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.

Study Overview

• Status: Not yet recruiting
• Conditions: Immunological Non-Responders in People With HIV
• Intervention / Treatment: Drug: cART

• Study Type: Interventional
• Enrollment (Estimated): 21
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ruonan Xu, MD; Phone Number: +8618611314169; Email: xuruonan2004@aliyun.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with incomplete immune reconstitution, aged between 18 and 65 years (inclusive).
2. 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.
3. Within 1 year prior to enrollment, CD4⁺ T cell count remains persistently below 350 cells/μL but above 200 cells/μL.
4. 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.
5. Willing and able to provide written informed consent prior to any study-related procedures, and to comply with all study requirements.

Exclusion Criteria:

1. Co-infection with other viruses: positive for any of HBV, HCV, HDV, or HEV; or CMV/EBV viral load > 1000 copies/mL.
2. HIV-2 infection alone or co-infection with HIV-1 and HIV-2.
3. History of using efavirenz or rilpivirine within 2 years prior to enrollment.
4. History of NNRTI resistance.
5. Clinical signs suggestive of other serious diseases.
6. Long-term use of corticosteroids or other immunosuppressive agents.
7. Co-existing severe AIDS-related or non-AIDS-related events.
8. Co-existing severe underlying diseases of other systems not related to AIDS.
9. 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.
10. Receipt of immunosuppressive or systemic cytotoxic therapy within 6 months prior to screening.
11. Evidence of substance abuse within 6 months prior to enrollment, or a positive urine drug screen.
12. Current participation in another clinical trial that may conflict with the treatment protocol or outcome measures of this study.
13. Pregnancy, breastfeeding, or women who have a desire to become pregnant.
14. Inability or unwillingness to provide informed consent or comply with study requirements.
15. Any other serious condition that may interfere with the conduct of the clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: cART; Participants receive standard combination antiretroviral therapy (cART) alone (without rilpivirine).	Drug: cART; Participants receive standard combination antiretroviral therapy (cART) plus rilpivirine
Experimental: cART plus Rilpivirine; Participants receive standard combination antiretroviral therapy (cART) plus rilpivirine	Drug: cART; Participants receive standard combination antiretroviral therapy (cART) plus rilpivirine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
CD4⁺ T cell count	Baseline to week 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-emergent adverse events	Safety will be assessed by monitoring and recording all adverse events (AEs), serious adverse events (SAEs), and AEs leading to treatment discontinuation. Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	From baseline to 36 weekks

Collaborators and Investigators

• Sponsor: Beijing 302 Hospital
• Collaborators: Third Affiliated Hospital, Sun Yat-Sen University; Shenzhen Third People's Hospital; Guangzhou Eighth People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 10, 2026
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 30, 2028

Study Registration Dates

• First Submitted: June 1, 2026
• First Submitted That Met QC Criteria: June 4, 2026
• First Posted (Actual): June 10, 2026

Study Record Updates

• Last Update Posted (Actual): June 10, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: KY-2025-11-209-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No