The Effects of Genetic Differences Among AIDS Patients on Cytomegalovirus Retinitis

Overview

This study will evaluate the role of certain gene variants on the onset and course of cytomegalovirus (CMV) retinitis-a severe infection affecting the eye-in patients with AIDS. Symptoms include blurry vision, eye pain, photophobia, floaters, eye redness, and impaired vision. Left untreated, it can cause blindness. The study is done in collaboration with investigators of the Longitudinal Studies of the Ocular Complications of AIDS (LSOCA) at the Johns Hopkins University School of Medicine. The purpose of the LSOCA study is to learn about how HIV and other infections associated with AIDS and their treatments affect people's eyes and sight. Blood samples previously collected from patients participating in the LSOCA study will be analyzed for gene variants. These differences will then be correlated with the patients' clinical data to try to discover the role of gene differences among patients on the following: susceptibility to CMV and related problems; development and course of CMV; and response to HAART (highly active antiretroviral treatment), particularly in CMV onset and pathology. The study will use blood samples and clinical information previously collected from patients during their participation in LSOCA. The materials will be identified with a numerical code linking the samples and clinical data. No additional procedures will be performed on patients for this study.

Background: LSOCA is a prospective observational study of ocular complications in HIV-infected AIDS patients including those treated with highly active anti-retroviral treatment (HAART). In the absence of HAART, there is a 30% risk of cytomegalovirus (CMV0 infection associated with AIDS. Of these CMV patients, 75-85% will develop retinitis. Objectives: Test a number of human candidate gene polymorphisms in the LSOCA cohort samples to discover genetic influences on the susceptibility to CMV and associated pathologies. Inspect the role of known AIDS restriction genes (ARGs) on the infection and pathogenesis of CMV. Evaluate the role of the same host gene polymorphisms on the response to HAART, particularly in CMV onset and pathology. Eligibility: Lymphocytes for DNA extraction and relevant clinical data from properly consented AIDS patients (maximum estimated at n= 2,000) will be provided to the LGD for genotyping and analysis. No available subjects will be excluded. Design: LSOCA has collected blood specimens and banked viably frozen lymphocytes from each study participant. Samples and clinical data are coded and linked. Genes under study include the traditional described ARGs (O'Brien \& Nelson, 2004); the CMV receptor gene, US28 (Pleskoff et al., 1997); HLA class I and II; KIR gene family and other genes involved in virus immune defenses. Single nucleotide variants within coding regions, upstream and downstream regulatory regions, and ironic elements will be tested for genetic equilibrium distortion in patient populations at risk for CMV and displaying CMV pathology. Following this study, the samples will be maintained in our repository and curated through our central Laboratory database. Loss or destruction of these samples will be recorded in our database and cannot impact the study participants in any way. We understand that studies subsequent to the completion of this protocol will require additional OHSR/IRB approval prior to commencement.