Impact of select immunologic and virologic biomarkers on CD4 cell count decrease in patients with chronic HIV-1 subtype C infection: results from Sinikithemba Cohort, Durban, South Africa.
BACKGROUND
The extent to which immunologic and clinical biomarkers influence human immunodeficiency virus type 1 (HIV-1) infection outcomes remains incompletely characterized, particularly for non-B subtypes. On the basis of data supporting in vitro HIV-1 protein-specific CD8 T lymphocyte responses as correlates of immune control in cross-sectional studies, we assessed the relationship of these responses, along with established HIV-1 biomarkers, with rates of CD4 cell count decrease in individuals infected with HIV-1 subtype C.


METHODS
Bivariate and multivariate mixed-effects models were used to assess the relationship of baseline CD4 cell count, plasma viral load, human leukocyte antigen (HLA) class I alleles, and HIV-1 protein-specific CD8 T cell responses with the rate of CD4 cell count decrease in a longitudinal population-based cohort of 300 therapy-naive, chronically infected adults with baseline CD4 cell counts >200 cells/mm(3) and plasma viral loads >500 copies/mL over a median of 25 months of follow-up.


RESULTS
In bivariate analyses, baseline CD4 cell count, plasma viral load, and possession of a protective HLA allele correlated significantly with the rate of CD4 cell count decrease. No relationship was observed between HIV-1 protein-specific CD8 T cell responses and CD4 cell count decrease. Results from multivariate models incorporating baseline CD4 cell counts (201-350 vs >350 cells/mm(3)), plasma viral load (< or =100,000 vs >100,000 copies/mL), and HLA (protective vs not protective) yielded the ability to discriminate CD4 cell count decreases over a 10-fold range. The fastest decrease was observed among individuals with CD4 cell counts >350 cells/mm(3) and plasma viral loads >100,000 copies/mL with no protective HLA alleles (-59 cells/mm(3) per year), whereas the slowest decrease was observed among individuals with CD4 cell counts 201-350 cells/mm(3), plasma viral loads < or =100,000 copies/mL, and a protective HLA allele (-6 cells/mm(3) per year).


CONCLUSIONS
The combination of plasma viral load and HLA class I type, but not in vitro HIV-1 protein-specific CD8 T cell responses, differentiates rates of CD4 cell count decrease in patients with chronic subtype-C infection better than either marker alone.
Brumme
Zabrina
Z
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Boston, USA.
Wang
Bingxia
B
Nair
Kriebashne
K
Brumme
Chanson
C
de Pierres
Chantal
C
Reddy
Shabashini
S
Julg
Boris
B
Moodley
Eshia
E
Thobakgale
Christina
C
Lu
Zhigang
Z
van der Stok
Mary
M
Bishop
Karen
K
Mncube
Zenele
Z
Chonco
Fundisiwe
F
Yuki
Yuko
Y
Frahm
Nicole
N
Brander
Christian
C
Carrington
Mary
M
Freedberg
Kenneth
K
Kiepiela
Photini
P
Goulder
Philip
P
Walker
Bruce
B
Ndung'u
Thumbi
T
Losina
Elena
E
D000328:Adult; D000483:Alleles; D015415:Biomarkers / Q000097:blood; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D013019:South Africa; D019562:Viral Load
D015415:Biomarkers; D006680:HLA Antigens