TY - JOUR
T1 - CD4 T cell nadir independently predicts the magnitude of the HIV reservoir after prolonged suppressive antiretroviral therapy
AU - Boulassel, Mohamed Rachid
AU - Chomont, Nicolas
AU - Pai, Nitika Pant
AU - Gilmore, Norbert
AU - Sékaly, Rafick Pierre
AU - Routy, Jean Pierre
N1 - Funding Information:
This project was funded in part by The American Foundation for AIDS Research (amfAR#106722-40RGRL), the Canadian Foundation for AIDS Research (CANFAR #017-718), The Canadian HIV Trials Network-Canadian Institutes of Health Research (CTN-CIHR #CTN 205), Fonds de la recherche en santé du Québec (FRSQ), Sida et maladies infectieuses and Canadian Institutes of Health Research (CIHR #HOP-103230).
PY - 2012/1
Y1 - 2012/1
N2 - Background: The level of HIV-1 integrated DNA in CD4 T cells was reported to predict the evolution of untreated HIV-1 infection independently of CD4 cell counts or plasma HIV-1 RNA levels. However, the relevance of reservoir level while on efficient antiretroviral therapy (ART) is still unknown. Objectives: To evaluate factors that may contribute to the establishment and maintenance of HIV-1 reservoir size in ART-treated HIV-1-infected adults with complete suppression of viremia. Study design: 35 subjects receiving ART with plasma HIV-1 RNA below the limit of detection for an average duration of 3.2 years were studied. A highly sensitive PCR was used to assess HIV-1 integrated DNA levels in sorted CD4 T cells. Results: The mean HIV-1 integrated DNA was 300±7copies/10 6 CD4 cells (range 10-1408). In univariate analysis, the levels of HIV-1 proviral DNA appeared to be independent of duration of HIV-1-infection, duration on ART, time since HIV-1 viral load was undetectable, delay between HIV-1 infection and starting ART, or viral load before starting ART. Conversely, CD4 T cell nadir, CD4/CD8 ratio and, to lesser degree, CD4 T cell counts were inversely associated with HIV-1 proviral DNA levels. In multivariate analysis, only CD4 T cell nadir significantly predicted levels of HIV-1 proviral DNA (P=0.025). Conclusions: CD4 T cell nadir strongly predicted reservoir size independently of other factors in HIV-1-infected adults with complete suppression of viremia. Collectively, these results indicate that the extent of CD4 T cell depletion before ART drives the size of the viral reservoir after prolonged therapy.
AB - Background: The level of HIV-1 integrated DNA in CD4 T cells was reported to predict the evolution of untreated HIV-1 infection independently of CD4 cell counts or plasma HIV-1 RNA levels. However, the relevance of reservoir level while on efficient antiretroviral therapy (ART) is still unknown. Objectives: To evaluate factors that may contribute to the establishment and maintenance of HIV-1 reservoir size in ART-treated HIV-1-infected adults with complete suppression of viremia. Study design: 35 subjects receiving ART with plasma HIV-1 RNA below the limit of detection for an average duration of 3.2 years were studied. A highly sensitive PCR was used to assess HIV-1 integrated DNA levels in sorted CD4 T cells. Results: The mean HIV-1 integrated DNA was 300±7copies/10 6 CD4 cells (range 10-1408). In univariate analysis, the levels of HIV-1 proviral DNA appeared to be independent of duration of HIV-1-infection, duration on ART, time since HIV-1 viral load was undetectable, delay between HIV-1 infection and starting ART, or viral load before starting ART. Conversely, CD4 T cell nadir, CD4/CD8 ratio and, to lesser degree, CD4 T cell counts were inversely associated with HIV-1 proviral DNA levels. In multivariate analysis, only CD4 T cell nadir significantly predicted levels of HIV-1 proviral DNA (P=0.025). Conclusions: CD4 T cell nadir strongly predicted reservoir size independently of other factors in HIV-1-infected adults with complete suppression of viremia. Collectively, these results indicate that the extent of CD4 T cell depletion before ART drives the size of the viral reservoir after prolonged therapy.
KW - Antiretroviral therapy
KW - HIV-1
KW - Nadir CD4 T cells
KW - Reservoir
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U2 - 10.1016/j.jcv.2011.09.018
DO - 10.1016/j.jcv.2011.09.018
M3 - Article
C2 - 22019250
AN - SCOPUS:83355173944
SN - 1386-6532
VL - 53
SP - 29
EP - 32
JO - Journal of Clinical Virology
JF - Journal of Clinical Virology
IS - 1
ER -