FR AX 0103
Association between genital tract inflammation during acute HIV-1 infection and HIV disease progression
Presented by Lindi Roberts (South Africa).
L. Roberts1, J.-A. Passmore1,2, C. Williamson1,3, F. Little1, L. Bebell3,4, K. Mlisana3, F. van Loggerenberg3, G. Walzl5, Q. Abdool Karim3,4, S. Abdool Karim3,4
1University of Cape Town, Cape Town, South Africa, 2National Health Laboratory Services, Cape Town, South Africa, 3Centre for AIDS Programme of Research (CAPRISA), Durban, South Africa, 4Columbia University, New York, United States, 5University of Stellenbosch, Cape Town, South Africa
Background: Early immune events in the female genital tract have been shown to influence systemic spread of SIV in primate models. We have previously shown in humans that inflammation in the genital tract during acute HIV-1 infection is associated with lower CD4 counts in blood, suggesting that local mucosal factors may influence clinical HIV disease progression. The aim of this study was to investigate the relationship between genital tract cytokine levels during acute HIV infection and the subsequent rate of disease progression.
Methods: The concentrations of 32 cytokines in cervicovaginal lavage (CVL) samples from women with acute HIV-1 infection (n=37) from the CAPRISA acute HIV infection cohort in Durban, South Africa were measured using Luminex and ELISA. Cytokine concentrations during acute infection were compared to matched pre-infection samples (n=18). Associations between cytokine concentrations and markers of HIV disease progression (CD4 count and viral load set-points at 12 months post-infection) were determined by regression analysis.
Results: Cytokine concentrations in CVL from acutely HIV-infected women included in this study did not differ significantly from concentrations measured in their pre-infection CVLs. However, 12/32 cytokines measured were found to be significantly correlated pre- and post-HIV-infection. Elevated IL-1β, IL-8, IL-12(p70), IL-15, GM-CSF, TNF-α and IL-10, were each associated with higher viral load set-point 12 months post-infection, while the same cytokines and additionally IL-6 and RANTES were associated with lower CD4 counts. Higher concentrations of IFN-γ, however, were associated with higher CD4 counts. Following adjustment for multiple comparisons, GM-CSF remained significantly associated with CD4 counts 12 months post-infection. The pro-inflammatory cytokine cluster [IL-1α, IL-1β, IL-6, IL-12(p70), TNF-α], determined by factor analysis, was significantly associated with both higher viral load and lower CD4 count set-points.
Conclusions: Genital tract inflammatory cytokine responses during acute HIV-1 infection were associated with more rapid HIV disease progression, while IFN-γ was associated with better prognosis.
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