Trial Information

Phase 2 Study of UC-MSC in Restoring CD4 T Cell Counts and Reducing Immune Activation in HIV-infected Patients Underlying Long-term Antiviral Therapy: a Multicenter, Does-escalating, Randomized, Double-blind, Controlled Trial.

Although HIV-1 infection is characterized by progressive depletion of CD4+ T cells that
eventually leads to clinically significant immunodeficiency, a chronic generalized immune
activation is now being recognized to be the main driving force for T cell depletion, loss
of anti-HIV-1 immunity and disease progression during chronic HIV-1 infection. In
particular, this immune activation has been identified as a disease determinant independent
of viral load or cell death in HIV-1 infection. A series of clinical evidences have
indicated that activated CD8 T cells may attack body cells infected with viruses. Because of
this, CD4 cells infected with HIV are frequently destroyed by CD8 cells.

Mesenchymal stem cells (MSCs) are the adult stem cells originating from the mesenchymal and
connective tissue of bone marrow, adipose tissue, placenta, umbilical cord, cord blood,
peripheral blood, liver, etc. These cells show immunomodulation, self-renewal, and
multi-directional differentiation potential. In particular, MSCs have recently emerged as
promising candidates for cell-based immunotherapy because they can modulate the immune
response in various ways. A series of studies have indicated that secretion of dissoluble
cytokines and direct contact with MSCs can block the development and functioning of
antigen-presenting cells, inhibit the differentiation of B cells, and suppress the immune
response of T cells and natural killer cells. The immunosuppressive effect of infused MSCs
has been successfully employed in the treatment of acute severe graft-versus-host disease
(GVHD). Thus, MSC may reduce inflammatory responses and promote tissue recovery in human
diseases.

The purpose of this study is to learn what dose of transfused MSC reduces the level of
activation of CD8 cells in people infected with HIV. The decreased activation of CD8 cells
may lead to a more CD4 T cell restoration in HIV infection. This study will also look at
what dose of MSCs is tolerated and its safety in HIV- infected patients.

Participants in this study will be randomly assigned to one of three treatment arms:

Arm A:Participants will receive 48 weeks of low dose of MSC treatment followed by 48-week
follow-up observation.

Arm B:Participants will receive 48 weeks of high dose of MSC treatment followed by 48-week
follow-up observation.

Arm C: Participants will receive 48 weeks of saline placebo followed by 48-week follow-up
observation.

Study treatment will be given at 0, 4, 12, 24, 36 and 48 week since the onset of treatment.
There will be an additional 48 weeks of follow-up for purposes of safety. After treatment
has started, participants will be asked to come to the clinic on Weeks 4, 12, 24, 36,
48,60,72,84 and 96. At each visit participants will receive enough study treatment to last
until the next visit. Each visit will last between 2 and 3 hours. At most visits
participants will have a physical exam, answer questions about any medications they are
taking and how they are feeling, and have blood drawn for safety to assess CD4/CD8 cell
counts and viral load. Some additional blood will also be stored for immunology testing. At
some visits participants will be asked questions about their medication and medical history,
have pupils dilated, have a hearing test, and have an electrocardiogram (EKG). Some visits
will require participants to arrive fasting. Pregnancy tests may also be conducted if the
participant is able to become pregnant or if pregnancy is suspected.