Efficacy and Safety of Immune Checkpoint Inhibitors for Refractory Opportunistic Infections in AIDS

Ki vehet részt

• Age ≥ 18 years. Confirmed HIV-1 infection
• Must have at least one opportunistic infection meeting the "refractory" criteria after currently available standard anti-infective treatment, defined as follows:
• Parvovirus B19: Hemoglobin (Hb) fails to recover (increase <10g/L) or requires transfusion maintenance, with reticulocytes persistently <1% after 4 weeks of Intravenous Immunoglobulin (IVIG) therapy
• Cytomegalovirus (CMV): Blood/body fluid CMV-DNA decrease <1 log10 or new/worsening organ damage after 2 weeks of Ganciclovir or Foscarnet therapy
• Mpox virus: Unhealed lesions, new lesions, necrotic coalescence, or no decrease in viral load after 14 days of Tecovirimat, Cidofovir, or Brincidofovir therapy
• Progressive Multifocal Leukoencephalopathy (PML): Continuous deterioration of neurological symptoms or expanded lesion area on MRI after 3 months of optimized antiretroviral therapy (ART)
• Pneumocystis jirovecii pneumonia (PCP): No improvement in oxygenation index or expanded radiological lesions after 8 days of adequate SMZ-TMP therapy
• Cryptococcal meningitis: Persistently positive cerebrospinal fluid (CSF) culture after 4 weeks of induction therapy
• Talaromyces marneffei / Invasive Aspergillosis: Persistently positive culture or progression of radiological/clinical symptoms after 2 weeks of Amphotericin B or Voriconazole therapy
• Mycobacterium tuberculosis (TB): Persistently positive sputum smear or culture after 2 months of standard anti-tuberculosis therapy
• Nontuberculous mycobacteria (NTM): No improvement in clinical symptoms after 1 month of standard therapy, or culture not turning negative after 3 months; High PD-1 expression on peripheral CD8+ T cells (>25%) OR weak pathogen-specific ELISpot response (<50 SFCs/10\^6 cells); Agreement to use highly effective contraception during the study and for 6 months after the end of the trial; Voluntary signing of informed consent

Ki nem vehet részt

• Prior organ transplantation or hematopoietic stem cell transplantation. Pregnant or lactating women. Known allergy or anti-drug antibodies to the study drug or its excipients. Prior treatment or exposure to any other immune checkpoint inhibitors. Received immunomodulatory or immunosuppressive therapy (excluding glucocorticoids) within 24 weeks prior to the first dose of the study drug
• History of active autoimmune disease or autoimmune disease requiring systemic treatment
• Psychiatric disorders or substance abuse that may interfere with the trial. Other severe medical conditions deemed by the investigator as unsuitable for trial participation (e.g., uncontrolled severe heart, liver, or renal failure)