LABORATORY MARKERS OF IMMINENT CYTOMEGALOVIRUS DISEASE

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Cytomegalovirus (CMV) is common infection, kept under control by the immune system. I can cause serious disease in patients whose immune systems are damaged by drugs required to prevent rejection of a transplanted organ. In these transplant patients, the detection of CMV in the blood (viremia) has been shown to predict which patients will develop disease. This information has been used to design controlled trials which have demonstrated clinical benefit from treatment of CMV infection before disease has developed (termed pre-emptive therapy). In the laboratory of the Principal Investigator, the quantity of CMV (virus load) has also been shown to correlate with CMV disease. Furthermore, previously identified risk factors in each of 3 distinct populations of transplant patients were no longer significant once virus load had been controlled for statistically. These results demonstrated that CMV load is the major determinant of CMV disease, and provide ways of optimizing the use of antiviral drugs with activity against CMV. This research project aims to apply to AIDS patients the same molecular virologic laboratory techniques which have been successfully evaluated in transplant patients. The patient groups are similar because their immunocompromised state allows CMV to become a common pathogen, but they are different because the range of organs affected is distinct. Preliminary results are presented to show that the lessons learned from studying the natural history and pathogenesis of CMV infection in transplant patients can be transferred to AIDS patients. Specifically, we hypothesize that: 1) CMV viremia will be shown to provide an early marker of imminent CmV disease. 2) Patients with viremia who develop CMV disease may have impaired neutralizing antibody activity. 3) The serial measurement of CMV viral load in patients being treated will identify those with inadequate initial therapy and those who develop resistant strains of CMV. 4) Better control of HIV replication with potent anti-retroviral drugs may improve immune control of active CMV infection and predict future decreases in CMV disease. In combination, all of these results will improve our understanding of CMV infection and the diseases it causes, will identify patients at high risk of CMV disease and so lead directly to controlled clinical trials aimed at reducing that disease in patients with HIV infection.