

In 2024, Science magazine named lenacapavir its “2024 Breakthrough of the Year,” citing what it called “astonishing 100% efficacy” in one large prevention trial among women, and 99.9% efficacy in gender-diverse populations — numbers that are almost without precedent in the history of infectious disease prevention.

How Does It Work? (Mechanism of Action)

To understand why lenacapavir is so revolutionary, it helps to know a bit about how HIV operates inside the human body.

When HIV infects a cell, it relies on a protein shell called the capsid — essentially a protective case that carries the virus’s genetic blueprint. The capsid plays critical roles at multiple stages of the viral life cycle: it helps HIV sneak its DNA into the cell’s nucleus, assists the virus in replicating, and helps new viral particles assemble properly before budding off to infect more cells.

Lenacapavir works by binding directly to the interface between HIV-1 capsid protein (p24) subunits, essentially jamming multiple gears of the viral machine simultaneously. Specifically, it:

• Over-stabilizes the capsid — preventing it from releasing its genetic cargo once inside the cell
• Blocks nuclear uptake — stopping HIV’s DNA from making it into the cell nucleus
• Disrupts virus assembly and release — interfering with the construction of new viral particles
• Interferes with capsid core formation — sabotaging the virus at its very origin

Because lenacapavir attacks HIV at multiple points simultaneously, it retains activity against virus strains that have developed resistance to other drug classes — including NRTIs, NNRTIs, protease inhibitors, and integrase inhibitors. That multi-step mechanism is also why resistance to lenacapavir is relatively difficult to develop when the drug is used correctly.

Brand Names: Sunlenca vs. Yeztugo — What’s the Difference?

You will hear lenacapavir referred to by two brand names in the United States, and understanding which is which matters:

Both are the same molecule — lenacapavir — just approved for different purposes. Internationally, the EU approved Sunlenca for treatment in August 2022 and Yeytuo (slightly different spelling) for PrEP prevention in September 2025. The drug was also approved in Canada in November 2022. The World Health Organization (WHO) recommended lenacapavir for PrEP in 2025, and it has since been prequalified for global use.

Clinical Trial Results That Shocked the World

The science behind lenacapavir is not just impressive — it is genuinely historic. Let us walk through the key trials that built the evidence base.

CAPELLA Trial (Treatment)

This was the pivotal trial that led to lenacapavir’s first approval. Among 72 adults with multidrug-resistant HIV who were failing other regimens, lenacapavir combined with an optimized background regimen achieved significant viral load reductions. Importantly, participants maintained viral suppression for up to 52 weeks.

PURPOSE 1 (PrEP — Cisgender Women)

Conducted among approximately 5,000 cisgender women in South Africa and Uganda, this Phase III trial produced an incidence rate ratio of 0.00 — meaning not a single woman in the lenacapavir group contracted HIV during the study period. The 95% confidence interval was 0.00–0.04 (p<0.001). This was the result that electrified the global health community.

PURPOSE 2 (PrEP — Broader Populations)

A second Phase III study examined lenacapavir’s efficacy in a broader group including men who have sex with men, transgender women, transgender men, and gender non-binary individuals. The incidence rate ratio was 0.04 (95% CI: 0.01–0.18, p<0.001) — a 96% reduction compared to background HIV incidence. Injection site reactions led to discontinuation in only 1.2% of patients.

Weekly Oral Islatravir + Lenacapavir (Phase II)

Looking ahead, Gilead and Merck are collaborating on a once-weekly oral combination of islatravir plus lenacapavir. In a Phase II trial, 94% of people who switched to this weekly combination maintained an undetectable viral load — matching the performance of daily Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide). If larger Phase III data confirm this, it could become the longest-acting oral HIV regimen ever, with no injections required.

Dosage and How It Is Given

One of the things people worry about with a new drug is how complicated the regimen is. With lenacapavir, the answer is: surprisingly simple — after the initial loading phase.

