Declining levels of rescued lymphoproliferative response to human cytomegalovirus (HCMV) in AIDS patients with or without HCMV disease following long-term HAART

Giuseppe Gerna, Giampiero Piccinini, Emilia Genini, Elena Percivalle, Maurizio Zavattoni, Daniele Lilleri, Letizia Testa, Giuditta Comolli, Renato Maserati, Fausto Baldanti, Rita Maccario, Antonella D Arminio Monforte, Maria Grazia Revello

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Abstract

Objective: To investigate the lymphoproliferative response (LPR) to human cytomegalovirus (HCMV) in two groups of AIDS patients undergoing long-term highly active antiretroviral therapy (HAART): group 1 (n = 22) with nadir CD4+ T cell count + T-cell count and HCMV disease. All patients had previously undergone antiretroviral monotherapy or dual therapy before initiating HAART. Study Design and Methods: The two groups of patients were tested prospectively for CD4+ T cell count, HIV RNA load, HCMV viremia, and LPR to HCMV at baseline, and then after 3 and 4 years of HAART. A control group of 13 recently diagnosed treatment-naive AIDS patients with CD4+ T-cell counts + T-cell count increased significantly and to a comparable extent in the two groups of patients. In addition, the frequency of patients with HCMV viremia, although reduced, became comparable in both groups. After 4 years of HAART, the frequency of responders to HCMV without and with HCMV disease dropped to comparable levels (50.0 vs. 56.3%, respectively) in association with high median CD4+ T-cell counts and low median HIV RNA plasma levels. In parallel, the frequency of patients with HCMV viremia did not change significantly. In addition, after between 3 and 4 years of HAART, although the frequency of stable responders and nonresponders remained unchanged (50%) in both groups, most of the remaining patients showed declining levels of responsiveness to HCMV. Although some patients from both groups were found to have CD4+ T-cell counts >150/μl in the absence of LPR to HCMV, thus suggesting dissociation of specific and nonspecific immune reconstitution, a significant correlation was found between CD4+ T-cell count and LPR to HCMV (r = 0.44; p <.001). From a clinical standpoint, anti-HCMV therapy could be safely discontinued in 8 patients with HCMV retinitis showing CD4+ T-cell counts >150/μl, recovery of HCMV LPR, and no HCMV viremia. Conclusions: Declining levels of the previously recovered LPR to HCMV are often observed after long-term HAART. However, because the role of LPR in the evolution of HCMV infection and disease during HAART remains to be defined, the clinical impact of the declining LPR to HCMV must still be clarified in long-term prospective studies.

Original languageEnglish
Pages (from-to)320-331
Number of pages12
JournalJournal of Acquired Immune Deficiency Syndromes
Volume28
Issue number4
Publication statusPublished - Dec 1 2001

Fingerprint

Highly Active Antiretroviral Therapy
Cytomegalovirus
Acquired Immunodeficiency Syndrome
CD4 Lymphocyte Count
T-Lymphocytes
Viremia
Cell Count
HIV
RNA
Cytomegalovirus Infections

Keywords

  • CD4 T-cell count
  • HAART
  • HCMV disease
  • HCMV viremia
  • Human cytomegalovirus
  • Lymphoproliferative response
  • Stimulation index

