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Antivir Ther. 2019;24(1):45-50. doi: 10.3851/IMP3277.

Differential extracellular, but similar intracellular, disposition of two tenofovir formulations in the male genital tract.

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UNC Eshelman School of Pharmacy, Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Present address: SK Life Science, Inc., Fairlawn, NJ, USA.
UNC School of Medicine, Department of Internal Medicine, Division of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Present address: Merck CO, Philadelphia, PA, USA.
UNC School of Medicine, Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.



The male genital tract (MGT) is a viral sanctuary and likely HIV reservoir; understanding MGT pharmacokinetics (PK) of antiretrovirals (ARVs) used for curative strategies is critical to eradication and cure. Tenofovir alafenamide (TAF) is a tenofovir (TFV) formulation designed to maximize efficacy/minimize toxicity with unknown MGT PK.


HIV-positive and HIV-negative men receiving TFV-based regimens provided six paired blood plasma (BP) and semen samples. Extracellular (TFV, TAF, emtricitabine [FTC]) drug concentrations in BP and seminal plasma (SP), and intracellular metabolite (IM) and endogenous nucleotide (EN) concentrations were measured in peripheral blood mononuclear cells (PBMCs) and seminal mononuclear cells (SMCs). Exposure ratios for SP:BP, SMC:PBMC and IM:EN were calculated from PK parameters generated by noncompartmental analysis. HIV viral load was measured in BP and SP.


Sixteen HIV-positive (n=8, TDF/FTC; n=8, TAF/FTC) and eight HIV-negative (TDF/FTC) men provided samples. Median TFV SP:BP ratios differed between TDF and TAF (1.5 versus 7.4), due to lower TFV BP concentrations with TAF coupled with TFV SP concentrations similar to TDF.


BP ratios were approximately 3. SMC concentrations of IMs and ENs were a fraction of PBMC concentrations (1-22%), though IM:EN ratios exceed a suggested protective threshold.


TAF SP PK was unexpected. IM SMC concentrations were low relative to PBMC, as were EN concentrations, suggesting differences in cell phenotype and lineage in the MGT; these differences in phenotype and pharmacology may have an impact on selecting and dosing ARVs used in cure strategies.


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