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

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.