ASJC Scopus subject areas

  • Virology
  • Immunology

Cite this

@article{7b0cf7de5bcf41fd8f9da477e1cc2c83,
title = "Declining levels of rescued lymphoproliferative response to human cytomegalovirus (HCMV) in AIDS patients with or without HCMV disease following long-term HAART",
abstract = "Objective: To investigate the lymphoproliferative response (LPR) to human cytomegalovirus (HCMV) in two groups of AIDS patients undergoing long-term highly active antiretroviral therapy (HAART): group 1 (n = 22) with nadir CD4+ T cell count + T-cell count and HCMV disease. All patients had previously undergone antiretroviral monotherapy or dual therapy before initiating HAART. Study Design and Methods: The two groups of patients were tested prospectively for CD4+ T cell count, HIV RNA load, HCMV viremia, and LPR to HCMV at baseline, and then after 3 and 4 years of HAART. A control group of 13 recently diagnosed treatment-naive AIDS patients with CD4+ T-cell counts + T-cell count increased significantly and to a comparable extent in the two groups of patients. In addition, the frequency of patients with HCMV viremia, although reduced, became comparable in both groups. After 4 years of HAART, the frequency of responders to HCMV without and with HCMV disease dropped to comparable levels (50.0 vs. 56.3{\%}, respectively) in association with high median CD4+ T-cell counts and low median HIV RNA plasma levels. In parallel, the frequency of patients with HCMV viremia did not change significantly. In addition, after between 3 and 4 years of HAART, although the frequency of stable responders and nonresponders remained unchanged (50{\%}) in both groups, most of the remaining patients showed declining levels of responsiveness to HCMV. Although some patients from both groups were found to have CD4+ T-cell counts >150/μl in the absence of LPR to HCMV, thus suggesting dissociation of specific and nonspecific immune reconstitution, a significant correlation was found between CD4+ T-cell count and LPR to HCMV (r = 0.44; p <.001). From a clinical standpoint, anti-HCMV therapy could be safely discontinued in 8 patients with HCMV retinitis showing CD4+ T-cell counts >150/μl, recovery of HCMV LPR, and no HCMV viremia. Conclusions: Declining levels of the previously recovered LPR to HCMV are often observed after long-term HAART. However, because the role of LPR in the evolution of HCMV infection and disease during HAART remains to be defined, the clinical impact of the declining LPR to HCMV must still be clarified in long-term prospective studies.",
keywords = "CD4 T-cell count, HAART, HCMV disease, HCMV viremia, Human cytomegalovirus, Lymphoproliferative response, Stimulation index",
author = "Giuseppe Gerna and Giampiero Piccinini and Emilia Genini and Elena Percivalle and Maurizio Zavattoni and Daniele Lilleri and Letizia Testa and Giuditta Comolli and Renato Maserati and Fausto Baldanti and Rita Maccario and Monforte, {Antonella D Arminio} and Revello, {Maria Grazia}",
year = "2001",
month = "12",
day = "1",
language = "English",
volume = "28",
pages = "320--331",
journal = "Journal of Acquired Immune Deficiency Syndromes",
issn = "1525-4135",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Declining levels of rescued lymphoproliferative response to human cytomegalovirus (HCMV) in AIDS patients with or without HCMV disease following long-term HAART

