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Review
. 2017 Jun;33(6):513-523.
doi: 10.1089/AID.2016.0253. Epub 2017 May 16.

HIV Persistence in Gut-Associated Lymphoid Tissues: Pharmacological Challenges and Opportunities

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Free PMC article
Review

HIV Persistence in Gut-Associated Lymphoid Tissues: Pharmacological Challenges and Opportunities

Corbin G Thompson et al. AIDS Res Hum Retroviruses. .
Free PMC article

Abstract

An increasing amount of evidence suggests that HIV replication persists in gut-associated lymphoid tissues (GALT), despite treatment with combination antiretroviral therapy (cART). Residual replication in this compartment may propagate infection at other sites in the body and contribute to sustained immune dysregulation and delayed immune recovery. Therefore, it is important to focus efforts on eliminating residual replication at this site. There are several challenges to accomplishing this goal, including low antiretroviral (ARV) exposure at specific tissue locations within GALT, which might be overcome by using the tools of clinical pharmacology. Here, we summarize the evidence for GALT as a site of residual HIV replication, highlight the consequences of persistent infection in tissues, identify current pharmacologic knowledge of drug exposure in GALT, define the challenges that hinder eradication from this site, and propose several avenues for pharmacologic intervention.

Keywords: GALT; antiretrovirals; imaging; persistence; pharmacology; reservoirs.

Conflict of interest statement

No competing financial interests exist.

Figures

<b>FIG. 1.</b>
FIG. 1.
Factors influencing antiretroviral disposition and efficacy in GALT. Solubilized drugs (white, gray, and black circles) can penetrate into the intestinal tissue from peripheral blood supply or directly from the intestinal lumen. Penetration arising from the blood is dependent on the amount of local perfusion as well as on pharmacokinetic properties of the drug, that is, drug bound to plasma protein (shown within blood vessel) cannot enter the tissue. Penetration from the gut lumen is dependent on physicochemical properties of each drug as well as on the affinity for drug efflux (white, black) or uptake (gray) transporters on the surface of epithelial cells. GALT-specific exposure is also dependent on local blood perfusion and drug transporter expression on the surface of lymphocytes. GALT, gut-associated lymphoid tissues; PK, pharmacokinetic.

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