Trial Information

Discovery of Genetic Variants Contributing to the Incidence or Course of CMV Disease in AIDS Patients

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.