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

A Study on the Efficacy and Safety of Immune Checkpoint Inhibitors in the Treatment of AIDS Complicated With Refractory Opportunistic Infections

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.

Study Overview

• Status: Not yet recruiting
• Conditions: HIV; AIDS; Immune Checkpoint Inhibitors; Refractory Opportunistic Infection
• Intervention / Treatment: Drug: Sintilimab

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jun Chen; Phone Number: 021-37990333; Email: chenjun@shaphc.org

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 201508
      • Shanghai Public Health Clinical Center
      • Contact: Jun Chen; Phone Number: 021-37990333; Email: chenjun@shaphc.org

Participation Criteria

Eligibility Criteria

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

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group; Patients with advanced HIV disease and refractory opportunistic infections receive Sintilimab combined with standard anti-infective therapy and antiretroviral therapy (ART).	Drug: Sintilimab; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathogen Clearance Rate	The proportion of patients achieving microbiological clearance (e.g., negative culture or negative PCR) of the specific refractory opportunistic infection.	From enrollment to the end of treatment at 9 weeks
Patient Mortality Rate	The proportion of patients who die from any cause during the study period.	From enrollment to the end of treatment at 9 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Related Adverse Events (TRAEs)	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.	From enrollment to the end of treatment at 9 weeks

Collaborators and Investigators

• Sponsor: Shanghai Public Health Clinical Center

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: May 6, 2026
• First Submitted That Met QC Criteria: May 6, 2026
• First Posted (Actual): May 12, 2026

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Opportunistic Infections; sintilimab
• Other Study ID Numbers: 2026-S017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) that underlie the results reported in the published article will be shared.
• IPD Sharing Time Frame: Data will become available beginning 6 months and ending 36 months following article publication.
• IPD Sharing Access Criteria: Data will be shared with qualified researchers who provide a methodologically sound proposal. Data will be used only to achieve the aims specified in the approved proposal. Proposals should be directed to the principal investigator or corresponding author via email. To gain access, data requestors will need to sign a formal data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No