Pritelivir active against drug resistant herpes in phase 3 study
9 March 2026. Related: Early access, Conference reports, Coinfections and complications, CROI 33 (Retrovirus) 2026.
Simon Collins, HIV i-Base
Drug resistance to HSV-1/2 and refractory herpes outbreaks is a painful and difficult condition. Developing effective and tolerable options remains a high unmet need and particularly affects people who are immunocompromised, including people living with HIV.
CROI 2026 included phase 3 results using the investigational direct-acting antiviral compound pritelivir, presented in an oral presentation by Jean-Michel Molina from Hôpitaux de Paris. Pritelivir is bioavailable with a long half-life (60 hours), enabling once-daily oral dosing and is sensitive to HSV with drug resistance to acyclovir and foscarnet.
The open-label PRIOH-1 study randomised (1:1) 101 people with refractory or drug-resistant HSV-1/2 to either daily oral pritelivir or investigational chosen standard of care (foscarnet IV, cidofovir IV or topical imiquimod) for 28 days (or extended to 42 days) with further 28-day follow-up. Pritelivir used an initial 400 mg loading dose on day 1, with subsequent 100 mg daily dosing.
The primary endpoint was complete lesion healing at day 28.
The sample size was based on expected 85% efficacy with pritelivir and 60% with foscarnet.
Underlying immunocompromised status often included multiple causes and was related to HIV in 38%, cancer in 75%, stem cell transplant in 40%, autoimmune disease in 29% and solid organ transplant in 4%.
Characteristics of the HIV subgroup (n=38) included mean age 48, 76% men, 50% Black with mean CD4 of 330 cells/mm3 (IQR: 143 to 514). All were on ART but viral load results were not given.
With the HIV subgroup, 23 were randomised to pritelivir and 15 to SoC and there were 1 vs 6 discontinuations, respectively, mainly due to poor tolerability or non-response.
Results at day 28 in the overall study and HIV subgroup were 63% vs 28% (p=0.004) and 67% vs 21% (p=0.027), respectively, both showing pritelivir to have significantly superior efficacy.
Benefits were reported irrespective of baseline resistance to acyclovir, although small numbers didn’t reach statistical significance.
Overall, of the nine participants who failed in the pritelivir arm, drug resistance results at failure were only available for 2/9, one of whom showed pritelivir-associated new mutation detected at day 36.
comment
Pritelivir is being developed by German manufacturer AiCuris Anti-infective Cures and top-level results from the PRIOH-1 trial were released in October 2025, reporting continued efficacy in the 42-day analysis (p=0.0001). [2]
The US FDA has designated pritelivir for a breakthrough indication, with submission of a New Drug Indication expected by 1Q 2026.
Longer-term data presented at future meetings will include some cases of lesion recurrence after discontinuation of pritelivir, indicating longer treatment might be needed for some people.
Tolerability was reported as being good (some headache and nausea) with only one early discontinuation but few details were included.
The main drug interactions involve needing to separate dosing of proton pump inhibitors by at least two hours. [3]
An expanded access program (EAP) is available to provide pritelivir to people with treatment resistant HSV-1/2 who are immunocompromised, can’t participate in a clinical trial and have no approved treatment options. [4]
References
- Molina JM et al. Pritelivir for Refractory HSV Infections in Immunocompromised Patients: Results of a Phase III Trial. CROI 2026, Denver. Oral abstract 196.
- Phase 3 trial confirms superior efficacy of oral pritelivir for refractory HSV in immunocompromised patients. (16 October 2025).
https://www.aicuris.com/press-release/aicuris-announces-pritelivir-met-primary-endpoint-in-immunocompromised-herpes-simplex-virus-infected-patients-in-phase-3-pivotal-trial - ClinicalTrials.gov. Potential Influence of Esomeprazole on the Pharmacokinetics of Pritelivir.
https://clinicaltrials.gov/study/NCT05513625 - ClinicalTrials.gov. Expanded Access Intermediate Size Treatment Protocol: Pritelivir for Immunocompromised Subjects with Treatment Resistant Herpes Simplex Virus Type 1 or 2.
https://clinicaltrials.gov/study/NCT05844436