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

Daniele Lilleri, Giampiero Piccinini, Fausto Baldanti, Elena Seminari, Donata Galloni, Giuseppe Gerna

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Abstract

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.

Original languageEnglish
Pages (from-to)95-100
Number of pages6
JournalJournal of Clinical Virology
Volume26
Issue number1
DOIs
Publication statusPublished - Jan 2003

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Cytomegalovirus Retinitis
Highly Active Antiretroviral Therapy
CD4 Lymphocyte Count
Cytomegalovirus
Acquired Immunodeficiency Syndrome
T-Lymphocytes
Recurrence
HIV
Ganciclovir
Retinitis
Viremia
Mitogens
Candida
Cellular Immunity
Flow Cytometry
Cytokines

Keywords

  • AIDS
  • Cytokine flow cytometry
  • Human cytomegalovirus
  • Immune reconstitution
  • Lymphoproliferative response
  • Retinitis

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology
  • Virology
  • Immunology and Allergy
  • Infectious Diseases

Cite this

@article{ea0567e4f9174d1084c3be4e84e028b5,
title = "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",
abstract = "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.",
keywords = "AIDS, Cytokine flow cytometry, Human cytomegalovirus, Immune reconstitution, Lymphoproliferative response, Retinitis",
author = "Daniele Lilleri and Giampiero Piccinini and Fausto Baldanti and Elena Seminari and Donata Galloni and Giuseppe Gerna",
year = "2003",
month = "1",
doi = "10.1016/S1386-6532(02)00044-6",
language = "English",
volume = "26",
pages = "95--100",
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TY - JOUR

T1 - 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

AU - Lilleri, Daniele

AU - Piccinini, Giampiero

AU - Baldanti, Fausto

AU - Seminari, Elena

AU - Galloni, Donata

AU - Gerna, Giuseppe

PY - 2003/1

Y1 - 2003/1

N2 - 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.

AB - 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.

KW - AIDS

KW - Cytokine flow cytometry

KW - Human cytomegalovirus

KW - Immune reconstitution

KW - Lymphoproliferative response

KW - Retinitis

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U2 - 10.1016/S1386-6532(02)00044-6

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