Gilead Targets HIV Prevention Dominance With Twice-Yearly Yeztugo as GSK Mounts a Defense
Gilead Sciences is taking a bold step to further entrench itself as the dominant force in HIV care, this time with its latest innovation in pre-exposure prophylaxis (PrEP). Following the U.S. approval of Yeztugo, a twice-yearly injectable for HIV prevention, analysts are projecting peak sales of up to $4.5 billion for the drug—a potential game-changer in a competitive space still largely led by daily pills and bi-monthly injections.
But standing in Gilead’s way is GSK and its HIV-focused joint venture, ViiV Healthcare, which currently markets the bi-monthly injectable Apretude. The launch of Yeztugo signals not only a shift in patient expectations but also the beginning of a new phase in the battle for control over the fast-growing PrEP market.
Gilead’s HIV Business: Already a Powerhouse
Gilead has long been a dominant player in the HIV treatment and prevention market. In 2024 alone, the company generated $19.6 billion from its HIV portfolio, with the lion’s share—$13.4 billion—coming from Biktarvy, a once-daily triple-combination therapy for people living with HIV. Descovy, another key product used for both treatment and PrEP, added $2.1 billion to Gilead’s bottom line, mostly from prevention use.
Despite this dominance, Gilead is not resting on its laurels. With the approval of Yeztugo, the company is targeting not only new users but also existing PrEP patients currently taking oral therapies like Descovy or injectables like GSK’s Apretude.
Targeting Three Distinct Patient Pools
Speaking at a Goldman Sachs healthcare event in June, Gilead CEO Daniel O’Day identified three core patient groups the company aims to capture with Yeztugo.
1. Current U.S. PrEP Users:
Gilead’s immediate focus is on converting the estimated 400,000 to 450,000 current PrEP users in the U.S. O’Day pointed out that adherence to daily pills remains suboptimal, with real-world compliance hovering around 50%. By offering a more convenient, twice-yearly injectable option, Yeztugo may offer a solution that improves long-term protection.
Feedback from physicians supports this strategy. According to Mizuho analysts, one HIV specialist indicated that the “vast majority” of patients currently using Apretude—and the “majority” on daily oral PrEP—could switch to Yeztugo. Another provider, however, offered a more tempered outlook, estimating that only 30% to 40% of their patients would transition.
Despite differences in expectations, most agree that Yeztugo is poised to reshape the market. Gilead anticipates achieving 70% to 75% payer coverage within six months of launch, and over 90% by the end of the first year—setting the stage for rapid uptake.
2. The Untapped Market:
The second group includes the 750,000 to 800,000 individuals in the U.S. who are at risk for HIV but are not currently on PrEP. Many of these potential users come from communities underserved by current HIV prevention programs.
According to O’Day, most current PrEP users are men who have sex with men and reside in major metropolitan areas. Gilead aims to increase outreach and awareness among other vulnerable groups, such as people of color and those in rural regions. Physicians are already seeing interest from patients who have never previously taken PrEP but are inquiring about Yeztugo.
3. Global Expansion:
While PrEP is predominantly a U.S.-centered market today, Gilead sees a significant long-term opportunity internationally. O’Day noted that each HIV infection prevented in the U.S. could save $1.1 million in lifetime healthcare costs, making Yeztugo an attractive option for health systems around the world. The company plans to engage with global health ministries to bring Yeztugo to underserved populations in other regions.
GSK Responds With Caution and Optimism
Yeztugo’s anticipated success could disrupt one of GSK’s key growth products: Apretude. In 2024, Apretude sales surged nearly 90% to £279 million ($383 million), making it a significant asset in ViiV Healthcare’s portfolio.
Still, GSK isn’t ready to concede. David Redfern, chairman of ViiV, expressed confidence in Apretude’s future during a February earnings call. He argued that the PrEP market remains underpenetrated and that a new long-acting option could expand the overall pie rather than shrink Apretude’s share.
Redfern also pointed to potential drawbacks with Yeztugo, including a reported frequency of nodules forming at the injection site in the abdomen. For image-conscious users, this could be a deterrent.
“We now know that there’s quite a high frequency of nodules that people experience… For potential PrEP users who are body image conscious… that potentially is an issue,” he said.
GSK’s Pipeline Aims to Reclaim Ground
Even as Gilead surges ahead, GSK is actively building its arsenal. The company is advancing several HIV candidates designed to challenge Biktarvy and Yeztugo, including VH184, a promising integrase inhibitor with strong resistance data, and N6LS, a broadly neutralizing antibody. GSK is also developing VH499, a capsid inhibitor, and is targeting the launch of its own twice-yearly HIV treatment and PrEP injectable between 2028 and 2030.
The goal is clear: retain relevance in a market that Gilead continues to dominate. While Gilead currently holds a 51% share of the U.S. HIV treatment market, GSK is betting that long-acting injectables will become the new standard of care—offering convenience, better adherence, and more effective public health outcomes.
The Battle Ahead
As Yeztugo begins its commercial rollout, the dynamics of the HIV prevention market are shifting quickly. Gilead is banking on convenience, payer coverage, and patient interest to drive adoption. Meanwhile, GSK is preparing to defend its stake with an evolving pipeline and a belief that competition will expand the overall market.
One thing is certain: in the rapidly evolving field of HIV prevention, long-acting injectables are no longer the future—they’re the present. And Gilead, with Yeztugo, may have just fired the opening shot in a new era of competition.
