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Clinical Trial
. 2013 Jul 1;63(3):294-8.
doi: 10.1097/QAI.0b013e31828e604b.

Neither microbial translocation nor TLR responsiveness are likely explanations for preexisting immune activation in women who subsequently acquired HIV in CAPRISA 004

Vivek Naranbhai  1 , Natasha Samsunder, Netanya G Sandler, Annalys Roque, Quarraisha Abdool Karim, Thumbi Ndungʼu, William H Carr, Marcus Altfeld, Daniel C Douek, Salim S Abdool Karim; CAPRISA 004 Trial Team
Affiliations
Clinical Trial

Neither microbial translocation nor TLR responsiveness are likely explanations for preexisting immune activation in women who subsequently acquired HIV in CAPRISA 004

Vivek Naranbhai et al. J Acquir Immune Defic Syndr. .

Abstract

Innate immune activation was a strong predictor of HIV acquisition in women at risk for HIV in CAPRISA 004. Identifying the cause(s) of activation could enable targeted prevention interventions. In this study, plasma concentrations of lipopolysaccharide, soluble CD14, and intestinal fatty acid-binding protein did not differ between subjects who did or did not subsequently acquire HIV nor were these levels correlated with plasma cytokines or natural killer cell activation. There was no difference between HIV acquirers and non-acquirers in the chemokine and cytokine responses of peripheral blood mononuclear cells stimulated with TLR2, 4, or 7/8 agonists. Further studies are required.

Trial registration: ClinicalTrials.gov NCT00441298.

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Figures

Figure 1
Figure 1
Plasma levels of LPS (A), sCD14 (B) and I-FABP (C) do not differ between women who acquired HIV samples pre-infection (grey squares) and women who remained HIV uninfected (black triangles). Lines demarcate the median and interquartile range. p-value from Mann-Whitney test.
Figure 2
Figure 2
PBMC from HIV acquirers (black) and HIV non-acquirers (grey) exhibit a similar fold change (log10) in the secretion of chemokines and cytokines after stimulation with a TLR7/8 agonist (aldrithiol inactivated virus, AT-2 HIV), TLR2 agonist (heat-killed Listeria monocytgenes, HKLM) or a TLR4 agonist lipopolysaccharide, LPS) relative to media alone. 1 × 106 PBMC were stimulated with the agonist shown overnight and cytokines/chemokines measured by Luminex in duplicate. Data are shown as box and whiskers to 5th and 95th percentile. Adjusted p-values are not shown as none achieved significance although the nominal p-value for the comparison of IFN-secretion after AT-2 stimulation in HIV acquirers and non-acquirers was p=0.05 (Bonferroni-adjusted p<0.0013 for significance).
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