AU - Gerna, Giuseppe

AU - Piccinini, Giampiero

AU - Genini, Emilia

AU - Percivalle, Elena

AU - Zavattoni, Maurizio

AU - Lilleri, Daniele

AU - Testa, Letizia

AU - Comolli, Giuditta

AU - Maserati, Renato

AU - Baldanti, Fausto

AU - Maccario, Rita

AU - Monforte, Antonella D Arminio

AU - Revello, Maria Grazia

PY - 2001/12/1

Y1 - 2001/12/1

N2 - Objective: To investigate the lymphoproliferative response (LPR) to human cytomegalovirus (HCMV) in two groups of AIDS patients undergoing long-term highly active antiretroviral therapy (HAART): group 1 (n = 22) with nadir CD4+ T cell count + T-cell count and HCMV disease. All patients had previously undergone antiretroviral monotherapy or dual therapy before initiating HAART. Study Design and Methods: The two groups of patients were tested prospectively for CD4+ T cell count, HIV RNA load, HCMV viremia, and LPR to HCMV at baseline, and then after 3 and 4 years of HAART. A control group of 13 recently diagnosed treatment-naive AIDS patients with CD4+ T-cell counts + T-cell count increased significantly and to a comparable extent in the two groups of patients. In addition, the frequency of patients with HCMV viremia, although reduced, became comparable in both groups. After 4 years of HAART, the frequency of responders to HCMV without and with HCMV disease dropped to comparable levels (50.0 vs. 56.3%, respectively) in association with high median CD4+ T-cell counts and low median HIV RNA plasma levels. In parallel, the frequency of patients with HCMV viremia did not change significantly. In addition, after between 3 and 4 years of HAART, although the frequency of stable responders and nonresponders remained unchanged (50%) in both groups, most of the remaining patients showed declining levels of responsiveness to HCMV. Although some patients from both groups were found to have CD4+ T-cell counts >150/μl in the absence of LPR to HCMV, thus suggesting dissociation of specific and nonspecific immune reconstitution, a significant correlation was found between CD4+ T-cell count and LPR to HCMV (r = 0.44; p <.001). From a clinical standpoint, anti-HCMV therapy could be safely discontinued in 8 patients with HCMV retinitis showing CD4+ T-cell counts >150/μl, recovery of HCMV LPR, and no HCMV viremia. Conclusions: Declining levels of the previously recovered LPR to HCMV are often observed after long-term HAART. However, because the role of LPR in the evolution of HCMV infection and disease during HAART remains to be defined, the clinical impact of the declining LPR to HCMV must still be clarified in long-term prospective studies.

AB - Objective: To investigate the lymphoproliferative response (LPR) to human cytomegalovirus (HCMV) in two groups of AIDS patients undergoing long-term highly active antiretroviral therapy (HAART): group 1 (n = 22) with nadir CD4+ T cell count + T-cell count and HCMV disease. All patients had previously undergone antiretroviral monotherapy or dual therapy before initiating HAART. Study Design and Methods: The two groups of patients were tested prospectively for CD4+ T cell count, HIV RNA load, HCMV viremia, and LPR to HCMV at baseline, and then after 3 and 4 years of HAART. A control group of 13 recently diagnosed treatment-naive AIDS patients with CD4+ T-cell counts + T-cell count increased significantly and to a comparable extent in the two groups of patients. In addition, the frequency of patients with HCMV viremia, although reduced, became comparable in both groups. After 4 years of HAART, the frequency of responders to HCMV without and with HCMV disease dropped to comparable levels (50.0 vs. 56.3%, respectively) in association with high median CD4+ T-cell counts and low median HIV RNA plasma levels. In parallel, the frequency of patients with HCMV viremia did not change significantly. In addition, after between 3 and 4 years of HAART, although the frequency of stable responders and nonresponders remained unchanged (50%) in both groups, most of the remaining patients showed declining levels of responsiveness to HCMV. Although some patients from both groups were found to have CD4+ T-cell counts >150/μl in the absence of LPR to HCMV, thus suggesting dissociation of specific and nonspecific immune reconstitution, a significant correlation was found between CD4+ T-cell count and LPR to HCMV (r = 0.44; p <.001). From a clinical standpoint, anti-HCMV therapy could be safely discontinued in 8 patients with HCMV retinitis showing CD4+ T-cell counts >150/μl, recovery of HCMV LPR, and no HCMV viremia. Conclusions: Declining levels of the previously recovered LPR to HCMV are often observed after long-term HAART. However, because the role of LPR in the evolution of HCMV infection and disease during HAART remains to be defined, the clinical impact of the declining LPR to HCMV must still be clarified in long-term prospective studies.

KW - CD4 T-cell count

KW - HAART

KW - HCMV disease

KW - HCMV viremia

KW - Human cytomegalovirus

KW - Lymphoproliferative response

KW - Stimulation index

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M3 - Article

C2 - 11707667

AN - SCOPUS:0035575871

VL - 28

SP - 320

EP - 331

JO - Journal of Acquired Immune Deficiency Syndromes

JF - Journal of Acquired Immune Deficiency Syndromes

SN - 1525-4135

IS - 4

ER -