4.4 Article

Old age and anti-cytomegalovirus immunity are associated with altered T-cell reconstitution in HIV-1-infected patients

Journal

AIDS
Volume 25, Issue 15, Pages 1813-1822

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAD.0b013e32834640e6

Keywords

age; antiretroviral therapy; cytomegalovirus; immunosenescence; lymphocytes

Funding

  1. INSERM AVENIR
  2. French ANRS
  3. ANR [ANR-09-JCJC-0114-01]
  4. Doris Duke Clinical Scientist Development Award
  5. UCSF Centers for AIDS Research at UCSF [PO AI27763]
  6. UCSF Clinical and Translational Science Institute [UL1 RR024131]
  7. NIAID [RO1 AI087145, K24AI069994]
  8. American Foundation for AIDS Research [106710-40-RGRL]
  9. Ragon Institute
  10. [K23 AI065244]
  11. Agence Nationale de la Recherche (ANR) [ANR-09-JCJC-0114] Funding Source: Agence Nationale de la Recherche (ANR)

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Objective and design: Increasing evidence supports a parallel between HIV-1 infection and immune aging, which is particularly apparent with common changes in naive versus memory T-cell proportions. Here, we aimed at refining the value of common T-cell-associated markers of immunosenescence during HIV disease progression or aging, and at exploring further the impact in this context of old age as well as cytomegalovirus (CMV) co-infection, which is predominant in HIV-1-infected individuals. Methods: Frequencies of naive or CD57(+) memory T cells as well as the magnitude of CMV-pp65 T cells were measured in HIV-1-infected patients grouped according to disease progression status, treatment and age. Results: Our results indicate that the decline in naive T-cell levels rather than the accumulation of CD57(+) senescent T cells identifies best the premature development of an immunosenescence phenotype with HIV disease progression. Moreover, advanced age or mounting of strong CMV-specific responses impact independently on CD4(+) T-cell counts and recovery with antiretroviral therapy. Conclusions: The present findings indicate that HIV-1 infection amplifies the effect of age on naive T-cell levels, and highlight the constraint on the capacity of treated patients to reconstitute their CD4(+) T-cell compartment due to age and CMV co-infection. (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

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