For HIV Treatment (Sunlenca)

There are two initiation options, both designed to build up drug concentrations quickly before transitioning to a maintenance schedule. According to the Mayo Clinic drug reference:

• Option 1: Subcutaneous injection of 927 mg (two 1.5 mL injections) on Day 1, plus oral lenacapavir 600 mg on Days 1 and 2 — then a maintenance injection every 26 weeks (±2 weeks).
• Option 2: Oral lenacapavir 600 mg on Days 1 and 2, then 300 mg on Day 8, then a subcutaneous injection of 927 mg on Day 15 — followed by maintenance every 26 weeks.

Lenacapavir for treatment is never used as monotherapy — it is always combined with an optimized background regimen of other antiretrovirals.

For HIV Prevention / PrEP (Yeztugo)

The PrEP regimen is elegantly simple: two subcutaneous injections in the abdomen on the first visit, plus two oral tablets on Day 1 and two more on Day 2 (the “oral loading dose”). After that, injections every six months. Read more about the lenacapavir PrEP regimen at PrEPWatch.

Who Can Use Lenacapavir?

Whether lenacapavir is right for you depends on your HIV status, your medical history, and your goals. Here is how it breaks down:

Lenacapavir for HIV Treatment

You may be a candidate for Sunlenca (lenacapavir for treatment) if you are an adult living with HIV who:

• Has previously received other HIV medicines
• Has HIV that is resistant to several classes of antiretrovirals
• Is currently experiencing treatment failure — meaning your current regimen is not suppressing the virus
• Cannot tolerate other options due to side effects or safety concerns

Lenacapavir for HIV Prevention (PrEP)

According to CDC PrEP guidelines, Yeztugo is appropriate for:

• HIV-negative adults and adolescents weighing at least 77 pounds (35 kg)
• People at risk of sexually acquired HIV-1
• Those who prefer an injection over daily pills
• People for whom adherence to daily oral PrEP has been a challenge

You must have a confirmed negative HIV test before starting lenacapavir for PrEP. The NIH’s PrEP fact sheet explains that starting any PrEP drug while unknowingly HIV-positive can cause drug resistance, so testing is non-negotiable.

People who are pregnant should discuss the risks and benefits with their healthcare provider. Current data show no significant interaction between lenacapavir and oral contraceptives or gender-affirming hormone therapy — an important consideration for transgender patients. For more on managing health alongside complex legal and personal matters, see Ilastia’s resources.

Side Effects and Safety Profile

No drug is perfect, and lenacapavir does come with a side effect profile — though it is notably mild for most users.

Common Side Effects

The most frequently reported side effects, based on clinical trial data, include:

• Injection site reactions — pain, swelling, redness, skin hardening, or a small lump under the skin. These are the most common complaints and are usually mild.
• Nausea — typically mild and often resolves over time.
• Headache — reported especially with the Yeztugo PrEP formulation.

Rare but Serious Concerns

Lenacapavir is generally well-tolerated, but tell your doctor right away if you experience severe injection site reactions, signs of liver problems, or any new symptoms that concern you. The HIV i-Base patient guide on lenacapavir provides an in-depth look at monitoring and safety.

In clinical trials for PrEP, injection site reactions led to discontinuation in only 0.2% of patients in PURPOSE 1 and 1.2% in PURPOSE 2 — very low rates compared to the benefit.

Drug Interactions to Know

Lenacapavir is metabolized by the liver, which means some medications can raise or lower its levels in your body. This is critically important information to share with every prescriber you see.

Always give your doctor and pharmacist a complete list of everything you take — prescription drugs, over-the-counter medications, supplements, and herbal products. For a comprehensive drug interaction overview, see the HIV i-Base lenacapavir guide.

For anyone navigating a complex healthcare situation — whether managing chronic illness, dealing with insurance coverage disputes, or handling a medical-legal matter — Ilastia covers all of these topics in depth.

Lenacapavir vs. Cabotegravir for PrEP: Which Is Right for You?

