Gilead Faces Long-Term HIV Threat as Merck's Rival Drug Succeeds in Trial
Merck's two-drug regimen proves as effective as Gilead's blockbuster Biktarvy, signaling a significant competitive shift in the multi-billion-dollar HIV market post-2026.
Gilead Sciences is facing the most significant competitive challenge to its multi-billion-dollar HIV franchise in years after rival Merck announced positive data from a late-stage trial for a new treatment. The study showed Merck’s two-drug combination was as effective as Gilead’s blockbuster, Biktarvy, the current market leader.
In a pivotal Phase 3 study, Merck’s investigational once-daily tablet, a combination of doravirine and islatravir (DOR/ISL), demonstrated non-inferiority to Biktarvy in suppressing the HIV-1 virus in treatment-naïve adults. The company announced the positive topline results on Tuesday, signaling its intent to enter a market that Gilead has long dominated.
While the immediate market reaction was muted—Gilead shares (NASDAQ: GILD) slipped a modest 0.4% to $126.71 in midday trading—the development creates a formidable long-term threat to Gilead’s most critical revenue stream. Biktarvy is a cornerstone of Gilead's portfolio, generating over $3 billion in sales in the third quarter of 2025 alone and commanding a majority of the U.S. market share for HIV treatments.
Merck's entry could disrupt that dominance by offering physicians and patients a different treatment profile. Biktarvy is a three-drug cocktail based on an integrase inhibitor (INSTI). In contrast, Merck’s two-drug regimen is a non-INSTI based option. This is a key differentiator, as some INSTI-based regimens have been associated with side effects such as weight gain and potential cardiometabolic issues, a growing concern in long-term HIV care.
“This is a clear strategic victory for Merck and a long-term headache for Gilead,” said a biotech analyst at a major investment bank. “While Biktarvy's position is secure for the next couple of years, the narrative from 2026 onwards is now officially complicated. Merck is offering a potent, simplified regimen with a potentially differentiated safety profile.”
The U.S. Food and Drug Administration (FDA) has already accepted a New Drug Application (NDA) for Merck’s combination therapy, with a target action date of April 28, 2026. This sets a clear timeline for the competitive showdown.
For Gilead, the challenge comes as the company works to diversify its own pipeline beyond its established HIV portfolio. The company has invested heavily in oncology and is advancing its own next-generation HIV treatments, including the long-acting injectable lenacapavir, marketed as Sunlenca. This injectable, administered twice-yearly, represents Gilead's strategic pivot to fend off oral-tablet competitors by changing the treatment paradigm altogether.
The durability of Gilead's HIV sales has been a key factor in its financial performance, with the franchise consistently beating analyst expectations. With a market capitalization of over $157 billion, the company's valuation is heavily reliant on the continued success of drugs like Biktarvy. According to company filings, the HIV product segment accounts for the vast majority of its product sales.
Investors will now be closely watching for further data from Merck, particularly around the long-term safety and metabolic profiles of its drug. Any data suggesting a clear advantage in reducing side effects could accelerate market share erosion from Biktarvy upon launch.
While the threat is not immediate, the successful trial marks the beginning of a new chapter in the HIV treatment landscape. Gilead's fortress, once considered nearly impenetrable, now has a credible challenger on the horizon, forcing the company to innovate aggressively to protect its market-leading position.