Parallel decline of CD8+/CD38++ T cells and viraemia in response to quadruple highly active antiretroviral therapy in primary HIV infection.
OBJECTIVE
To monitor changes in the numbers of CD8 lymphocytes expressing the activated CD38++ phenotype in peripheral blood samples from patients with primary HIV infection (PHI) treated with highly active antiretroviral therapy (HAART).


METHODS
Zidovudine, lamivudine, abacavir and amprenavir were initiated during PHI as part of the Quest study. Absolute numbers of CD8+/CD38++ T cells were determined using three-colour flow cytometry, and plasma viral load (VL) was measured using the Roche Amplicor method.


RESULTS
The median, pre-therapy CD8+/CD38++ T cell count was 461/mm(3)(interquartile range 216, 974) in 131 patients compared with normal control values of less than 20 cells/mm(3). Levels fell markedly in parallel with VL within the first 2 weeks of HAART initiation, to a median of 47 cells/mm(3) at 28 weeks (median 436 cell decline; P < 0.001). At that time, 80% of patients had a VL less than 50 copies/ml, and 16.3% of all patients had less than 20 CD8+/CD38++ T cells/mm(3). A continued decrease in CD8+/CD38++ T cell count occurred in 67.2% of patients whose VL was maintained below 50 copies/ml (median change from first to last value -18 cells/mm(3); P < 0.001).


CONCLUSIONS
After the initiation of HAART in PHI, CD8+/CD38++ lymphocytes declined rapidly in parallel with VL, and allowed for a normalization of CD8+/CD38++ T cell numbers in a subset of patients at week 28. Cell numbers continued to decline in patients who maintained VL below 50 copies/ml, indicating that the CD8+/CD38++ T cell count may represent a marker of residual viral replication when VL falls below detectable levels after HAART intervention.
Tilling
Richard
R
Department of Immunology and Molecular Pathology, Royal Free and University College Medical School, Royal Free Campus, London NW3 2QG, UK.
Kinloch
Sabine
S
Goh
Li-Ean
LE
Cooper
David
D
Perrin
Luc
L
Lampe
Fiona
F
Zaunders
John
J
Hoen
Bruno
B
Tsoukas
Chris
C
Andersson
Jan
J
Janossy
George
G
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology*; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers; D000071178:CD48 Antigen; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002219:Carbamates; D015224:Dideoxynucleosides / Q000627:therapeutic use*; D005260:Female; D005663:Furans; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D016896:Treatment Outcome; D019562:Viral Load; D014766:Viremia; D015215:Zidovudine / Q000627:therapeutic use*; D000099227:Abacavir
D019380:Anti-HIV Agents; D015703:Antigens, CD; D015415:Biomarkers; D000071178:CD48 Antigen; D002219:Carbamates; D015224:Dideoxynucleosides; D005663:Furans; D017320:HIV Protease Inhibitors; D019259:Lamivudine; D018894:Reverse Transcriptase Inhibitors; D013449:Sulfonamides; D015215:Zidovudine; D000099227:Abacavir; C095108:amprenavir