If you are considering long-acting injectable PrEP in the United States, you now have two options: cabotegravir (Apretude), approved since 2021, and the newer lenacapavir (Yeztugo). Here is how they compare:

The biggest practical advantage of lenacapavir is its twice-yearly schedule — you only need to visit a clinic twice a year versus six times for cabotegravir. For many people, especially those with demanding schedules or limited healthcare access, this difference is enormous. The HIV Guidelines Program provides a thorough clinical comparison of all PrEP options, including how to manage missed injections for each.

Cost, Insurance Coverage, and Global Access

One of the most important conversations happening around lenacapavir right now is not about its science — it is about its price and global accessibility.

Cost in the United States

Gilead Sciences set the U.S. list price for Yeztugo at approximately $28,218 per year in 2025 — substantially less than the first-year Sunlenca treatment price of $42,250. Most major insurance plans and Medicaid are required to cover PrEP under the Affordable Care Act (ACA) without cost-sharing. Gilead also offers a $0 copay program for eligible commercially insured patients.

If you are uninsured, the HIV Services Locator (HIV.gov) can connect you with local programs offering subsidized PrEP. Many states also have their own PrEP assistance programs.

Global Access: The $40-Per-Year Breakthrough

In low- and middle-income countries, the price story is radically different — and rapidly improving. In October 2024, Gilead granted voluntary licenses to six generic manufacturers, including Dr. Reddy’s Laboratories, to supply lenacapavir across 120 low- and middle-income countries.

“Securing a US$40 price for the twice-yearly lenacapavir injection for PrEP is a historic breakthrough that proves the most advanced tools can be made affordable from the very start.” — Dr. Philippe Duneton, Executive Director, Unitaid

Through an agreement announced at the Clinton Global Initiative and led by CHAI (Clinton Health Access Initiative), Unitaid, and the Gates Foundation, the annual cost of the injection will be brought to just $40, with the oral loading course costing no more than $17. By 2027, this could make lenacapavir as affordable as existing daily oral PrEP options in developing nations.

PEPFAR and the Global Fund have committed to procuring lenacapavir for up to 2 million people in low- and middle-income countries — a procurement scale that public health experts say is essential to making a real dent in the global HIV epidemic.

The Future: Once-Weekly Pills, New Combinations, and What’s Coming

The story of lenacapavir is still very much being written. Here are the most exciting developments on the horizon.

Once-Weekly Oral Lenacapavir + Islatravir

The collaboration between Gilead and Merck on a once-weekly oral combination of islatravir and lenacapavir is among the most closely watched developments in HIV medicine. Islatravir (MK-8591) is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) with its own unusually long half-life — making it a perfect pharmacokinetic partner for lenacapavir. Phase II data from CROI 2024 showed 94% of participants maintaining undetectable viral loads at 24 weeks on the weekly oral regimen. Phase III trials are underway.

Lenacapavir + Bictegravir Single-Tablet Regimen

Gilead is also exploring a fixed-dose combination tablet that pairs lenacapavir with bictegravir — the integrase inhibitor anchor of the popular daily regimen Biktarvy. If approved, this single-tablet regimen could dramatically expand treatment options for people with HIV who need a simpler, more potent approach.

Neutralizing Antibody Combinations

For virally suppressed individuals switching treatment, early studies have tested lenacapavir injections combined with infusions of broadly neutralizing antibodies (bNAbs) — specifically teropavimab and zinlirvimab. This all-injectable, antibody-based approach represents a potentially transformative direction for long-term HIV management.

Doravirine/Islatravir (DOR/ISL) FDA Review

Separately, Merck’s doravirine/islatravir (DOR/ISL) — a daily oral two-drug regimen without an integrase inhibitor — has an FDA target action date of April 28, 2026. This broadens the landscape of long-acting-friendly combination options that could be paired with lenacapavir in the future.

Frequently Asked Questions About Lenacapavir

Does lenacapavir cure HIV?

No. Lenacapavir does not cure HIV. For people already living with HIV, it suppresses the virus — keeping viral loads undetectable — but the virus remains in the body. For HIV-negative people, it prevents infection, but it is not a cure or a vaccine.

Can I use lenacapavir if I’ve never taken HIV medicine before?

