AIDS, HIV, Immune Checkpoint Inhibitors, Refractory Opportunistic Infection
Conditions
Brief summary
This prospective, single-arm, open-label study aims to evaluate the efficacy and safety of a PD-1 inhibitor (Sintilimab) combined with standard anti-infective therapy in patients with advanced HIV disease (AHD) who are suffering from refractory opportunistic infections (OIs). Despite effective antiretroviral therapy (ART), some HIV patients develop severe, hard-to-treat infections (such as CMV, PCP, Tuberculosis, etc.) that do not respond to standard antimicrobial treatments. This is often due to a condition called "immune exhaustion," where the body's infection-fighting T-cells become inactive and express high levels of a protein called PD-1. Sintilimab is an immune checkpoint inhibitor that blocks PD-1, effectively "waking up" the exhausted T-cells. While traditionally used for cancer, recent evidence suggests it can safely restore the immune system's ability to clear stubborn infections in HIV patients. In this study, eligible patients with refractory OIs and evidence of immune exhaustion will receive Sintilimab (200 mg intravenously every 3 weeks for a total of 3 doses) alongside their regular treatments. Researchers will monitor patient safety, clinical improvement, and immunological recovery.
Interventions
DRUGSintilimab
Sintilimab 200 mg dissolved in 100 ml normal saline, administered via intravenous infusion (60 minutes) once every 3 weeks for a total of 3 doses (Days 1, 22, and 43).
Sponsors
Shanghai Public Health Clinical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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: 1. 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. 2. Cytomegalovirus (CMV): Blood/body fluid CMV-DNA decrease \<1 log10 or new/worsening organ damage after 2 weeks of Ganciclovir or Foscarnet therapy. 3. Mpox virus: Unhealed lesions, new lesions, necrotic coalescence, or no decrease in viral load after 14 days of Tecovirimat, Cidofovir, or Brincidofovir therapy. 4. Progressive Multifocal Leukoencephalopathy (PML): Continuous deterioration of neurological symptoms or expanded lesion area on MRI after 3 months of optimized antiretroviral therapy (ART). 5. Pneumocystis jirovecii pneumonia (PCP): No improvement in oxygenation index or expanded radiological lesions after 8 days of adequate SMZ-TMP therapy. 6. Cryptococcal meningitis: Persistently positive cerebrospinal fluid (CSF) culture after 4 weeks of induction therapy. 7. Talaromyces marneffei / Invasive Aspergillosis: Persistently positive culture or progression of radiological/clinical symptoms after 2 weeks of Amphotericin B or Voriconazole therapy. 8. Mycobacterium tuberculosis (TB): Persistently positive sputum smear or culture after 2 months of standard anti-tuberculosis therapy. 9. 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.
Exclusion criteria
History of active autoimmune disease or autoimmune disease requiring systemic treatment. 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. 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathogen Clearance Rate | From enrollment to the end of treatment at 9 weeks | The proportion of patients achieving microbiological clearance (e.g., negative culture or negative PCR) of the specific refractory opportunistic infection. |
| Patient Mortality Rate | From enrollment to the end of treatment at 9 weeks | The proportion of patients who die from any cause during the study period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Related Adverse Events (TRAEs) | From enrollment to the end of treatment at 9 weeks | Safety will be assessed by recording the incidence and severity of adverse events related to the study drug, graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. |
Countries
China
Contacts
CONTACTJun Chen
Outcome results
None listed