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. 2012 Oct 1;206(7):993-1001.
doi: 10.1093/infdis/jis465. Epub 2012 Jul 24.

Innate immune activation enhances hiv acquisition in women, diminishing the effectiveness of tenofovir microbicide gel

Vivek Naranbhai  1 , Salim S Abdool Karim, Marcus Altfeld, Natasha Samsunder, Raveshni Durgiah, Sengeziwe Sibeko, Quarraisha Abdool Karim, William H Carr; CAPRISA004 TRAPS team
Affiliations

Innate immune activation enhances hiv acquisition in women, diminishing the effectiveness of tenofovir microbicide gel

Vivek Naranbhai et al. J Infect Dis. .

Abstract

The antiretroviral agent, tenofovir, formulated as a vaginal microbicide gel, reduces human immunodeficiency virus (HIV) acquisition by 39% in women. This study assessed the role of preexisting immune activation in HIV acquisition in women from the CAPRISA 004 trial, to identify potential strategies to increase the effectiveness of tenofovir gel. Systemic cytokine and cellular immune mediators (platelets and natural killer [NK] cells) were assessed in women at high risk for HIV assigned to either tenofovir or placebo gel in the CAPRISA 004 trial. Notwithstanding tenofovir gel use, women who acquired HIV had significantly higher systemic innate immune activation prior to infection than women who remained uninfected. Activation of both soluble (cytokine) and cellular (NK cells) immune mediators were associated with HIV acquisition, individually or in combination. Hence, an innate immune activation suppressant could be added to tenofovir gel as a potential combination gel strategy in developing the next generation of higher efficacy antiretroviral microbicides.

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Figures

Figure 1.
Figure 1.
Heat map representation of 13 plasma cytokines measured in cases and controls. Color changes in the spectrum green to red denote increasing levels of cytokines relative to the median for all participants.
Figure 2.
Figure 2.
Cases had higher levels of natural killer (NK) cell activation in blood. A–B, Proportion of NK cells expressing (A) HLA-DR or (B) CD38 shown as representative flow cytometry plots from a case (left) in comparison to a control (right) and summary graphs of the same (below). Squares, cases; triangles, controls.
Figure 3.
Figure 3.
Cases had higher levels of spontaneous CD8 T-cell degranulation. A–B, Proportion of CD8pos T cells expressing CD107a shown as (A) representative flow cytometry plots from a case (left) in comparison to a control (right), and (B) a summary graph of the same. Squares, cases; triangles, controls.
See this image and copyright information in PMC

References

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