Status
Conditions
About
The health of the immune system in HIV infected people is currently determined from a blood test measuring the number of cluster of differentiation 4 (CD4) T lymphocytes. These cells play a critical role in an immune response. Studies have shown that low numbers (below the normal range) of CD4 T lymphocytes indicates a defect in the immune system. Conversely, the number of CD4 T lymphocytes within the normal range generally indicates a normal immune system. When a person is infected with HIV the CD4 T lymphocytes are attacked and destroyed and the numbers decline meaning that the immune system can no longer effectively protect the body from infection or cancers. However, when the HIV infected person is successfully treated with Highly Active Antiretroviral Therapy (HAART) the CD4 T lymphocytes numbers increase and may end up in the normal range but the immune system may still not function properly as a number of these cells are incapable of functioning properly.
It would be interesting to know how functional the immune system is rather than the number of cells. For this, the QuantiFERON® Monitor (QFM or CST007) test is an experimental diagnostic test used in this study to measure the immune function from people infected with HIV. The objective of this study is to evaluate the usefulness of the QFM test in HIV infected people compared with uninfected people by measuring the function of the immune system. The QFM test measures interferon-gamma released in the plasma following incubation of heparinised whole blood with a combination of stimulants. As immune function is directly influenced by cells with actively replicating HIV an additional research test called the HIV Reservoir Test will be included to better understand the level of immune function in each study subject.
How long will it take? One visit for about 1 hour with Dr. Gatpolintan and his Clinical Study Coordinator to answer questions, then about 10 minutes for a blood draw (nine blocks from Dr. Gatpolintan' office).
Study outcome measures (Correlation between QFM and CD4 counts and CD4/CD8 ratios) will be assessed, including data presentation, within an average period of 1 year after study subject enrollment.
Full description
Routine virologic and immunologic tests to monitor HIV-1 in infected individuals on highly active antiretroviral therapy (HAART) include CD4 T-cell enumeration, HIV-1 plasma viral load, and HIV-1 genotypic resistance testing at baseline for treatment-naive patients and following virologic failure during HAART.
The CD4 T-cell count is a measurement of the number of T helper lymphocytes and, in conjunction with the CD4/cluster of differentiation 8 (CD8) ratio, are surrogate markers to evaluate the status of the immune system and used to monitor the progression and define stages of HIV disease in infected subjects either on or off treatment. An increasing or high CD4 count and CD4/CD8 ratio between 1 and 4 suggests control of virus replication as a result of HAART (or from inherent immune activity in untreated subjects) while a decreasing or low CD4 count and a CD4/CD8 ratio <1 suggests HAART failure and/or a deteriorating immune system.
HIV-1 plasma viral load measures the number of HIV-1 RNA copies derived from virus particles in plasma. A detectable plasma viral load indicates HIV-1 replication while an undetectable plasma viral load suggests control of HIV-1 replication. Nevertheless, with the lower limit of detection of 50 copies HIV-1 RNA/mL for commercial assays, lower levels of plasma virus can remain undetected by these assays but detectable in approximately 70% patients on HAART using research assays with a cutoff of <50 copies HIV-1 RNA/ml. Such research based plasma viral load assays are never used for routine monitoring in the clinical care of infected subjects.
While CD4 counts and HIV-1 plasma viral load are inextricably related in the context of HIV-1 disease and currently the approved tests to determine HIV-1 response to HAART these assay have significant shortcoming for the effective treatment of HIV as defined below:
Consequently, increasing evidence demonstrates that CD4 counts and plasma viral load cannot be used to fully interpret the response of HIV to HAART. Moreover, mounting data proves that continued HIV-1 replication in the absence of detectable plasma viral load generates HIV and viral antigen resulting in immune activation thereby enabling HIV pathogenesis as demonstrated from increased levels of T cell turnover and proliferation, apoptosis of uninfected T cells as well as polyclonal B cell, natural killer (NK) cell and monocyte activation. Various cell based markers have been associated with HIV pathogenesis including immune activation markers Human Leukocyte Antigen (HLA)-Cell Surface Receptor (DR) (HLA-DR), cluster of differentiation 38 (CD38), cluster of differentiation 69 (CD69), cluster of differentiation 71 (CD71), senescence marker cluster of differentiation 57 (CD57), proliferation marker Ki67 and apoptosis marker cluster of differentiation 95 (CD95) (FasR). Altogether these markers of HIV pathogenesis enable inflammatory responses, reseeding reservoirs, HIV-1 evolution and drug resistance, and non-opportunistic diseases with a gradual deterioration of the immune system.
Immune function tests evaluate the functionality of a component of the immune system. They are generally in-vitro based assays and are designed to measure an outcome following exposure of lymphocytes to specific antigens or mitogens. The outcome may be the measurement of an immune stimulation marker such as secretion of gamma interferon, incorporation of tritiated thymidine into cellular genomic DNA as a result of a lymphoproliferative cell response to recall antigen and/or mitogen or, in the case of the in-vivo based Tuberculin Skin Test, the size of skin induration at the site of tuberculin purified protein derivative administration.
Cellestis Limited - A Qiagen Company, has recently developed the QuantiFERON® Monitor (QFM or CST007) test based on the patented QuantiFERON® Technology to provide a measure of the cell-mediated immune function. It is an in vitro diagnostic test that uses a combination of stimulants to specifically stimulate different immune cells in the whole blood and measures the interferon-gamma released in the plasma by ELISA (Enzyme-linked immunosorbent assay). Therefore, the aims of this study will address the utility of QFM in the HIV immunocompromised setting and as cell associated markers HIV pathogenesis influence immune function the HIV Viral Reservoir assay blood test will be included to better understand the level of immune function within and between cohorts.
How long will it take? One visit for about 1 hour with Dr. Gatpolintan and his Clinical Study Coordinator to answer questions, then about 10 minutes for a blood draw (nine blocks from Dr. Gatpolintan' office).
Study outcome measures (Correlation between QFM and CD4 counts and CD4/CD8 ratios) will be assessed, including data presentation, within an average period of 1 year after study subject enrollment.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Anti-retroviral drug naïve, (never on treatment, or >60 days off treatment), n=30
Successful HAART > 24 months with two undetectable plasma viral load within the last 12 months, n=30
On HAART > 24 months with latest plasma viral load >200, n=30
HIV Uninfected Controls (n=30):
Exclusion criteria
Key Exclusion Criteria for all HIV Infected only:
Key Exclusion Criteria for drug naïve HIV Infected only
Key Exclusion Criteria for HIV uninfected only:
Key Exclusion Criteria for all subjects:
How long will it take? One visit for about 1 hour with Dr. Gatpolintan and his Clinical Study Coordinator to answer questions, then about 10 minutes for a blood draw (nine blocks from Dr. Gatpolintan' office).
Loading...
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal