IMMUNE BASED THERAPIES
Phase 1 Dose
Escalation Study of Autologous T-cells Genetically Modified at the CCR5 Gene by
Zinc Finger Nucleases in HIV-Infected Patients
The purpose of this research study is to find out whether
“zinc finger” modified CD4+ T-cells are safe to give to humans and
find how “zinc finger” modified T-cell affects HIV. Five
different cohorts with different patient characteristics are being recruited
Study of Cyclophosphamide in HIV-Infected Subjects on HAART Receiving Sangamo’s
The purpose of the study is to evaluate the safety,
tolerability and effect on HIV viral load, of escalating doses of cyclophosphamide
administered 1 day prior to SB-728-T infusion. It is hoped that
cyclophosphamide could improve engraftment of modified T cells.
Chemotherapy With Transplantation of Gene-Modified Stem Cells for High-Risk AIDS-Related Lymphoma
Patient stem cells will be
mobilized with induction chemotherapy (R)-ICE and G-CSF. If sufficient cells can be mobilized, patients will be treated with
high-dose chemotherapy and a transplant of autologous CD34+ cells transduced with an antiviral vector (M87o). If
autologous CD34+ yield is insufficient, allogeneic gene-modified cells will be given, if a compatible donor is
available. To minimize risk of transplant failure, a second unmodified CD34+ cell transplant will be given one week after the first
to Decrease Lymphoid Fibrosis in Antiretroviral-Treated, HIV-infected Patients:
A Pilot Study
The investigators propose a proof-of-concept,
pathogenesis-oriented, randomized, placebo-controlled pilot study to assess
whether the addition of an angiotensin converting enzyme (ACE) inhibitor to
standard Highly Active Antiretroviral Therapy (HAART) reverses lymphoid
fibrosis, and whether this leads to more effective HIV-specific host
immune responses and an accelerated clearance of the latent reservoir.
Efficacy Study of AGS-004 During Analytical Treatment Interruption
The purpose of this study is to determine the safety and
effectiveness of AGS-004, an immune therapy, for HIV-infected
individuals. Safety and effectiveness will be tested while the individuals are
both taking antiretroviral therapy (ART) medication and interrupting ART
Allogeneic Transplant in HIV Patients (BMT CTN 0903)
The rationale for this trial is to demonstrate the feasibility and safety of allogeneic HCT for patients with chemotherapy-sensitive hematological malignancies and coincident HIV-infection. In particular, the trial will focus on the 100-day non-relapse mortality as an indicator of the safety of transplant in this patient population. Correlative assays will focus upon the incidence of infectious complications in this patient population, the evolution of HIV infection and immunological reconstitution. Where feasible (and when this can be accomplished without compromise of either the donor quality or the timeliness of transplantation), an attempt will be made to identify donors who are homozygotes for the delta32 mutation for CCR5.
A randomized, double blind, phase IIB study testing the efficacy and safety of AGS-004 on host control of HIV replication during analytical treatment interruption
In this randomized, double blind, phase 2B trial, researchers will administer ASS-004 intradermally — into the skin — every four weeks at a dose of 1.2 x 10 7. In order for researchers to test AGS-004, participants will undergo a clinically controlled short-term analytical treatment interruption.
AGS-004 is created from a person’s own dendritic cells—white blood cells that stimulate the body’s immune system — and a sample of their HIV virus. This is the first experimental treatment designed from a person’s HIV genetic material and their body’s cells. Researchers believe that this study immunotherapy will boost anti-HIV immune responses in order to partially or totally control viral replication in the absence of ART or at least to significantly delay/limit the use of ART.
THERAPEUTIC HIV VACCINES
A Phase Il of a
Therapeutic, Recombinant, Biologically Active HIV-1 Tat Protein Vaccine in HIV-Infected, Anti-Tat Negative, ARV-Treated Adult Volunteers
Tat is a key HIV regulatory protein produced very early after
infection, prior to virus integration, and necessary for viral gene expression,
cell-to-cell virus transmission and disease progression. Previous studies in
natural HIV infection, indicated that the presence of a Tat-specific immune
response correlates with a lower incidence and reduced risk of progression to
AIDS as compared to anti-Tat negative individuals suggesting that an immune
response to Tat may exert a protective role and control the progression to AIDS
in vivo. Moreover Tat is conserved in its immunogenic regions (both B and T
cell) among all subtypes. subtypes. Recent data, in fact, indicate an effective
cross-clade recognition of clade B strain-derived (BH-10) Tat protein from the
HTLV-IIIB lab-adapted virus strain (Buttò, 2003), which was isolated about 20
years ago (Ratner, 1985), by sera from individuals infected with viruses
circulating at the present in Italy and in Africa, thus reflecting the high
degree of conservation of the corresponding Tat regions and providing strong
formal evidence that a Tat-based vaccine may indeed
be used in the different geographic areas of the world, since it is capable of
inducing a broad immune response against different virus clades. Based on this
rationale and on the positive results of preclinical (Cafaro, Nat Med 1999) and
phase I preventive and therapeutic clinical trials with Tat protein (ISS P-001
and ISS T-001, respectively) (Ensoli AIDS 2008, Vaccine 2009; LongoVaccine 2009; Bellino RRCT, 2009) a phase II therapeutic,
open label, clinical study with Tat protein (ISS T-002, ClinicalTrials.gov
NCT00751595) was sponsored by ISS and activated in 11 clinical sites in Italy
in HIV-infected HAART-treated
subjects.In this study, subjects are randomized into two arms to receive 3 or 5
vaccinations monthly; each arm is composed of two treatment groups, receiving
7, 5 or 30 µg of Tat, respectively. Preliminary results obtained from 87
subjects enrolled in the phase II trial ISST-002 ongoing in Italy, indicate
that Tat vaccination is safe, immunogenic and capable of reducing the immune
dysregulation which persists despite HAART in treated individuals, opening new
avenues for a most effective treatment of HIV/AIDS (Ensoli et al,PLoS ONE 2010).
