Pharmacokinetics of antiretrovirals in mucosal tissue

Abstract

Introduction: In the absence of an HIV vaccine or cure, antiretroviral (ARV)-based prevention strategies are being investigated to reduce HIV incidence. These prevention strategies depend on achieving effective drug concentrations at the site of HIV exposure, which is most commonly the mucosal tissue of the lower gastrointestinal tract and the female genital tract.

Areas covered: This article collates all known data regarding drug exposure in these vulnerable mucosal tissues and reviews important mechanisms of ARV drug distribution. Research papers and abstracts describing ARV pharmacokinetics (PK) in the female genital tract and lower gastrointestinal mucosal tissues available in MEDLINE® or presented at scientific conferences prior to December 2014 are reviewed in detail. Important influences on ARV mucosal tissue distribution, including protein binding, active drug transport and endogenous hormones are also reviewed.

Expert opinion: ARVs exhibit highly variable PK in mucosal tissues. In general, ARV exposure is higher in the lower gastrointestinal tract compared with the female genital tract, but concentrations required for protective efficacy are largely unknown. The expected site of HIV exposure represents an important consideration when designing and optimizing ARV-based prevention strategies.

Keywords:

• antiretroviral
• HIV prevention
• mucosal tissue
• pharmacokinetics

Declaration of interest

This work was supported by the Centers for AIDS Research [grant number CFAR P30 AI50410], the National Institute for Allergy and Infectious Diseases [grant number R01 AI111891 and U19 AI09611] and the National Institute of General Medical Sciences [grant number T32 GM086330]. N Srinivas is supported by the Royster Society of Fellows. The content is solely the responsibility of the authors and does not necessarily represent the official views of the supporting agencies listed above. A Kashuba and her laboratory are part of the study teams for CAPRISA 004 and 008, FACTS 001, MTN 006, HPTN 066, FEM-PrEP and CONRAD 113, 114, 117 and 118.

Notes

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