The coformulation of the nucleos(t)ide analogs (NA) tenofovir (TFV) disoproxil fumarate (TDF) and emtricitabine (FTC) is approved for HIV-infection treatment and prevention. Plasma TFV and FTC undergo complicated hybrid processes to form, accumulate, and retain as their active intracellular anabolites: TFV-diphosphate (TFV-DP) and FTC-triphosphate (FTC-TP). Such complexities manifest in nonline...

Empirical pharmacokinetic models are used to explain the pharmacokinetics of the antiviral drug tenofovir (TFV) and its metabolite TFV diphosphate (TFV-DP) in peripheral blood mononuclear cells. These empirical models lack the ability to explain differences between the disposition of TFV-DP in HIV-infected patients vs. healthy individuals. Such differences may lie in the mechanisms of TFV trans...

Abstract Background Obesity can affect postoperative outcomes of gastrectomy. Visceral fat area is superior to body mass index in predicting complications. However, visceral measurement time-consuming and not optimum for clinical use. Meanwhile, trunk volume (TFV) be easily measured via bioelectrical impedance analysis. Hence, the current study aimed determine ability TFV predict occurrence com...

This Phase 1, randomized, two-site (United States), double-blind, placebo-controlled study enrolled 18 sexually abstinent men and women. All received a single 300-mg dose of oral tenofovir disoproxil fumarate (TDF) and were then randomized 2:1 to receive single and then seven daily rectal exposures of vaginally-formulated tenofovir (TFV) 1% gel or a hydroxyethyl cellulose (HEC) placebo gel. Blo...

Despite the therapeutic success of tenofovir (TFV) for treatment of HIV-1 infection, numerous cases of nephrotoxicity have been reported. Mitochondrial toxicity has been purported as the major target of TFV-associated renal tubulopathy but the underlying molecular mechanism remains unclear. In this report, we use metabolomics and proteomics with HK-2 cells and animal models to dissect the molec...

Tenofovir (TFV) undergoes renal elimination by a combination of glomerular filtration and active tubular secretion. While transporter-mediated uptake of TFV from the blood into proximal-tubule cells has been well characterized, comparatively little is known about the efflux system responsible for transporting TFV into the lumen during active tubular secretion. Therefore, members of the ATP-bind...

Tenofovir (TFV), an acyclic nucleoside phosphonate analogue of 2′deoxyadenosine, remains a first-line choice for the treatment of HIV infections under its prodrug form (i.e. tenofovir disoproxil fumarate, TDF). During the last decade, the use of TFV in pre-exposure prophylaxis (PrP) was first investigated as a vaginal microbicide gel (Mayer et al., 2006). More recently, rectal microbicide prepa...

BACKGROUND Tenofovir (TFV) gel is being evaluated as a microbicide with pericoital and daily regimens. To inhibit viral replication locally, an adequate concentration in the genital tract is critical. METHODS AND FINDINGS Forty-nine participants entered a two-phase study: single-dose (SD) and multi-dose (MD), were randomized to collection of genital tract samples (endocervical cells [ECC], ce...

Disruption of the epithelium in the female reproductive tract (FRT) is hypothesized to increase HIV infection risk by interfering with barrier protection and facilitating HIV-target cell recruitment. Here we determined whether Tenofovir (TFV), used vaginally in HIV prevention trials, and Tenofovir alafenamide (TAF), an improved prodrug of TFV, interfere with wound healing in the human FRT. TFV ...

The objective of this analysis was to develop and qualify a population pharmacokinetic model describing plasma tenofovir (TFV) concentrations and tenofovir-diphosphate (TFV-DP) concentrations in peripheral blood mononuclear cell (PBMC) in healthy women volunteers from the MTN-001 clinical trial, an open label 3-way crossover study of oral tenofovir disoproxil fumarate 300 mg tablet, TFV 1% vagi...