Allogeneic Adoptive Immune Therapy for Advanced AIDS Patients

Study Overview
=================
Brief Summary
-----------------
Combined antiretroviral therapy (ART) efficiently suppresses viral replication and markedly decreases mortality among patients with HIV-1 infection/AIDS. While the advanced AIDS patients with CD4+T cell count less than 200 cells/µL often develop seriously opportunistic infections (OIs), severe wasting syndrome, and other fatal complications, which are the major causes of death in these patients. There has been no effective immune therapy for advanced AIDS patients who had a high mortality rate even in the era of cART. This clinical trail is to inspect the efficiency of allogeneic adoptive immune therapy for advanced AIDS patients.

Detailed Description
-----------------
Combined antiretroviral therapy (ART) efficiently suppress viral replication and dramatically decrease mortality of the disease in HIV-1/AIDS patients.1 While in cART naive patients with chronic human immunodeficiency virus-1 (HIV-1) infection often characterized by HIV-1 replication, immune activation and deficiency, which lead to profound and systematic inflammation and pathoglogical change, especially in the AIDS patients with CD4 T count less than 50/uL, who often develop deadly complications, which accounts for the major cause of death group in spite of cART era. Up-to-date, there are no effective immune interventions to restore host holistic immunity for advanced AIDS patients. In pre-cARTera, HLA-matched lymphocytes or stem cell transplantation had been exploratively used in AIDS patients. However, this kind of therapy failed for immunological reconstitution due to the lack of antiviral therapy to suppress HIV-1 replication at that time. With the advent of cART, allogeneic HLA-matched or mismatched lymphocytes or stem cell transplantations were mainly used for AIDS patients with hematopoietic malignancies, the Berlin and London patients were the cured pateints. However, allogeneic transplantation can not be used outside the setting of hematopoietic malignancies. In addition, the high frequency of GVHD (Graft-versus-host disease) owning to a transient or long-lasting engraftment is inevitable. Until now, there has been no report of effective immune therapy for late-stage AIDS patients with acquired immunodeficiency and severe opportunistic infections (OIs). The urgent challenge is how to efficiently restore the host holistic immunity in AIDS patients at late stage. The investigators have recently developed a mismatched allogeneic adoptive immune therapy (AAIT) protocol in combination with cART, and found that the treatment was safety and tolerability in a phase I study. The purpose of this study is to further investigate the efficacy of allogeneic adoptive immune therapy (AAIT) for advanced AIDS patients. 120 patients received i.v. transfusion one round (2-3 times) of 2.0-3.0*10E8 cells/kg of MNSs as the treated group, all of these patients received the conventional cART treatment. In addition, the equal 120 patients received cART were used as control. The side effects, CD4 T cell numbers, HIV viral load, clinical symptoms improvement, control of opportunistic infections, AIDS-related events and non-AIDS related events will be evaluated during the 96-week follow up.

Official Title
-----------------
Safety and Efficiency of Allogeneic Adoptive Immune Therapy for Advanced AIDS Patients

Conditions
-----------------
AIDS Patients

Intervention / Treatment
-----------------
* Biological: Allogeneic Adoptive Immune Therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female, aged at 18 years (including) -65 years old Advanced AIDS patients with AIDS-related events Advanced patients with CD4 count less than or equal to 200 cells/uL, including end-stage patients with CD4 count less than or equal to 50 cells/uL before entry and at screening Sign informed consent, do not participate in other clinical trails during the period Exclusion Criteria: Pregnancy, lactation and those who are not pregnant but do not take effective contraceptives measures Combined with other serious organic diseases while didn't related with AIDS HIV-2 infection Allergic to blood products Under long term immunosuppressive therapy Combined with malignant tumors Drug addicts within half-one year before the test Poor compliance to antiviral therapy; take part in other clinical trials at present

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Conventional treatment plus Allogeneic Adoptive Immune Therapy<br>Participants will receive conventional treatment (anti-opportunistic infections, cART and other treatments) plus a dose (2-3 times) of Allogeneic Adoptive Immune Therapy | Biological: Allogeneic Adoptive Immune Therapy<br>* A dose (2-3 times) of AAIT was added on conventional treatment for advanced AIDS patients<br>|
| No Intervention: Conventional treatment<br>Without Allogeneic Adoptive Immune Therapy but conventional treatment (anti-opportunistic infections , cART and other treatments) should be received | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change of CD4+ T cell count between AAIT treatment group and conventional group | Marker for host immunity | At Baseline , week 4,12, 24, 48 and 96 | 
| The change of survival between AAIT treatment group and conventional group | Marker for efficacy of treatment | At week 24, 48 and 96 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
AIDS patients, Safety, Efficiency, Immune Therapy