Residual HIV-specific CD4 and CD8 T cell frequencies after prolonged antiretroviral therapy reflect pretreatment plasma virus load.
BACKGROUND
Virus-specific cellular immune responses mediated by CD4 and CD8 T lymphocytes are thought to be central to the effective control of HIV-1 replication in vivo. However, quantitative correlations between HIV-specific T lymphocyte frequencies and plasma virus load (pVL) have proved difficult to establish in infected human individuals. This most likely reflects the complex interactions between the virus and these immune effector cells in the absence of treatment.


OBJECTIVE
To assess frequencies of HIV-specific T lymphocytes after prolonged suppression of viral replication, i.e., under conditions where the effects of virus on the immune response are standardized and minimized, thereby fixing an important variable in a dynamic multivariate system.


METHODS
HIV-specific CD4 and CD8 T lymphocyte frequencies were measured in 122 individuals after prolonged periods of successful combination antiretroviral therapy (ART) administered during chronic HIV-1 infection.


RESULTS
The residual frequency of both CD4 and CD8 T lymphocytes specific for HIV-1 was inversely related to the pretreatment pVL. This relationship appeared to be non-linear, indicating the presence of a threshold pretreatment pVL level above which HIV-specific CD4 and CD8 T lymphocyte responses could not be maintained when antigenic drive was suppressed. Substantial populations of functional HIV-specific CD4 and CD8 T lymphocytes were generally detectable after prolonged ART only in those individuals with a pretreatment plasma HIV-1 RNA < 100,000 copies/ml.


CONCLUSIONS
These findings identify a quantitative immune associate of host-virus interactions in established HIV-1 infection.
Oxenius
Annette
A
Nuffield Department of Medicine, John Radcliffe Hospital and Peter Medawar Building for Pathogen Research, Oxford, UK.
Price
David A
DA
Dawson
Sara J
SJ
Günthard
Huldrych F
HF
Fischer
Marek
M
Perrin
Luc
L
Ramirez
Elbe
E
Fagard
Catherine
C
Hirschel
Bernard
B
Scullard
George
G
Weber
Jonathan N
JN
McLean
Angela R
AR
Phillips
Rodney E
RE
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load
D019380:Anti-HIV Agents; D012367:RNA, Viral