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Pharmacokinetics of Antiretrovirals in Genital Secretions and Anatomic Sites of HIV Transmission: Implications for HIV Prevention

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Abstract

The incidence of HIV remains alarmingly high in many parts of the world. Prophylactic use of antiretrovirals, capable of concentrating in the anatomical sites of transmission, may reduce the risk of infection after an unprotected sexual exposure. To date, orally and topically administered antiretrovirals have exhibited variable success in preventing HIV transmission in large-scale clinical trials. Antiretroviral mucosal pharmacokinetics may help explain the outcomes of these investigations. Penetration and accumulation of antiretrovirals into sites of transmission can influence dosing strategies and pre-exposure prophylaxis clinical trial design. Antiretroviral tissue distribution varies widely within and between drug classes, attributed in part to their physicochemical properties and tissue-specific drug transporter expression. Nucleoside(-tide) reverse transcriptase inhibitors, the CCR5 antagonist maraviroc, and the integrase inhibitor raltegravir demonstrate the highest penetration into the male and female reproductive tracts and colorectal tissue relative to blood. This review describes antiretroviral exposure in anatomic sites of transmission, and places these findings in context with the prevention of HIV and the efficacy of pre-exposure prophylactic strategies.

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Acknowledgments

This work was supported by the UNC Center for AIDS Research [grant number CFAR P30 AI50410] and the National Institutes of Allergy and Infectious Diseases [grant number U01 AU095031]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the supporting agencies listed above. Angela Kashuba has received honoraria from Merck & Co. and her spouse is employed by GlaxoSmithKline. Christine Trezza has no conflicts of interest to declare.

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  1. Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, 3318 Kerr Hall, CB# 7569, Chapel Hill, NC, 27599-7569, USA

    Christine R. Trezza & Angela D. M. Kashuba

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Correspondence to Angela D. M. Kashuba.

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Trezza, C.R., Kashuba, A.D.M. Pharmacokinetics of Antiretrovirals in Genital Secretions and Anatomic Sites of HIV Transmission: Implications for HIV Prevention. Clin Pharmacokinet 53, 611–624 (2014). https://doi.org/10.1007/s40262-014-0148-z

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