Monitoring of human cytomegalovirus (HCMV)-specific CD4+ T cell frequency by cytokine flow cytometry as a possible indicator for discontinuation of HCMV secondary prophylaxis in HAART-treated AIDS patients.

Abstract

Absolute CD4+ T cell count and human cytomegalovirus (HCMV)-specific CD4+ T cell frequency (as determined by cytokine flow cytometry, CFC) were compared for their ability to predict HCMV disease and safe discontinuation of HCMV secondary prophylaxis. Three groups of AIDS patients with previous nadir CD4+ T cell count <100/microl were studied. Group A included 48 HAART-treated patients with no HCMV disease. Group B included 11 HAART-treated patients with previous HCMV disease who discontinued HCMV prophylaxis. Group C included 23 HAART-treated (n = 16) or -naive (n = 7) patients with previous HCMV disease either continuing or starting HCMV prophylaxis. Patients underwent follow-up for detection of HCMV viremia or disease (groups A and B) and for discontinuation of HCMV secondary prophylaxis on the basis of either HCMV-specific or absolute CD4+ T cell count (group C). During follow-up, while some patients showed a stable HCMV-specific CD4+ T cell response, others had a fluctuating response (unstable responders) or showed no response at all. In detail, 13/48 group A patients were either HCMV non-responders or unstable responders and 2 of them developed HCMV viremia; 3/11 group B patients were unstable responders, none developing either HCMV viremia or disease; finally, 9 group C patients discontinued HCMV prophylaxis based on absolute CD4+ T cell count > 150 cells/microl, but in 2 of them lacking HCMV-specific response HCMV retinitis relapsed. None of the seven group C patients discontinuing HCMV prophylaxis on the basis of CFC showed HCMV disease relapse. CFC may support absolute CD4+ T cell count for both guiding HCMV prophylaxis discontinuation and better monitoring HCMV infection in AIDS patients with no previous HCMV disease or having discontinued HCMV prophylaxis.