Therapy and Improved Vaccination Responses by Cox-2 Inhibitor in HIV-infected Patients (OUSCOX2)
immune activation is a central feature of HIV-infection, and the degree of
activated T-cells is a better predictor of disease progression and mortality
than plasma viral load. The study hypothesis is that the anti-inflammatory
substance etoricoxib will dampen chronic immune activation and improve the
effect of T-cell dependent vaccines in HIV-1 infected patients.
The aim of the present study is to explore the efficacy of the
study drug on markers of immune activation and vaccine responses, as well as safety of the
study drug, in HIV-infected patients not receiving antiretroviral
Tolerability of a Therapeutic DNA Dendritic Cell Vaccine in HIV-Infected Children, Adolescents, and Young Adults
The therapeutic DNA vaccine, DermaVir, represents an immunization strategy
that targets lymph node dendritic cells. Because of the high percentage of
naive CD4 cells in children and adolescents, the potential for effective new
HIV-specific CD4 cell responses may be more achievable in children than in
adults. The primary purpose of this study is to evaluate the safety and
tolerability of DermaVir in children and young adults.
Immune Response Assessment Study of Killed-whole HIV-1 Vaccine (SAV001-H) in Chronic HIV-1 Infected Patients
The purpose of this study is to examine the safety,
tolerability, and immune response to killed-whole HIV-1 (SAV001-H) vaccine as a primary vaccination regimen in HIV infected individuals.
A Study to
Evaluate the Safety of the HIV-1 Vaccine MVA-B in
Chronic HIV-1 Infected
Patients Successfully Treated With HAART
30 treated chronic HIV-1 infected patients with CD4+ cell counts above
450 cells/ mm3 will be randomized 1:2 to receive placebo (n=10) or vaccine
(n=20) at week 0, 4 and 16 and will be observed at the Investigation Unit of
the study site for one hour following vaccination. At week 24 they will stop
their HAART until the end of the study.
Redirected High Affinity Gag‐Specific Autologous T Cells for HIV Gene Therapy
This research study uses a T cell receptor (TCR) protein specific for HIV (SL9 TCR) and adds it to the CD8 T‐cells in the laboratory in order to help the CD8 T‐cells recognize the constantly changing HIV virus and make it able to fight HIV more efficiently. TCR stands for T cell receptor TCRs are found on the surface of T cells and allow the T cells to recognize other cells. Laboratory studies have shown that when CD8 T‐cells are modified with SL9 TCRs, they kill cells that are infected with HIV better than normal CD8 T‐cells can. On the basis of these laboratory results, there is the potential that SL9 TCRs may work in people infected with HIV and improve their immune system by killing HIV infected cells and thus may help control HIV infection.
Two different SL9 TCRs will be tested in this study, WT‐gag‐TCR and α/6‐gag‐TCR. Two different types of SL9 TCRs are being used in this research study because the laboratory studies suggest that the different SL9 TCRs will function differently depending on the amount of virus in your body. A goal of this clinical study is to test the effects of infusions of either SL9 TCR in the presence or absence of a viral load.
Phase I/IIa Dose-escalation Clinical Study of VAC-3S
The purpose of this trial is to evaluate the safety and immunogenicity of the therapeutic vaccine candidate VAC-3S in HIV-1 infected patients under AntiRetroviral Therapy (ART) with undetectable viral loads.
Safety and Immunogenicity of HIVAX in HIV-1 Infected Subjects (GCHT01)
This study is to test a therapeutic HIV-1 vaccine (HIVAX™) in HIV-1 infected subjects. The safety and immune responses will be studied in vaccine recipients. The anti-viral effect of HIVAX vaccine will be monitored during a 12-week treatment interruption phase.
The Effect of
Vorinostat on HIV RNA Expression in the Resting CD4+ T Cells of HIV+ Pts on Stable ART
purpose of this study is to compare HIV RNA expression within resting CD4+
cells in HIV-infected patients on stable
ART before and after a single exposure to Vorinostat (VOR).
Hypotheses: The frequency of detectable HIV RNA expression within resting CD4+ T
cells will increase after VOR exposure in vivo.
