Vaccines are often the best tool to curb the spread of a virus. But the lengthy quest to stop HIV has proven much more complicated.
Without a viable vaccine, drug developers have given rise to a range of antiretroviral and pre-exposure prophylaxis medications in the last few decades. These options have bent the arc of disease progression away from a high likelihood of death and made HIV a manageable, long-term illness. A silver bullet cure or vaccine, however, has remained elusive.
Yet one of the best weapons so far against HIV is now entering the scene.
Gilead Sciences won FDA approval last year for a PrEP medication with the potential to “end HIV,” according to the company’s chief commercial and corporate affairs officer, Johanna Mercier.
The rollout comes after Gilead achieved landmark results in the clinic. The phase 3 trial tested the long-lasting version of its PrEP medication lenacapavir in preventing new infections among thousands of participants and boasted 100% efficacy in cisgender women.
“It gave us all goosebumps,” Mercier said, describing the experience of learning the trial results. “But then it became: Let’s get into action.”
Although other PrEP medications have been approved as daily pills or bi-monthly injections, the new formulation only needs to be administered twice a year — dramatically lowering a major access burden for patients.
Now marketed as Yeztugo, the medication has racked up approvals in 50 other countries, according to Mercier. While Yeztugo marked a milestone achievement in drug R&D, the work of getting it to patients is just beginning.
Gilead is now tasked with delivering needed doses in a global treatment landscape that’s been rocked by funding cuts and is still mired in lingering cultural stigmas. To pull it off, Gilead is relying on a vast network of international partners, its historical know-how in HIV and lessons learned from past pharma stumbles in the space.
Hitting the ground running
Within weeks of Yeztugo succeeding in the clinic, Gilead began laying the groundwork for a large-scale global rollout, announcing a royalty-free voluntary licensing agreement with six generic manufacturers to supply the medication in 120 low- and middle-income countries.
“Even before FDA submission, we got to work early to ensure we could get into areas like sub-Saharan African countries within the same year,” Mercier said.
An estimated 1.3 million people around the world were infected with HIV in 2024, according to UNAIDS.
Gilead’s manufacturing deals are part of a broader goal to deliver enough doses for up to 2 million people over the next three years at no profit to the company. The far-reaching effort is pulling together multiple partners including The Global Fund, a major player in the global infectious disease arena, the Gates Foundation, the Clinton Health Access Initiative and more.
Although Gilead is “essential” in creating access to Yeztugo, the complexity of its rollout will require a broad array of stakeholders, including local governments and regulators, to do their part, according to Mitchell Warren, executive director of AVAC, a nonprofit that operates like “air traffic control” to help donors and program implementers deliver HIV prevention options.
Previous global rollouts of this magnitude haven’t always gone well.
“In the past 15 years, we have seen the field squander every opportunity with PrEP medications,” Warren said.
After the 2021 approval of Apretude, a six-times yearly injectable PrEP medication by GSK’s ViiV Healthcare, rollout was hampered by years of negotiations around pricing and manufacturing, Warren explained. With Yeztugo, Gilead is moving much more swiftly to lock production plans into place while addressing cost concerns.
“In the 18 months since we knew Yeztugo was safe and effective, we’ve seen every milestone delivered at a far faster clip than with anything else,” Warren said.
Meanwhile in the U.S., Gilead has won coverage for Yeztugo with about 85% of payers and secured a “zero copay” for 90% of the plans, Mercier said. The company also launched a program for uninsured Americans to receive free access to Yeztugo, which carries a list price over $28,000 per year.
Although some analysts have pegged Yeztugo to eventually hit blockbuster status, Gilead is targeting $800 million in sales this year.
To keep Yeztugo doses flowing to new patients, plenty of barriers remain.
Along came Trump
International aid has long been at the heart of the global HIV response — funding 80% of prevention programs in low- and middle-income countries, according to the United Nations. But sudden and steep funding cuts triggered by the Trump administration last year contributed to a 30% to 40% drop in international assistance for HIV programs in 2025.
The financial clawback could threaten global access to Yeztugo, which hinges on a carefully crafted network of patient services.
