Expression of p16(INK4a)  as a biomarker of T-cell aging in HIV-infected patients prior to and during antiretroviral therapy.
The p16(INK4a) tumor suppressor gene is a mediator of cellular senescence and has been suggested to be a biomarker of 'molecular' age in several tissues including T cells. To determine the association of both active and suppressed HIV infection with T-cell aging, T-cell p16(INK4a) expression was compared between 60 HIV+ suppressed subjects, 23 HIV+ untreated subjects, and 18 contemporaneously collected HIV-negative controls, as well as 148 HIV-negative historical samples. Expression did not correlate with chronologic age in untreated HIV+ patients, consistent with an effect of active HIV replication on p16(INK4a) expression. In patients on cART with suppressed viral loads, however, p16(INK4a) levels were similar to uninfected controls and correlated with chronologic age, with a trend toward an inverse correlation with CD4 count. These data show that p16(INK4a) is a reliable biomarker of T-cell aging in HIV+ patients with suppressed viral loads and suggest that poor CD4 cell recovery on cART may be associated with increased T-cell expression of p16(INK4a), a marker of cellular senescence.
UNC Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. jnelson@med.unc.edu
Julie A E
JA
Nelson
Janakiraman
J
Krishnamurthy
Prema
P
Menezes
Yan
Y
Liu
Michael G
MG
Hudgens
Norman E
NE
Sharpless
Joseph J
JJ
Eron
D000367:Age Factors; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis* / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D006801:Humans; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D019562:Viral Load
D044966:Anti-Retroviral Agents; D015415:Biomarkers; D019941:Cyclin-Dependent Kinase Inhibitor p16