The Study of Gut
Associated Lymphocytes in HIV and HCV/HIV Co-infected Patients
The purpose of this research study is to explore what role
immune cells within the gut (the sigmoid colon) have locally and on the immune
system of patients infected with HCV, HIV or HCV/HIV co-infection.
Effect on HIV Transcription of Vorinostat in Patients Receiving
Suppressive Combination Anti-retroviral Therapy
The objective of the study is to assess the safety and
ability of vorinostat, a drug currently licensed for the treatment of a type of
lymphoma, to ‘turn on’ dormant HIV infected
Levels of HIV Medications:
The aim of this study is to find out why HIV continues to
make copies in people taking HIV drugs. The Investigators want to know if the
medications most people use to treat HIV do not completely stop the virus from
making additional copies of HIV.
Impact Of Therapy Intensification By An Integrase Inhibitor +/- CCR5 Inhibitor
On The Lymphoid Reservoir For Hiv-1
the efficacy of adding Isentress®, with or without Celsentri®, to effective
conventional antiretroviral therapy (comprising at least 2 reverse
transcriptase inhibitors and one boosted protease inhibitor), on residual HIV
replication and blood cell and gut-associated lymphoid tissue reservoirs
(reverse transcriptase inhibitors: RTIs, boosted protease inhibitors: PI/r).
the effect of therapy intensification by means of an integrase inhibitor with
or without CCR5 inhibitor treatment on the lymphoid reservoir in patients
chronically infected with HIV-1, successfully treated with “conventional
triple therapy”, measured by:
plasma replication between 0 and 50 copies/ml
HIV RNA levels in circulating lymphocytes (PBMC) and lymphocytes in
gut-associated rectal lymphoid tissue (RL).
HIV DNA levels in PBMC and RL.
The Use of
Leukapheresis to Support HIV Pathogenesis Studies
A more complete understanding of the relationship between
inflammation and viral persistence is necessary before more rationale studies
of HIV eradication
can be designed. Also, a well validated high through-put virologic assay needs
to be developed that can estimate the size of the latent reservoir. Since the level
of replication competent virus in long-term treated patients (and in elite
controllers) is very small (< 1% of CD4 cells harbor HIV), large numbers of
lls most be obtained from study participants in order to
routinely isolate and quantify virus persistence.
2b Intensification in HIV-Positive
Individuals on Antiretroviral Therapy
Earlier studies of HIV-infected individuals who were not on any ART
showed that interferon reduced the level of HIV in the
blood. Researchers are interested in determining whether PEGINTRON therapy will
also reduce the residual low levels of HIV in
patients who are already taking ART.
Viral Load in
Blood and Lymph Tissues of HIV-Infected
Our laboratory has previously demonstrated that lymph nodes
are a major reservoir for human immunodeficiency virus (HIV) and a major site
of active virus replication in infected individuals(1-3). There is at least a
10 fold greater viral burden per given number of CD4+ T lymphocytes obtained
from the lymph nodes versus the peripheral blood in the same infected
individual. These data have been accumulated predominantly in individuals with
progressive generalized lymphadenopathy (CDC Class A1 and A2). It is unclear at
present whether this pattern holds true for all categories of HIV infected individuals. We have proposed that the
seeding of lymph nodes by HIV early in
the course of HIV infection
and the persistent production of virus in lymph nodes throughout the course of
infection are major factors in the pathogenesis of HIV in virtually all infected individuals.
Extreme ” Cohort (CODEX)
This cohort will allow common research projects with common
fundings and a better visibility both for clinicians who see patients with
unusual phenotypes and for international research. Such a cohort will be unique
in the world by its size and the presence of these two complementary groups of
patients. The two main objectives for the ” Extreme ” cohort (CODEX)
are clinical and immunovirological. The investigators wish to precise the
impact of a prolonged untreated HIV infection,
to describe the frequency of the “immunological escapes” (CD4 T cell
decrease) or “virological escapes” (permanent or transient viral load
increase). The investigators wish to study the genetic characteristics of the
patients and those of their viruses, the innate and adaptative immune responses
directed against HIV and other
viruses, the consequences of inflammation, and the characteristics of the loss
Role of extended-released niacin on immune activation in HIV-infected patients treated with antiretroviral therapy: a proof-of-concept study
This pilot study will evaluate the effect of a drug called Niaspan®, an extended-release form of niacin (ER niacin), in individuals living with HIV who are on antiretroviral therapy (ART). Researchers will examine the ability of an oral form of ER niacin to reduce immune activation and increase CD4 cells in persons with sub-optimal immune responses despite sustained virologic suppression from ART.
Study researchers believe that by regulating an amino acid called tryptophan, niacin may decrease T cell immune activation which may enhance CD4 recovery and improve neurocognitive functions. The effect of administering ER niacin in combination with ART will be measured against a regimen of ART alone.
Impact of HIV infection and antiretroviral therapy on mucosal and systemic memory CD4 T cells
This study will assess the impact of HIV infection and antiretroviral therapy on mucosal (gut) and systemic memory CD4 T cells in treatment-naïve HIV-positive individuals within six months of infection. Researchers believe this study will generate data to better understand how HIV harms the body and how they can use this information to better design HIV therapies and vaccines in the future.