The Effects of Human Immunodeficiency Virus Infection on the Expression of the Drug Efflux Proteins P-glycoprotein and Breast Cancer Resistance Protein in a Human Intestine Model

Document Type

Article

Publication Title

Journal of Pharmacy and Pharmacology

Abstract

Objectives:

In human immunodeficiency virus (HIV) infection, decreased penetration of antiretroviral drugs is postulated to contribute to HIV persistence within lymphoid-rich regions of the gastrointestinal (GI) tract. However, mechanistic explanations for this phenomenon remain unclear. Specifically, investigations of HIV effects on drug efflux proteins within intestinal models are minimal.

Methods:

Using an in-vitro co-culture model of the GI tract, the effects of HIV infection on drug efflux proteins, P-glycoprotein and breast cancer resistance protein (BCRP) were evaluated. The influence of the HIV-1 protein, Tat, and oxidative stress on P-glycoprotein and BCRP was also evaluated.

Key Findings:

P-glycoprotein expression demonstrated an HIV-induced upregulation in Caco-2 cells over time for cells grown in co-culture with resting lymphocytes. BCRP overall expression increased with HIV exposure in activated primary human lymphocytes co-cultured with Caco-2 cells. Tat treatment resulted in no significant alterations in P-glycoprotein (43% increase), BCRP expression, or oxidative stress.

Conclusions:

HIV exposure within an in-vitro intestinal model resulted in increases in P-glycoprotein and BCRP in a cell-specific manner. Additionally, observed changes were not mediated by Tat. Collectively, these results suggest that alterations in BCRP and P-glycoprotein may contribute, in part, to decreased antiretroviral concentrations within the gut-associated lymphoid tissue of the GI tract in HIV infection.

DOI

10.1111/jphp.12329

Publication Date

2-2015

Keywords

breast cancer resistance protein, HIV, HIV-1 Tat, P-glycoprotein

ISSN

2042-7158

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