Close association of CD8+/CD38 bright with HIV-1 replication and complex relationship with CD4+ T-cell count.
BACKGROUND
Measuring lymphocyte activation provides information in addition to CD4(+) T-cell count for immune monitoring of HIV-1 infected patients. CD38 is a well-established activation marker that is generally analyzed on the whole population of CD8(+) T-cells. Focusing specifically on CD38 high expression (CD8(+)/CD38(bright)) may be an interesting surrogate gating strategy because CD38(bright) characterizes principally activated memory cells.


METHODS
CD8(+)/CD38(bright) was investigated in 1,353 HIV-1 infected patients over a one-year period to establish relevant cutoff values and clarify the relationships of this marker with HIV-1 RNA viral load (VL) and CD4(+) T-cell count.


RESULTS
The CD8(+)/CD38(bright) (>8,500 CD38 binding site per cells) is well correlated with HIV-1 VL (r = 0.87, P < 0.001) in this longitudinal follow-up of nonimmunodepressed patients that initiated antiviral therapy (ART). In aviremic patients on ART, the marker was highly predictive of VL rebound (sensitivity 93%, specificity 64% for a VL level of detection >200 copies/ml). While the CD8(+)/CD38(bright) moderately correlated with CD4(+) T-cell count independently of the VL (r = -0.37, P < 0.001), it increased dramatically in aviremic patient groups that exhibited profound CD4(+) T-cell depletion (median 39% for CD4(+) T-cell counts <50/mm(3)). This result indicates that other additional immunological and/or viral factors than readily detectable HIV-1 replication appears to be involved in T-cell activation of immunodepressed individuals.


CONCLUSIONS
CD8(+)/CD38(bright) is an effective marker for monitoring T-cell activation, which is a central factor of HIV-1 pathogenesis. This gating strategy requires only a single additional staining in conventional four color CD4 protocols.
Tuaillon
Edouard
E
Laboratoire de Virologie, Centre Hospitalier Universitaire de Montpellier, France.
Al Tabaa
Yassine
Y
Baillat
Vincent
V
Segondy
Michel
M
Picot
Marie-Christine
MC
Reynes
Jacques
J
Vendrell
Jean-Pierre
JP
D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism*; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D008137:Longitudinal Studies; D008213:Lymphocyte Activation / Q000276:immunology / Q000502:physiology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D012367:RNA, Viral / Q000032:analysis / Q000097:blood; D012680:Sensitivity and Specificity; D019562:Viral Load; D014779:Virus Replication / Q000276:immunology*
D044966:Anti-Retroviral Agents; D015415:Biomarkers; D008562:Membrane Glycoproteins; D012367:RNA, Viral; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1