For treatment, lenacapavir is currently approved only for treatment-experienced individuals with multidrug-resistant HIV. However, clinical studies are evaluating lenacapavir in treatment-naive individuals, and future approvals for first-line treatment are possible. For PrEP, there’s no prior HIV medication requirement — it is for HIV-negative people regardless of treatment history.

How long does lenacapavir stay in my body?

Lenacapavir’s long half-life means it remains at therapeutically active concentrations in the body for months after an injection. However, if you stop injections without transitioning to another effective regimen, levels will eventually fall below therapeutic concentrations. If treatment is discontinued, a fully active oral combination regimen must typically be started within four weeks to prevent resistance development.

What if I need to stop taking lenacapavir?

This is an important safety point. Because lenacapavir lingers in the body, stopping treatment without a plan puts you at risk. If you are HIV-positive and lenacapavir is discontinued, you must start a fully active antiretroviral combination within four weeks to prevent resistance. Speak to your infectious disease specialist before making any changes to your regimen. For guidance on navigating complex health decisions and your rights as a patient, see Ilastia’s health and legal resources.

Can transgender people use lenacapavir?

Yes. Studies confirm there are no significant interactions between lenacapavir and estrogen or testosterone used for gender-affirming hormone therapy. Lenacapavir is an excellent PrEP option for transgender and non-binary individuals, and the PURPOSE 2 trial specifically enrolled gender-diverse participants.

What is the difference between lenacapavir for PrEP and Truvada?

Truvada (emtricitabine/tenofovir disoproxil fumarate) is a daily oral PrEP pill. Lenacapavir (Yeztugo) is an injection given twice a year. Both are highly effective, but lenacapavir requires far fewer clinic visits and eliminates the need for daily medication adherence. Your doctor can help you decide which suits your lifestyle best. You can also explore more health comparisons on Ilastia.

Is lenacapavir safe during pregnancy?

There is limited data on lenacapavir use during pregnancy. The injection form is not currently recommended while pregnant or breastfeeding. If you become pregnant while using lenacapavir, speak with your healthcare provider immediately about your options.

A Wider Perspective: Why Lenacapavir Matters Beyond the Individual

The excitement around lenacapavir extends well beyond any one person’s treatment decision. The WHO estimates that there are still approximately 1.3 million new HIV infections every year globally — a number that daily oral PrEP and existing treatments have failed to bring down to zero, largely because adherence is hard. You have to remember a pill every single day, navigate stigma at every pharmacy visit, and often pay out of pocket in countries without universal healthcare.

Lenacapavir reframes the problem entirely. Two injections a year removes almost all of those barriers. The challenges that remain — particularly insurance coverage, healthcare access, and social stigma around HIV testing — are real but surmountable given the political will and the right public health infrastructure.

There is also the question of health equity. The people most affected by HIV globally are often those with the least access to cutting-edge medicines. The $40-per-year generic access deal — which could reach 120 low- and middle-income countries — represents a genuine attempt to close that gap from the very beginning of a drug’s commercial life. Historically, that has taken a decade or more. If the current partnerships hold, it could happen in under three years for lenacapavir.

For communities in the United States, the picture is similarly complex. CDC data show that Black Americans and Latino Americans are disproportionately affected by HIV — and also face higher rates of PrEP discontinuation due to cost, stigma, and lack of culturally competent healthcare. A twice-yearly injection could address all of those factors simultaneously. Advocates also note that for people experiencing housing instability, substance use disorders, or incarceration, a medication that only requires two clinic visits per year is radically more accessible than a daily pill.

The bottom line is this: lenacapavir is not just a better drug. It could be the infrastructure for finally reaching the WHO‘s goal of ending AIDS as a public health threat. That is a big claim — but the science, for once, is backing it up.

For more on navigating health decisions, understanding your insurance rights when accessing new medications, and staying informed about breakthrough medical advances, explore Ilastia’s full library of health and insurance articles. We also cover related topics including how health insurance works for preventive care, your rights when an insurer denies coverage, and how to access prescription assistance programs.