Targeted Therapies for Immunological Non-Responders in People With HIV: A Multicenter Clinical Study

NCT07637877 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: KY-2025-11-209-2
• Study Type: interventional
• Target: 21
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Immunological Non-Responders in People With HIV

Outcome Measures

Primary Outcomes (1)

• CD4⁺ T cell count

  Baseline to week 36

Secondary Outcomes (1)

• Number of participants with treatment-emergent adverse events

  From baseline to 36 weekks

Study Arms (2)

cART

ACTIVE COMPARATOR

Participants receive standard combination antiretroviral therapy (cART) alone (without rilpivirine).

Drug: cART

cART plus Rilpivirine

EXPERIMENTAL

Participants receive standard combination antiretroviral therapy (cART) plus rilpivirine

Drug: cART

Interventions

cART DRUG

Participants receive standard combination antiretroviral therapy (cART) plus rilpivirine

cART; cART plus Rilpivirine

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• Co-infection with other viruses: positive for any of HBV, HCV, HDV, or HEV; or CMV/EBV viral load \> 1000 copies/mL.
• HIV-2 infection alone or co-infection with HIV-1 and HIV-2.
• History of using efavirenz or rilpivirine within 2 years prior to enrollment.
• History of NNRTI resistance.
• Clinical signs suggestive of other serious diseases.
• Long-term use of corticosteroids or other immunosuppressive agents.
• Co-existing severe AIDS-related or non-AIDS-related events.
• Co-existing severe underlying diseases of other systems not related to AIDS.
• Other severe organic diseases or psychiatric disorders, including any uncontrolled clinically significant disease of the urinary, circulatory, respiratory, nervous, psychiatric, digestive, endocrine, immune systems, or malignancy.
• Receipt of immunosuppressive or systemic cytotoxic therapy within 6 months prior to screening.
• Evidence of substance abuse within 6 months prior to enrollment, or a positive urine drug screen.
• Current participation in another clinical trial that may conflict with the treatment protocol or outcome measures of this study.
• Pregnancy, breastfeeding, or women who have a desire to become pregnant.
• Inability or unwillingness to provide informed consent or comply with study requirements.
• Any other serious condition that may interfere with the conduct of the clinical trial.

Sponsors & Collaborators

• Beijing 302 Hospital: lead
• Shenzhen Third People's Hospital: collaborator
• Third Affiliated Hospital, Sun Yat-Sen University: collaborator
• Guangzhou Eighth People's Hospital: collaborator

Central Study Contacts

Ruonan Xu, MD

CONTACT

+8618611314169; xuruonan2004@aliyun.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: The Fifth Medical Center of Chinese PLA General Hospital

Study Record Dates

• First Submitted: June 1, 2026
• First Posted: June 10, 2026
• Study Start: June 10, 2026
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 30, 2028
• Last Updated: June 10, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share