Twice-Yearly Triumph: How Gilead's Revolutionary Shot is Poised to End the HIV Epidemic
The global fight against Human Immunodeficiency Virus (HIV) has reached a critical juncture, marked by the recent European Union (EU) approval of Gilead’s groundbreaking drug, Yeytuo (lenacapavir). This long-acting injectable drug for HIV prevention has been heralded by analysts and charitable organizations as a key tool for curbing new infection rates. The approval of Yeytuo consolidates the drug’s potential to become one of Gilead’s foremost products in the future, transitioning the landscape of HIV prevention from often-forgotten daily pills to a highly convenient, twice-yearly shot.
Understanding the Mechanism: Yeytuo's Role as PrEP
Yeytuo is specifically approved as a pre-exposure prophylaxis (PrEP) option. PrEP is a prevention method designed to reduce the risk of acquiring HIV infection. Specifically, Yeytuo is indicated for use in adults and adolescents who are at an increased risk of sexually acquiring HIV-1 and who weigh at least 35 kilograms (kg).
The fundamental science behind Yeytuo’s protective capability involves its method of action within the human body. As a long-acting antiretroviral agent, the drug works by interfering with multiple steps in the complex viral lifecycle of HIV. By disrupting these crucial stages, Yeytuo effectively inhibits the replication of the HIV-1 virus, thereby preventing infection.
The recent European marketing authorization for Yeytuo stems from an approval granted by the European Commission (EC). This pivotal decision followed a positive recommendation issued just the month prior by the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP). Notably, Gilead proceeded along an accelerated regulatory pathway for this drug, a status that grants Yeytuo an additional year of protection on the market.
The EU approval closely follows a similar momentous decision made in the United States. In June 2024, the US Food and Drug Administration (FDA) approved the injectable drug, where it is marketed under the brand name Yeztugo. Analysts at GlobalData hailed the US approval of Yeztugo as a ‘momentous step’ for HIV prevention, a sentiment that is equally applicable to the approval of Yeytuo in Europe. The European region alone recorded approximately 24,700 new HIV diagnoses in 2023, underscoring the urgent need for more effective and accessible prevention methods. The Elton John AIDS Foundation echoed the excitement surrounding this advancement, labeling Yeytuo a “breakthrough prevention method that will fundamentally bend the curve of new HIV infections”.
The Power of Convenience: Efficacy Meets Adherence
Perhaps the most revolutionary aspect of Yeytuo is its dosing schedule: it is administered as a subcutaneous injection twice yearly. This semi-annual requirement stands in stark contrast to the standard of care that currently dominates the PrEP landscape. Currently, most available PrEP therapies require patients to take a daily pill orally. While effective when taken correctly, this daily regimen often results in a significant drawback: poor adherence. When patients struggle to adhere to a daily oral medication schedule, the protective efficacy of the drug is compromised, leaving them vulnerable to infection.
Lenacapavir, the active ingredient in Yeytuo, is designed to overcome this obstacle. As a long-acting antiretroviral agent, a single injection provides continuous protection against HIV infection for six months. This immense increase in convenience—moving from 365 doses a year to just two—is crucial for maximizing uptake and effectiveness across patient populations.
Experts believe this novel schedule could be the key to turning the tide against the epidemic. Jean-Michel Molina, a professor of infectious diseases at Université Paris Cité, stated that Yeytuo’s novel twice-yearly dosing schedule combined with its high efficacy "could be the transformative HIV prevention option in Europe we’ve been waiting for" to significantly reduce new infections and achieve real progress toward ending the HIV epidemic.
The clinical evidence supporting Yeytuo’s potential is compelling. The high efficacy demonstrated in trials is staggering. Two major clinical trials, PURPOSE 1 (NCT04994509) and PURPOSE 2 (NCT04925752), studied the efficacy of the twice-yearly subcutaneous lenacapavir injection. The PURPOSE 1 trial achieved a 100% success rate in preventing HIV infection among participants. Similarly impressive, the drug prevented infections in 99.9% of the participants enrolled in the PURPOSE 2 trial. Collectively, these two studies involved a total of 4,313 participants, providing a robust foundation for the claims of high efficacy.
