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

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.