– Dr Moti Ramgopal
At IDWeek 2025, Dr Moti Ramgopal (Midway Immunology and Research Center, Florida, USA) discusses the first proof-of-concept clinical trial of pirmitegravir (STP0404), an allosteric integrase inhibitor (ALLINI) with a unique mechanism of action and potential to address integrase strand transfer inhibitor (INSTI) resistance.
In this Q&A, we discuss the findings from the Phase 2a trial, the drug’s unique mechanism of action, and its potential place in future HIV treatment strategies the first ALLINI to reach a proof-of-concept clinical trial.
Pirmitegravir differs from other INSTIs in its mechanism of action. Instead of binding directly to the integrase enzyme to inhibit its catalytic activity, it binds to an allosteric, or non-catalytic, site on integrase. This binding disrupts viral replication by mis-localising viral RNA, preventing proper viral assembly and resulting in the production of non-infectious viral particles. This unique mechanism may allow pirmitegravir to overcome resistance pathways that affect existing INSTIs.
The key findings regarding efficacy and tolerability included a mean decrease in viral load of 1.18–1.55 log<sub>10</sub> copies/mL from baseline to day 11. No severe or serious adverse events (AEs) were observed, and no participants discontinued due to AEs. All AEs resolved or recovered by the end of the trial, supporting the agent’s favourable safety and tolerability profile.
Pirmitegravir could potentially provide an important alternative within current HIV treatment strategies, particularly for individuals who have experienced failure on INSTI-based regimens or developed resistance. Its distinct resistance profile and novel mechanism of action make it a promising option for patients with limited treatment choices.
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This content has been developed independently by Touch Medical Media for touchINFECTIOUS DISEASES. Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.
Abstract: Ramgopal M, et al. 172 – The First Proof-of-Concept Clinical Trial of an HIV-1 Allosteric Integrase Inhibitor, Pirmitegravir (STP0404). Abstract #172. IDWeek 2025. October 19-22, Atlanta, GA, USA
Editor: Katey Gabrysch, Editorial Director.
Disclosures: This short article was prepared by touchINFECTIOUS DISEASES in collaboration with Moti Ramgopal. The content was developed and edited by human editors. No fees or funding were associated with its publication. touchINFECTIOUS DISEASES utilize AI as an editorial tool (ChatGPT (GPT-4o) [Large language model]. https://chat.openai.com/chat).
Moti Ramgopal discloses that he is a consultant for Gilead, Merck, and ViiV Healthcare; has received honoraria/honorarium from AbbVie, Gilead, Merck, and ViiV Healthcare; and is a speaker’s bureau participant for AbbVie, Gilead, and ViiV Healthcare.
Cite: Moti Ramgopal. First proof-of-concept trial of pirmitegravir: A novel allosteric integrase inhibitor for HIV-1. touchINFECTIOUS DISEASES. 10 November 2025.
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