“Periods of uncertainty or reductions in external funding can affect prevention programs quickly because PrEP access depends not only on medicines but also on the clinics, community outreach, testing services and health workers that support delivery,” Ravini Senanayake, public relations manager at The Global Fund, said in an email.
Despite the now “challenging financing environment,” organizations like The Global Fund are working with various governments and partners to “help protect continuity of prevention and treatment services,” Senanayake said.
“There’s a cruel irony right now. One of our greatest opportunities is coming at one of the most politically difficult times.”
Mitchell Warren
Executive director, AVAC
Some revenue streams that were shut down have since been partially restored, such as the U.S.’ PEPFAR program, which “accounts for more than 90% of PrEP initiations globally,” according to the program. But it remains to be seen if the moves by various organizations to fill the HIV treatment gaps will be enough for Gilead to hit its access goal.
“There’s a cruel irony right now,” Warren said. “One of our greatest opportunities is coming at one of the most politically difficult times … so we are starting with both hands tied behind our backs.”
It’s particularly unclear if the health ministries in various countries will have the budget to buy doses of Yeztugo for their citizens, Warren said.
“Right now, they are struggling with paying for treatments to keep people alive, so they’re not prioritizing prevention,” he said. “So there are huge question marks around if we can see that great science translated to public health impact.”
South Africa is particularly vulnerable to political and financial roadblocks.
Although South Africa is home to the highest number of people living with HIV, the country has been specifically targeted by the U.S. government for funding cuts. After a temporary pause in PEPFAR funding last year caused 12 specialized HIV clinics to close and triggered thousands of layoffs, according to the Associated Press, a bridge plan was put in place to restore aid. But that plan is set to expire at the end of this month.
Gilead, which has gotten flak for not including a generic producer in South Africa in its manufacturing agreements, is now in negotiations for a voluntary license to manufacture generic versions of Yeztugo in the country.
“Gilead is supportive of working with the South African National AIDS Council, which will issue a request for proposals for generic manufacturing in South Africa,” the company said in an emailed statement, adding that it will review proposals and “assess whether required quality standards can be met before any voluntary license is granted.”
There’s also still a “big gap” in Gilead’s licensing agreements because they leave out countries in Latin America and Asia, Warren said.
And even if supply goals are met, the effort to make a dent in HIV infections is also tied to patient adherence.
In some of the programs already administering monthly PrEP injections, only 70% to 75% of patients return on schedule for needed doses — a rate that is “not nearly as good” as in clinical trials, Warren said. Although Yeztugo only needs to be taken twice a year, monitoring will be crucial to ensure access programs help patients attain the medication on time.
“I don’t want to find out in [a few years] that the clinical results were great, but we didn’t see a public health impact,” Warren said. “Its success is in the treatment programs.”
Will Yeztugo end HIV?
Despite the various hurdles, Warren is optimistic Gilead will hit its goal of reaching 2 million patients. Although generic versions of Yeztugo won’t be available until 2027, Gilead said it’s providing the medication at no cost through PEPFAR and The Global Fund in the meantime.
But HIV is still evolving and spreading into new patient populations around the globe. Because of the complexity involved in reaching patients, fully eradicating HIV will likely take more than just one drug, Warren said.
“We still need R&D for additional options,” Warren said. “Yeztugo can’t do it on its own.”
The story of HIV’s ultimate demise could still be written by a vaccine.
A phase 1 trial testing a new mRNA vaccine candidate is slated to start this year, according to the Gavi, an international vaccine nonprofit. The study will contribute to a growing body of research testing if mRNA can overcome the historic scientific hurdles of developing an HIV vaccine.
ViiV also remains active in the HIV drug development space and has four treatments and preventative medicines in its clinical pipeline. Gilead meanwhile has several drug combinations in the clinic it’s developing with the ultimate goal of delivering a cure.
In its ongoing efforts to keep “out-innovating” itself, Mercier is hopeful that with PrEP or other treatments, Gilead will play a leading role in stopping the virus.
“I would love to see it in my generation,” she said. “That would be a huge accomplishment. But I’m also realistic that we’re on a journey.”
