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/microl. 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/microl 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).


CONCLUSIONS
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.
Lilleri
Daniele
D
Servizio di Virologia, IRCCS Policlinico S. Matteo, 27100 Pavia, Italy.
Piccinini
Giampiero
G
Baldanti
Fausto
F
Seminari
Elena
E
Galloni
Donata
D
Gerna
Giuseppe
G
D017088:AIDS-Related Opportunistic Infections / Q000209:etiology*; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D017726:Cytomegalovirus Retinitis / Q000188:drug therapy / Q000209:etiology*; D016049:Didanosine / Q000627:therapeutic use; D005500:Follow-Up Studies; D015774:Ganciclovir / Q000627:therapeutic use; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008213:Lymphocyte Activation; D008297:Male; D019829:Nevirapine / Q000627:therapeutic use; D012008:Recurrence; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D018119:Stavudine / Q000627:therapeutic use; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D019829:Nevirapine; D018119:Stavudine; D016049:Didanosine; D015774:Ganciclovir