Background:  One of the major potential models for HIV-1 entry into the brain is based on the “Trojan Horse” hypothesis that virally infected monocytes/macrophages and possibly CD4⁺ T cells are a major source of virus in the brain of infected individuals.

Methods:  For analysis we used transmigration assays across primary human cells blood–brain barrier model, Western blotting, and gene microarray technology.

Results:  Herein, we demonstrate that statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors significantly control enhanced transmigration of HIV-1-infected primary monocytes and CD4⁺ T cells through a model basement membrane constituted of Matrigel and a cellular in vitro blood–brain barrier model comprised of primary human brain microvascular endothelial cells and astrocytes. The enhanced transmigration of HIV-1-infected monocytes was associated with up-regulation of matrix metalloproteinases (MMP) 2 and 9, whereas HIV-1-infected T cells’ elevated transmigration was associated with down-modulation of TIMP-2 and enhanced expression of MMP-17, a membrane type MMP. Statins normalized elevated levels of MMP in both monocytes and CD4⁺ T cells, as well as suppressed enhanced transmigration associated with HIV-1 infection.

Conclusions:  Thus, prevention of enhanced transmigration of HIV-1-infected cells with statins could potentially be of benefit by 2 mechanisms:  limiting AIDS-related neuropathologies, and controlling establishment of HIV-1 reservoirs in the brains of infected individuals.

Keywords: Transmigration; Statins; AIDS Dementia