Yeztugo vs Apretude: Which Injectable PrEP Is Right for You?

The injectable PrEP landscape in 2026

Injectable PrEP changed HIV prevention by removing daily pill adherence as a barrier. For people who struggle with daily medications — whether due to memory, substance use, mental health conditions, or just the exhaustion of daily routines — injectable PrEP closes the adherence gap that has limited oral PrEP's real-world effectiveness.

As of 2026, two injectable options exist in the U.S.:

• Apretude (cabotegravir), FDA-approved December 2021, manufactured by ViiV Healthcare. Intramuscular injection every 2 months.
• Yeztugo (lenacapavir), FDA-approved June 2025, manufactured by Gilead Sciences. Subcutaneous injection every 6 months.

A once-yearly lenacapavir formulation is in Phase III trials (expected results around 2028). For now, these two are the choices.

Yeztugo vs Apretude: side-by-side comparison

	Yeztugo (lenacapavir)	Apretude (cabotegravir)
FDA approval date	June 18, 2025	December 20, 2021
Manufacturer	Gilead Sciences	ViiV Healthcare
Mechanism	Capsid inhibitor	Integrase strand transfer inhibitor
Dosing schedule	Every 6 months (2x/year)	Every 2 months (6x/year)
Injection type	Subcutaneous (under skin)	Intramuscular (into muscle)
Loading phase	Oral pills during transition	Optional oral lead-in or direct injection
Efficacy vs oral PrEP	96–100% (PURPOSE trials)	89% (HPTN 083)
List price	$28,218/year	~$24,228/year
Typical out-of-pocket cost	$0 w/ assistance	$0 w/ assistance
Medicare coverage	Part B (Oct 2025)	Part B (established)
Medicaid coverage	Rolling out state-by-state	All 50 states
Approved populations	All at-risk adults (weight 35kg+)	All at-risk adults (weight 35kg+)

Dosing: the biggest difference

This is the most practically important difference between the two drugs. Yeztugo requires 2 injections per year. Apretude requires 6.

For someone who values minimizing healthcare appointments, transportation, or the psychological burden of managing a prevention routine, Yeztugo's dosing is transformative. Two visits a year is genuinely low-maintenance healthcare.

For someone who already has regular healthcare visits (quarterly STI screening, routine primary care, etc.), Apretude's every-2-month schedule may naturally align with other appointments.

What the injection experience is actually like

Yeztugo is a subcutaneous injection — typically given in the abdomen, similar to how some diabetes or fertility medications are administered. Subcutaneous injections involve a shorter, thinner needle than intramuscular injections. Most patients describe the Yeztugo injection as mildly uncomfortable but not painful, with minimal soreness afterward.

Apretude is an intramuscular injection given in the buttocks (gluteal muscle). The needle is longer and the injection delivers a larger volume of medication. Many patients describe some post-injection soreness for 1–3 days, often resembling the feeling after a vaccination. The soreness is usually tolerable but more noticeable than after Yeztugo.

Efficacy: both work, with some nuance

Both drugs are highly effective at preventing HIV when properly administered on schedule.

Apretude's HPTN 083 and HPTN 084 trials compared it to daily oral PrEP (TDF/FTC). In HPTN 083 (cisgender men and transgender women who have sex with men), Apretude reduced HIV acquisition by 89% compared to oral PrEP. In HPTN 084 (cisgender women in sub-Saharan Africa), Apretude reduced HIV acquisition by 88% compared to oral PrEP. Both results were statistically significant. Note: the comparator was oral PrEP, not placebo.

Yeztugo's PURPOSE trials showed extraordinary efficacy. In PURPOSE 1 (cisgender women in sub-Saharan Africa), zero participants acquired HIV — a 100% risk reduction. In PURPOSE 2 (a diverse population including cisgender men and transgender people), only 2 participants acquired HIV out of 2,180, a 96% risk reduction. Both results substantially outperformed daily oral PrEP.

Direct head-to-head trials between Yeztugo and Apretude have not been conducted. Both are extremely effective. For the average patient, the efficacy difference is unlikely to be clinically meaningful — the practical differences are in dosing, cost access, and side effects.

Side effects and tolerability

Yeztugo common side effects

• Injection site reactions (nodules under the skin, redness, pain) — most common
• Headache, nausea (less common)
• No significant drug interactions identified to date

Injection site nodules are the most commonly reported Yeztugo side effect — small, firm bumps under the skin at the injection site that can persist for weeks. Most patients consider these manageable but they're worth knowing about.

Apretude common side effects

• Injection site reactions (pain, soreness, redness) — most common, typically 1–3 days
• Headache, fever, fatigue (less common)
• Rare: liver enzyme elevations

Apretude's injection site soreness is more common and more uncomfortable than Yeztugo's, but typically resolves within a few days. Some patients develop temporary nodules at the injection site.

Cost: both are $0 for most patients

On list price, Yeztugo is the more expensive drug ($28,218/year vs ~$24,228/year for Apretude). But for most patients, this difference is irrelevant because patient assistance and insurance coverage bring both to $0 out of pocket.

With commercial insurance

• Yeztugo: Gilead copay savings program covers up to $8,000/year + $100/injection visit
• Apretude: ViiV APRETUDE Savings Program covers up to ~$7,500/year

Without insurance (under 500% FPL)

• Yeztugo: Gilead Advancing Access Medication Assistance Program — free drug, no SSN required
• Apretude: ViiVConnect Patient Assistance Program — free drug, no SSN required

With Medicaid

• Yeztugo: Covered under ACA preventive services mandate ($0); coverage rolling out state-by-state post-October 2025 J-codes
• Apretude: Covered in all 50 states, typically $0

Which one should you choose?

Yeztugo is probably right for you if:

• You value minimizing healthcare visits — two a year is a major life improvement for some people
• You have commercial insurance (Yeztugo's manufacturer program is slightly more generous)
• You're particularly sensitive to the post-injection soreness of intramuscular injections
• You're already a Gilead Advancing Access enrollee for oral PrEP (consolidating through one manufacturer can simplify paperwork)

Apretude might be right for you if:

• Your state Medicaid hasn't yet fully rolled out Yeztugo coverage
• You have existing quarterly healthcare appointments — the every-2-month dosing may naturally align
• Your insurance has Apretude on a preferred tier but Yeztugo requires a difficult prior authorization
• You prefer a drug with longer real-world post-marketing data (Apretude has been in use since 2021; Yeztugo since mid-2025)
• You have a known capsid inhibitor sensitivity (unusual but clinically relevant)

For most newly starting patients

If both are available and affordable for you, Yeztugo's dosing convenience is a significant real-world advantage. Two injections a year vs six is the difference between PrEP as a minor annual healthcare touchpoint and PrEP as an ongoing bi-monthly routine.

That said, Apretude has been prescribed to tens of thousands of patients over four years with a strong safety record and well-established insurance coverage patterns. For patients whose insurance makes Apretude easier to access, it's still an excellent choice.

Frequently asked questions