Beyond the European and US regulatory bodies, the drug has received powerful backing from global health organizations. Earlier this year, the World Health Organization (WHO) endorsed the use of injectable lenacapavir in the fight against HIV. The WHO specifically cited the drug’s high efficacy and its long-acting nature as reasons for its support. Dr. Tedros Adhanom Ghebreyesus, the WHO Director General, summarized the drug’s importance by describing the shot as the “next best thing” after a successful HIV vaccine, emphasizing that a vaccine remains elusive in the pharmaceutical world so far.
The Financial Forecast and the Challenge of Cost
The approval of Yeytuo not only carries significant public health implications but also substantial financial potential for Gilead. GlobalData’s Pharma Intelligence Centre has forecasted that global sales of lenacapavir are expected to reach $3.3 billion by 2031. Based on these projections, the drug is anticipated to enter the highly lucrative category of blockbuster status by the year 2027. While this forecast demonstrates strong potential, it is important to contextualize lenacapavir within Gilead’s existing portfolio. Currently, Gilead’s highest-selling drug is the HIV antiviral Biktarvy, which generated global sales totaling $13.4 billion in 2024.
Despite the promising efficacy and market potential, a significant obstacle to the widespread global uptake of Yeytuo (or Yeztugo in the US) is its potential cost. Pricing is often a barrier that limits access to life-saving medications. The US list price for Yeztugo is substantial, currently sitting at $28,218 per year for each patient. This price point can be compared to the only other injectable PrEP therapy available in the US, GSK’s Apretude, which costs $22,000 per year, though Apretude requires monthly administration rather than the twice-yearly schedule of Yeztugo. As of the time of the source information, Gilead had not disclosed any discussions regarding reimbursement strategies or specific drug pricing within the member states of the European Union.
Expanding Global Access: A Worldwide Prevention Strategy
Gilead recognizes the immense global need for advanced prevention methods, particularly in regions most affected by the HIV burden. Beyond the EU and US approvals, the company has initiated extensive regulatory efforts across the globe. Gilead has filed for regulatory review of the twice-yearly lenacapavir for PrEP with authorities in several key international regions, including Australia, Brazil, Canada, South Africa, and Switzerland. Furthermore, the company has future plans to pursue regulatory action in additional nations, specifically naming Argentina, Mexico, and Peru.
A crucial component of Gilead’s strategy is focusing on areas where the need for preventative measures is most acute: low- and middle-income countries (LMICs). The company has stated its intent to pursue accelerated reviews with regulatory authorities in these countries. This strategy includes priority registrations covering 18 nations that collectively represent 70% of the HIV burden among the 120 countries included in Gilead’s voluntary licensing agreements.
To ensure that the medication reaches those who need it most, Gilead has established a critical partnership with the Global Fund to Fight AIDS, Tuberculosis and Malaria. This collaboration is specifically designed to supply lenacapavir. Under the terms of this partnership, Gilead aims to supply the drug for up to two million people in low-income countries over a three-year period.
In conclusion, the European approval of Gilead’s Yeytuo marks a true turning point in HIV prevention. By providing an exceptionally highly effective drug that demands adherence only twice per year, Yeytuo addresses the primary failings of existing daily PrEP therapies. Backed by powerful clinical data and endorsed by major health organizations like the WHO, this injection has earned its designation as a breakthrough prevention method. While financial barriers pose a real challenge to global equitable access, Gilead's strategic efforts in LMICs and its partnership with the Global Fund suggest a commitment toward realizing the drug’s potential to dramatically reduce new infections worldwide and make genuine progress toward ending the HIV epidemic for good.
HIV Researchers:
Lisette M. Johnson, ScD was listed in a 2014 research article, "Recruiting Minority Men Who Have Sex With Men for HIV Research," as being with the Bloomberg School of Public Health at Johns Hopkins University in Baltimore.
John B. Hylton, PhD, was also listed as a Johns Hopkins researcher at the Bloomberg School of Public Health on the same 2014 article.
Jean-Jacques Kayembe, MD, MPH, PhD candidate, is the Founder and Executive Director of the Congolese Health Board, a nonprofit organization that serves the Congolese community in the state of Washington and provides HIV education. He has served as a program manager at Public Health Seattle and King County, supporting COVID-19 surveillance and prevention activities in communities of color. He is pursuing his PhD in epidemiology at Walden University and trained as a physician at the University of Kinshasa in the Democratic Republic of Congo.
