Multiple relapses of human cytomegalovirus retinitis during HAART in an AIDS patient with reconstitution of CD4+ T cell count in the absence of HCMV-specific CD4+ T cell response

Background: While in the past human cytomegalovirus (HCMV) represented the major viral opportunistic pathogen in patients with AIDS, incidence of HCMV disease in HIV-infected patients drastically dropped after introduction of highly active antiretroviral therapy (HAART). However, cases of HCMV disease in HIV-infected patients treated with HAART have been reported. Objective: A 38-year-old HIV-infected patient developed HCMV retinitis in May 1999 after reaching a nadir of 69 CD4⁺ T cells/μl. HAART and anti-HCMV treatments with parenteral ganciclovir (GCV) were started, resulting in HIV viremia suppression, rise in CD4⁺ T cell count to >300 cells/μl and recovery from retinitis. Notwithstanding the apparent immune reconstitution, every attempt to discontinue GCV maintenance treatment was followed by a relapse of retinal lesions. Thus, HCMV-specific CD4⁺ cellular immune response was investigated. Results: Lymphoproliferation assay and cytokine flow cytometry analysis were performed repeatedly from November 1999 showing absolute lack of HCMV specific CD4⁺ T cell response, in the presence of an efficient lymphoprolipherative response against another pathogen (Candida) or a mitogen (Phytohemoagglutinin). Conclusion: In some patients, immune reconstitution after HAART may be only partial, since lack of pathogen-specific CD4⁺ T cell response may persist even in the case of a significant rise in the absolute CD4⁺ T cell count. This case suggests that immunologic assays investigating specific immune response against HCMV in HIV infected patients may be more useful than the CD4⁺ T cell count alone in assessing immune function reconstitution after HAART and in deciding interruption of anti-HCMV secondary prophylaxis.