Human cytomegalovirus (CMV) is a common pathogen in persons infected with HIV and has been frequently implicated as a possible cofactor in the development of progression of AIDS. Although extensive information is available regarding the clinical manifestations of CMV, questions remain as to: How to determine the presence of CMV disease? Which HIV-infected patients are at high-risk to develop visceral CMV? What virologic markers are predictive of disease? Is CMV resistance a frequent cause of treatment failure? In this proposal, we will develop assays to address these questions by utilizing specimens obtained from patients participating in ACTG protocols. In particular, we will extend our work which has demonstrated that CMV plasma viremia as detected by polymerase chain reaction (PCR) is correlated with buffy-coat culture positivity and visceral CMV disease.
The specific aims of this proposal are: (1) To determine if visceral organ involvement with CMV is associated with high levels of viral specific DNA, mRNA or proteins within plasma or circulating leukocyte populations by PCR, antigen detection and in situ hybridization; (2) To correlate detection of CMV specific DNA, mRNAs and proteins in leukocytes or plasma with development of visceral disease, disease progression and antiviral resistance; (3) To develop procedures for quantitative PCR for the detection of CMV DNA and mRNAs and for in situ hybridization PCR; and (4) To develop rapid and sensitive assays to screen for CMV resistance to antiviral agents directly from patient specimens. The studies proposed will develop molecular tools as markers of impending CMV disease, acute infection and disease progression, will improve methods for determining antiviral resistance and contribute to the understanding of the pathogenesis of CMV disease. The ultimate goal of this research is to develop effective methods for the diagnosis and monitoring of AIDS patients with CMV disease and thus, improve strategies for treatment and prevention.
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