Zadaxin and HIV-positive Patients With Immune Reconstitution Disorder

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of Zadaxin® in the treatment of HIV-positive patients with immune reconstitution disorders. Researchers previously used Zadaxin® (Thymosin α-1, Tα1) as an immune adjuvant for people infected with HIV-1 and found that Tα1 and Interferon-α (IFN-α) have a synergistic effect in immune enhancement. In addition, studies have found that the triple combination of Tα1, IFN-α and Zidovudine has better tolerability, safety and efficacy. After treatment, patients have lower HIV RNA and more stable high CD4+ T cell counts. In addition, extensive studies on the administration of Tα1 in thymectomized mice have demonstrated its ability to promote immune reconstitution. The researchers hypothesized that Zadaxin® has a better therapeutic effect on HIV-positive patients with immune reconstitution disorders, can increase the CD4+T cell count, reduce the viral load, and has better safety.

Detailed Description
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All patients received Zadaxin (1.6 mg subcutaneous injection, once a day) in the first 2 weeks, and changed frequency (1.6 mg subcutaneous injection, twice a week) in the successive 22 weeks. It is still recommended to continue treatment until the end of the study. All subjects were given HAART treatment throughout. In 4th week, 8th week, 12th week and 24th week, perform 4 follow-up and record the changes in CD4+ T cell count and proportion, CD8+ T cell count and proportion, proportions of T cell subsets, PBMC sjTREC, proportions of exhauseted T cell expressed PD-1 and Tim-3, and HIV viral load. During the process, safety assessment is performed, including adverse events, electrocardiogram and a series of laboratory tests (blood routine, liver and kidney function, etc.).

Official Title
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A Prospective Single-arm Cohort Study Evaluating the Safety and Efficacy of Thymalfasin (Zadaxin®) in the Treatment of HIV-positive Patients With Immune Reconstitution Disorders

Conditions
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HIV-1-infection

Intervention / Treatment
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* Drug: Zadaxin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-65 years old; HIV serology is positive; Volunteer to participate; CD4+T cell count >100 and <350 cells/mm3; People who have received HAART treatment and the viral load is undetected for at least 2 years, but have immune reconstitution disorder; Without active opportunistic infection; Exclusion Criteria: History of allergy or contraindications to Zadaxin; Skin basal cell carcinoma, cervical carcinoma in situ or other concurrent tumors other than Kaposi's sarcoma; The expected survival time is less than 1 year; Women of childbearing age have a positive pregnancy test; Major heart disease or central nervous system disease or other nervous system abnormalities; ACTG-AIDS dementia syndrome staging score> 0.5; Organ transplantation; Received chemotherapy and radiotherapy for malignant tumors within 6 months; Known immunomodulators (such as systemic steroids, interferons, interleukins) or other immunotherapy within 30 days before the start of the study; Blood transfusion within 30 days before the start of the study; Have a history of iritis, endophthalmitis, scleritis or retinitis; Within 30 days before the screening assessment, accept any experimental treatment for HIV-positive patients with or without symptoms of infection; Drug abuse; The doctor's decision is that participation in the trial is not in the patient's best interests, or any situation that does not allow safe compliance with the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: All participants eligible for study received the same open label drug
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zadaxin-HIV(n=20)<br>Study participants will be given Zadaxin (1.6 mg subcutaneous injection, once a day) in the first 2 weeks, and changed frequency (1.6 mg subcutaneous injection, twice a week) in the successive 22 weeks. | Drug: Zadaxin<br>* 1.6 mg subcutaneous injection, once a day in the first 2 weeks, and 1.6 mg subcutaneous injection, twice a week in the successive 22 weeks.<br>* Other names: Thymosin α1;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in CD4+T cell counts | Peripheral blood | Measured on week 24 | 
| Change in CD4/CD8 ratio | Peripheral blood | Measured on week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in CD4+T cell count and proportion | Peripheral blood | Measured on week 0, 4, 8, 12, 24 | 
| Change in CD8+T cell count and proportion | Peripheral blood | Measured on week 0, 4, 8, 12, 24 | 
| Change in proportions of T cell subsets | Peripheral blood mononuclear cell | Measured on week 0, 4, 8, 12, 24 | 
| Change in proportions of immune exhausted T cells expressed PD-1 and TIM-3 | Peripheral blood mononuclear cell | Measured on week 0, 4, 8, 12, 24 | 
| Change in PBMC sjTREC | Peripheral blood mononuclear cell | Measured on week 0, 4, 8, 12, 24 | 
| Change in HIV-1 RNA | Plasma | Measured on week 0, 4, 8, 12, 24 |