The Effects of Genetic Differences Among AIDS Patients on Cytomegalovirus Retinitis
Condition: AIDS
MeSH terms: Retinitis
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Patients with CMV Disease in AIDS cohort@@@@@@
      
Keywords: Retinitis; Cytomegalovirus; HIV-1; Polymorphisms; HAART