Common diabetes medication may hold the key to long-term HIV remission without daily antiretroviral therapy

Gladstone scientists discover that metformin can activate "security lock" genes in immune cells to keep HIV dormant, paving a way toward treatment-free remission.

By: AXL Media

Published: Mar 21, 2026, 5:52 AM EDT

Source: Information for this report was sourced from Gladstone Institutes

Decoding the Mystery of HIV Controllers

For the vast majority of the millions living with HIV, antiretroviral therapy (ART) is a non-negotiable daily requirement. If treatment is interrupted, the virus typically rebounds from latent reservoirs within weeks. However, a small subset of individuals exhibits a rare ability to suppress the virus for months or even years without medication. Dr. Nadia Roan and her team at Gladstone Institutes have spent years studying these "controllers" to pinpoint the cellular features that keep the virus in a state of permanent sleep, aiming to replicate this effect in all patients.

The Discovery of Genetic Security Locks

The study’s most significant breakthrough is the identification of two specific genes, DDIT4 and ZNF254, found within the immune cells that serve as HIV reservoirs. These genes function as internal security locks that prevent the virus from "waking up" and replicating. Researchers found that patients with higher natural levels of these genes experienced significantly longer periods of remission after pausing therapy. Specifically, "elite controllers"—those who naturally suppress HIV without any drugs—were found to have exceptionally high levels of the ZNF254 gene.

Metformin as a Tool for Viral Suppression

The research link between the DDIT4 gene and delayed viral rebound has immediate clinical implications because of its relationship with metformin. Already a standard, low-cost treatment for Type 2 diabetes, metformin was found to actively boost the expression of the DDIT4 "lock" within T cells. In laboratory experiments, treating infected cells with metformin successfully blocked the ability of HIV to reactivate. This suggests that the drug could be repurposed to achieve a "block and lock" state, where the virus is first suppressed and then permanently silenced.