TORONTO — Research conducted at The Toronto Hospital and the Canadian Red Cross Society appears to have unearthed a new way of detecting HIV infection which could lead to much earlier and faster diagnoses.

In a paper published in the journal Blood, dated Nov. 1, 1997, researchers David Phipps, from the Department of Oncology Research at The Toronto Hospital Research Institute, and Donald Branch, of the Canadian Red Cross, in Toronto, reported the discovery of a new marker for HIV which reduces the lag between the time of infection and time of detection.

Current HIV tests have a window period — the time of infection to the time of detection — anywhere from six weeks to six months. During this time, the unknowingly infected person could become a blood donor or have unprotected sex, putting others at risk.

Since the immune system of patients infected with HIV is in a state of chronic activation, the research focused on the known process of normal T cell activation, which involves early tyrosine phosphorylation.

The researchers homed in on an enzyme known as Fyn kinase. The protein tyrosine kinase Fyn is thought responsible for initiating the biochemical signals following activation of the T cell antigen receptor present on both CD4+ and CD8+ T lymphocytes

In their study, the researchers examined whether Fyn kinase activity is affected in patients with asymptomatic HIV when compared with uninfected control subjects. The deregulation of this critical T cell activation pathway may represent, they postulated, an important step in immune system abnormalities associated with HIV infection.

What they found was that patients with asymptomatic HIV infection had very low levels of Fyn protein compared to uninfected control subjects, but greatly elevated Fyn kinase activity.

Since the relative Fyn-specific kinase activity is elevated in patients with asymptomatic HIV infection and decreases in patients with AIDS, the researchers speculated that Fyn-specific kinase activity may be elevated shortly after infection, and this finding has the potential to be diagnostic of seronegative HIV infection. Lab experiments already have shown that Fyn kinase activity increases 30 minutes after HIV infection of human CD4+ T cells.

This is an important finding, commented Phipps, who was a postdoctoral fellow at The Toronto Hospital during the time the discovery was made and currently is manager of biotechnology and medical products with the Innovations Foundation, a technology licensing company founded by the University of Toronto.

According to Phipps, the marker could lead to new, early diagnostic methods for HIV. Initial research shows this test could actually replace current testing for HIV. Specifically, the test would be a surrogate test for the disease, since it does not test for HIV directly but rather for an enzyme that is activated in the HIV-infected state.

HIV infections normally are diagnosed by measuring antibodies produced in response to the infection. Unfortunately, there is a lag time between infection and production of antibodies and the antibody response is not useful for tracking the viral load of the infection, both of which are important issues in managing HIV infections.

At present, viral load is measured to monitor the effectiveness of therapies for HIV by nucleic acid assays, which are complex and costly. The new assay method, which does not rely on antibody or nucleic acid markers, is expected to find application in a number of areas for the management of HIV infections.

The researchers have applied for a patent and currently are collaborating on developing a screening kit for clinical testing with the pharmaceutical firm Select Therapeutics Inc., of Ottawa, Ontario.

No Comments