Pritelivir Offers Breakthrough for HIV Patients with Refractory Herpes

DENVER, CO – February 25, 2026 – A novel oral antiviral drug has demonstrated significant success in treating severe and stubborn herpes simplex virus (HSV) infections in people living with HIV, a population often left with few effective options. In a late-breaking presentation at the Conference on Retroviruses and Opportunistic Infections (CROI), German pharmaceutical company AiCuris Anti-infective Cures AG revealed compelling data from its pivotal Phase 3 trial.

The results from a subgroup analysis of the PRIOH-1 study showed that pritelivir achieved complete healing of painful HSV lesions in 61% of treated HIV patients, a stark contrast to the 20% healing rate observed in those receiving current standard therapies. This statistically significant finding represents a potential paradigm shift for managing one of the most common and challenging opportunistic infections in immunocompromised individuals.

The Challenge of Resistant Herpes in HIV

For people living with HIV, a weakened immune system turns common viral infections into severe medical challenges. HSV, which causes lifelong infections manifesting as oral or genital sores, can become particularly aggressive. In this population, HSV outbreaks are often more frequent, prolonged, and can lead to atypical, painful lesions that resist standard treatment. This condition, known as refractory HSV, poses a significant clinical burden.

Furthermore, co-infection with HSV-2 can increase the risk of HIV acquisition and may even accelerate the progression of HIV itself. The repeated use of first-line antivirals like acyclovir to manage these outbreaks has led to a rise in drug-resistant HSV strains, leaving clinicians with limited and often highly toxic alternatives.

“Patients living with HIV who develop refractory HSV infections with or without acyclovir resistance often present with prolonged, atypical, and clinically challenging disease courses,” said Professor Jean-Michel Molina of the University of Paris Cité, a principal investigator who presented the findings at CROI. “The subgroup analysis from this Phase 3 trial provides important evidence that pritelivir can achieve meaningful lesion healing in this population, using an oral treatment option.”

Current second-line treatments for resistant HSV, such as intravenous foscarnet or cidofovir, carry a heavy price. They often require hospitalization for administration and are associated with severe side effects, most notably kidney damage and electrolyte imbalances, complicating care for an already vulnerable patient group.

A Novel Mechanism to Overcome Resistance

Pritelivir stands apart from decades of antiviral development due to its unique mechanism of action. Unlike traditional nucleoside analogues such as acyclovir, which target the viral DNA polymerase enzyme and require activation by a viral enzyme, pritelivir is a helicase-primase inhibitor. It works by directly blocking the helicase-primase complex, a viral machinery essential for unwinding the viral DNA and initiating its replication.

This novel approach means pritelivir’s effectiveness is not dependent on the viral enzymes that are often mutated in resistant strains. Consequently, it remains active against HSV that has developed resistance to both acyclovir and foscarnet, directly addressing the core of the treatment challenge.

“People living with HIV often experience more complex clinical manifestations of HSV, which can make infections particularly difficult to treat,” said Cynthia Wat, CMO of AiCuris. “As an antiviral with a novel mechanism of action, pritelivir has shown efficacy in the treatment of refractory HSV infections with or without resistance and may offer an important option for people living with HIV facing severe, refractory HSV disease.”

The convenience of an oral, once-daily pill further distinguishes pritelivir from the burdensome intravenous alternatives, offering the potential for outpatient treatment and significantly improving quality of life.

A Closer Look at the Trial Data

The PRIOH-1 study is a global, comparative trial that enrolled immunocompromised patients from various groups, including those with HIV, transplant recipients, and individuals with malignancies. The subgroup analysis presented at CROI focused on the 38 participants living with HIV, who constituted nearly 38% of the trial's randomized cohort.

Within this subgroup, the majority (81.6%) had refractory HSV, meaning their lesions had not improved after at least seven days of standard antiviral therapy, while 18.4% had laboratory-confirmed resistance to acyclovir. These patients, with a mean CD4 cell count of 334.8 cells/mm³, represent a clinically complex population.

The results were striking. After up to 28 days of treatment, 61% of patients receiving oral pritelivir (14 out of 23) achieved complete lesion healing. In contrast, only 20% of patients receiving investigator’s choice therapy (ICT), which included IV foscarnet, IV/topical cidofovir, or topical imiquimod, saw their lesions heal completely. This represents a 37% adjusted treatment difference in favor of pritelivir.

The safety profile also strongly supported pritelivir. Treatment discontinuations due to drug-related adverse events were ten times lower in the pritelivir group (2.0%) compared to the ICT group (20.0%). The most common side effects associated with pritelivir were generally mild to moderate, including headache, diarrhea, and nausea, a favorable profile when compared to the known renal toxicities of the intravenous options.

A New Standard of Care on the Horizon

With these robust Phase 3 results and a previously granted Breakthrough Therapy designation from the U.S. Food and Drug Administration (FDA), pritelivir is on a clear path toward regulatory approval. AiCuris has announced its intention to submit a New Drug Application (NDA) to the FDA in 2026, potentially making the drug available to patients in the near future.

The success of pritelivir strengthens AiCuris's strategic focus on developing targeted anti-infective therapies for immunocompromised individuals. The company has already found success with PREVYMIS®, a drug for preventing cytomegalovirus in transplant recipients marketed by its partner MSD. The promising data for pritelivir positions it as the company’s next major asset, poised to address a market with no significant therapeutic innovation in over two decades.

Infectious disease experts not involved in the study have expressed optimism, noting that a safe, effective, and orally administered treatment for refractory HSV could be life-changing for patients who currently endure debilitating symptoms and toxic therapies. For people living with HIV who have battled painful and persistent herpes infections, the arrival of pritelivir signals a long-awaited and much-needed advancement in their care.