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The introduction of oral PrEP pills in 2012 was a breakthrough moment for HIV prevention, empowering people to protect themselves by taking a pill once a day.
Over a decade later, it seems that PrEP’s next big step forward is here. Yeztugo® (lenacapavir), a new form of injectable PrEP that requires just two doses per year to protect against HIV, was recently approved by the FDA.
“While an HIV vaccine remains elusive, lenacapavir is the next best thing: a long-acting antiretroviral shown in trials to prevent almost all HIV infections among those at risk."
Dr Tedros Adhanom Ghebreyesus, WHO Director-General (WHO)
While Yeztugo is becoming available to the public for the first time, it’s been making waves in the healthcare community for years. That’s because studies have shown that despite only being taken once every six months, Yeztugo is just as effective at preventing HIV as taking oral PrEP pills every day — and potentially even more so.
What studies say about the effectiveness of Yeztugo®
Yeztugo® was approved by the FDA in June 2025, following a series of large-scale clinical trials known as the PURPOSE studies that began in 2021. These studies looked at how effective Yeztugo® is at preventing HIV compared to oral PrEP across a broad range of people.
In PURPOSE 1, which included 5,338 cisgender women in Uganda and South Africa, zero (0) HIV infections were reported among the 2,134 participants who received Yeztugo®. In comparison, 1.82% of participants who received Descovy® and 1.5% of participants who received Truvada® reported HIV infections in the same period. (NEJM, 2024).
PURPOSE 2 included 3,265 gay, bisexual, and other men who have sex with men, as well as transgender and nonbinary participants, across multiple countries. In this study, just 0.09% of participants receiving Yeztugo® reported HIV infections, compared to 0.82% of participants receiving daily Truvada®. (NEJM, 2024).
At first glance, one might conclude that Yeztugo® is clearly far more effective than daily oral PrEP. But the truth is a little more complicated.
The importance of adherence in PrEP effectiveness
HIV prevention isn’t about just a type of medication or behaviour — it’s a routine of that medication or behaviour. Just like you need to use a condom for it to work, you need to take medication for it to work. Oral PrEP can be 99% effective at preventing HIV when taken exactly as prescribed, but the as prescribed part is crucial. Delayed or missed doses can result in PrEP being less effective, increasing the risk of HIV infection.
Researchers point out that poor adherence to oral PrEP’s dosing schedule is almost certainly the reason that Yeztugo® (lenacapavir) outperformed oral PrEP in the PURPOSE studies:
“In both studies, oral PrEP adherence was suboptimal and decreased over time during the study period. This suggests that lenacapavir’s superior efficacy is likely related to its long-acting injectable properties, allowing it to bypass the challenges of maintaining long term adherence to oral medications.” (NIH, 2025)
Simply put, oral PrEP recipients who must take their medication daily were more likely to miss their doses than Yeztugo® recipients, who require just one injection every six months, administered by a healthcare professional. While the difference in medication itself could play a small role, it’s most likely that how each medication was delivered to patients made the biggest difference in effectiveness.
Is Yeztugo actually more effective than oral PrEP?
The PURPOSE studies suggest that Yeztugo® may have higher real-world effectiveness than oral PrEP at preventing HIV infections, particularly for people who find it difficult to take a pill every day.
People could find taking a daily pill challenging for many reasons. They could require an extreme level of discreteness, find pills uncomfortable to swallow, face challenges accessing timely refills, or simply be forgetful. For these people and others, Yeztugo® could potentially provide a more consistent level of protection against HIV.
Both oral and injectable PrEP can be over 99% effective when taken correctly. What will make the biggest difference in effectiveness for you is choosing the PrEP method that fits best with your lifestyle, your preferences, and your ability to stay on schedule.
“The results [of the PURPOSE studies] not only show that Yeztugo provides strong protection against HIV and was well tolerated in these groups, but also highlight the critical need for PrEP options that reflect people’s preferences — reducing barriers to uptake and helping close persistent gaps in prevention.”
Linda-Gail Bekker, Director of the Desmond Tutu HIV Center, former President of the International AIDS Society (Gilead)
Oral PrEP isn’t going anywhere
While Yeztugo® clearly represents a new breakthrough in HIV prevention, it doesn’t change the fact that oral PrEP is highly effective and readily available today.
Truvada® and Descovy® are both FDA-approved and widely prescribed. When taken consistently, they provide strong protection against HIV.
It could be some time before those who would benefit most from Yeztugo® are able to access it. For most people, oral PrEP is easier to access in terms of insurance coverage, pharmacy supply, and lab requirements — at least for now.
The most effective PrEP is the one that you take
Yeztugo® represents an incredible step forward for HIV prevention, but it doesn’t erase the steps we’ve taken so far. If you believe you’re at risk of HIV and could benefit from PrEP, consider the options available to you both right now and in the future.
Want to talk to an expert? Book a free virtual appointment with a Freddie clinician to discuss your options for PrEP, both injectable and oral.
Yeztugo® is a registered trademark of Gilead Sciences.
