554   CMV-Specific CD4⁺T Lymphocyte Function in Long-Term Survivors of CMV Retinitis (CMVR) Receiving HAART.

M. A. Jacobson*¹, R. Schrier², J. M. McCune¹, F. Torriani², G. N. Holland³, J. J. O'Donnell¹, W. R. Freeman², and B. M. Bredt¹.
¹Univ. of California, San Francisco;²Univ. of California San Diego, La Jolla; and³Univ. of California at Los Angeles.

Background:Loss of CMV-specific T-cell response appears to be a key factor in the pathogenesis of CMVR. Serial monitoring of CMV-specific CD4⁺T lymphocyte response might help determine when long-term survivors of CMVR, on HAART but off anti-CMV therapy, are at risk for retinitis reactivation.

Methods:In an observational study, assays of peripheral blood for CMV-stimulated lymphocyte proliferation (LP) and CD4⁺T cell TH1-type cytokine expression by flow cytometry (CFC) were performed bimonthly in Group 1, patients with active CMV end-organ disease (retinitis or GI disease), and Group 2, CMVR survivors (>2 years) who had discontinued anti-CMV therapy in response to HAART without retinitis reactivation.

Results:Most Group 1 patients had negative CMV-specific CD4⁺T lymphocyte responses at entry by LP (6/6) or CFC (4/6), while all 10 Group 2 patients had>1 positive result by each assay at entry or during 6 months of follow-up. However, 40% of Group 2 patients also had>1 negative LP result and 50% had>1 negative CFC result during the study period, though none had retinitis reactivation during follow-up.

Conclusions:CMV-specific CD4⁺T lymphocyte responses were not consistently positive over time in many long-term survivors of CMVR despite their clinical stability off anti-CMV therapy. While neither CMV-specific LP nor CFC alone should be used to determine the need for CMV-specific antiviral therapy in such patients, these assays may be useful, when combined with absolute CD4⁺T cell counts, to identify long-term CMVR survivors most at risk for retinitis reactivation. Long-term survivors of CMVR should continue to be closely monitored, clinically and immunologically. New assays that can characterize CMV-protective immunity more accurately are needed.