Pritelivir Approved by the FDA for HSV Infections
This article is for general education only. It is not medical advice, and it should not replace the FDA label, infectious disease guidance, or a clinician’s judgment.
This month, the FDA approved Hovilpri (pritelivir) tablets for adults with weakened immune systems (e.g. individuals on immunosuppressive drugs, immunodeficiencies) who have lesions on their skin or mucous membranes due to herpes simplex virus type 1 and 2 (HSV-1 and HSV-2, respectively) and who have not responded to other therapies (acyclovir, valacyclovir, or famciclovir). This drug is an exciting addition to current HSV therapies (acyclovir, valacyclovir, and famciclovir) because it has a completely different mechanism of action and may be effective against treatment-resistant HSV disease.
HSV disease and standard antiviral treatment
HSV-1 and HSV-2 is dormant in sensory ganglia in the majority of adults. Virus can reactivate with immune suppression, stress, and skin trauma. During reactivation, virus can cause painful, fluid-filled blisters on the lips, face, fingers, and genital regions, as well as inside the nose and mouth. The lesions can spontaneously resolve or be treated with oral nucleoside analogs acyclovir, valacyclovir, or famciclovir. However, in some individuals, particularly those who have weakened immune systems, these nucleoside analogs are not effective in preventing recurrent disease.
Current alternatives for acyclovir-resistant HSV include drugs such as foscarnet or cidofovir, depending on the case. Those agents can be effective, but they may require intravenous dosing and careful toxicity monitoring, especially for kidney-related adverse effects. That is one reason an oral drug with a different mechanism has attracted interest.
How pritelivir works
Pritelivir blocks the HSV helicase-primase complex, a viral enzyme system the virus needs to copy its DNA. That complex helps unwind viral DNA and start the replication process. By blocking it, pritelivir interferes with HSV replication before the virus can efficiently build new DNA strands.
This is different from acyclovir in a clinically meaningful way.
Acyclovir is a nucleoside analog. It first needs activation inside HSV-infected cells. Viral thymidine kinase starts that activation process, then human cellular enzymes finish it. Once activated, acyclovir interferes with viral DNA polymerase and causes chain termination during DNA synthesis. Penciclovir acts in a similar fashion.
The thymidine kinase step is a strength and a weakness. It helps acyclovir target infected cells, which supports its favorable safety record. But many acyclovir-resistant HSV strains have mutations affecting viral thymidine kinase. If the virus cannot activate acyclovir well, acyclovir loses much of its effect.
Pritelivir does not rely on viral thymidine kinase activation. That is the main reason it may retain activity against some acyclovir-resistant HSV strains. In other words, acyclovir stops HSV DNA building after it is activated by the virus, while pritelivir blocks an earlier viral replication machine.
How pritelivir compares to acyclovir
The efficacy of Hovilpri was determined in a randomized, open-label, comparator-controlled, superiority trial (PRIOH-1 Phase 3 Trial, Part C; NCT 03073967) in immunocompromised participants with mucocutaneous HSV infection who did not respond to treatment with acyclovir, valacyclovir, or famciclovir. Participants received Hovilpri or the trial investigator’s choice of available treatments (nucleoside analogs) for up to 28 days until all lesions healed; the study was extended up to 42 days if lesions were improving but not completely healed after 28 days.
A total of 101 immunocompromised adults were randomly assigned and treated with Hovilpri or the investigator’s choice of available treatments. Immunosuppresive conditions included hematologic malignancy/disorder, hematopoietic stem-cell transplantation, HIV infection, autoimmune/inflammatory diseases, non-hematologic malignancies, or solid-organ transplantation.
The primary efficacy endpoint was the proportion of participants with all lesions healed during the treatment period up to 28 days. By 28 days, all lesions were healed in 63% of patients receiving Hovilpri, compared with 34% of patients receiving one of the other medications.
Another important difference are side effects. Acyclovir, as well as foscarnet and cidofivir, can cause nephrotoxicity and must be used with caution in individuals with kidney disease. Pritelivir is not associated with nephrotoxicity and the most common side effect is headache.
Feature | Pritelivir | Acyclovir |
Drug class | Helicase-primase inhibitor | Guanosine nucleoside analog |
Main viral target | HSV helicase-primase complex | HSV DNA polymerase after activation |
Activation requirement | Does not require viral thymidine kinase activation | Requires viral thymidine kinase activation |
Resistance relevance | May work against some acyclovir-resistant TK-mutant HSV | Resistance often involves thymidine kinase or DNA polymerase mutations |
Usual clinical role | FDA approved for resistant HSV | Standard HSV treatment and suppression in many settings |
Experience base | More limited | Decades of clinical use |
Notable side effects | Headache | Nephrotoxocity |
Summary
For routine HSV, proven agents such as acyclovir, valacyclovir, or famciclovir remain the standard of care. For suspected resistant HSV, especially in an immunocompromised individual, infectious disease consultation is often appropriate. If clinically appropriate, then pritelivir should be considered in resistant, difficult-to-treat HSV infections.
