The aim of this proposal is to test the potential clinical utility of a CMV-specific immunoassay that correlates with protective CMV-specific immune responses and which could inform clinicians when it is optimal to initiate, discontinue or re-institute anti-CMV therapy in order to prevent incident and progressive CMV retinitis (CMVR) in AIDS patients at risk for or already diagnosed with this opportunistic infection and thus prevent their future vision loss. The proposed work will investigate the hypothesis that CD8+ T lymphocyte IFNg responses (measured by flow cytometry after stimulation with short, overlapping peptides of the CMV pp65 and IE proteins, as well as with whole CMV lysate) will accurately predict clinical CMVR outcomes. Specifically, the primary objective is to compare CMV-stimulated CD8+/IFNg+ T lymphocyte responses by flow cytometry in stored PBMC samples obtained in the National Eye Institute-sponsored multi-center Longitudinal Study of the Ocular Complications of AIDS (LSOCA) from groups of cases prior to CMVR incident or progression events and from groups of matched control LSOCA subjects who had no subsequent incident or progressive CMVR event on study. The main secondary objective is to determine if additional clinical characteristics (use of HAART, use of anti-CMV therapy), standard clinical laboratory measurements (plasma HIV RNA, hemoglobin) or measurement of CMV viremia (by plasma CMV DNA) will enhance the predictive value of measuring CMV antigen-specific CD8+/IFNg+ T lymphocyte responses for incident or progressive CMVR. The proposed work will employ an observational, case-control study design. The study population will consist of subjects who have already been enrolled in LSOCA and currently have a median 2 years of follow-up. Extensive clinical data are collected as part of the LSOCA protocol and entered into a central database managed at the SOCA Coordinating Center at Johns Hopkins School of Public Health. PMBC specimens are obtained at all LSOCA-mandated study visits and banked in a central repository. The proposed work involves CMV-antigen specific immunoassay testing of stored PBMC specimens that have already been obtained and stored as part of the LSOCA protocol and then analyzing the relationship of the immunoassay results to other clinical data already collected as part of the LSOCA protocol, including CMVR outcomes that are confirmed by central masked analysis of retinal photographs. ? ?
| Jacobson, Mark A; Tan, Qi Xuan; Girling, Valerie et al. (2008) Poor predictive value of cytomegalovirus (CMV)-specific T cell assays for the development of CMV retinitis in patients with AIDS. Clin Infect Dis 46:458-66 |
