Targeted Therapies for Immunological Non-Responders in People With HIV: A Multicenter Clinical Study
This study focuses on people with HIV who experience incomplete immune reconstitution despite suppressive antiretroviral therapy (ART), characterized by persistently low CD4⁺ T cell counts and residual inflammation. The underlying cause is largely attributed to the persistent HIV latent reservoir. Recent evidence indicates that rilpivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI) commonly used in ART, has an immunomodulatory function beyond its antiviral activity. It activates the CARD8 inflammasome - an intracellular kill switch - triggering pyroptosis selectively in HIV-infected cells. In this study, rilpivirine will be added to suppressive ART in patients with incomplete immune reconstitution. The investigators hypothesize that this strategy will reduce the latent reservoir, restore CD4⁺ T cell counts and function, attenuate excessive immune activation, and ultimately improve long-term clinical outcomes.
• Patients with incomplete immune reconstitution, aged between 18 and 65 years (inclusive).
• At enrollment, have received antiretroviral therapy (ART) for more than 4 years, with plasma HIV-RNA below the lower limit of detection (VL \< 50 copies/mL) for more than 3 years, while CD4⁺ T cell count remains persistently below 350 cells/μL.
• Within 1 year prior to enrollment, CD4⁺ T cell count remains persistently below 350 cells/μL but above 200 cells/μL.
• Currently receiving a dolutegravir (DTG)-based ART regimen (e.g., DTG plus lamivudine, or the fixed-dose combination DTG/3TC/ABC) for ≥ 1 year, with no relevant drug resistance detected by high-precision resistance testing; no change in the core ART regimen within 1 year prior to enrollment (adjustments of auxiliary medications for side effect management are permitted); and agree to continue the current integrase inhibitor-based regimen for at least 1 year after enrollment.
• Willing and able to provide written informed consent prior to any study-related procedures, and to comply with all study requirements.