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

Inclusion criteria

• 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.

Exclusion criteria

• 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.