This study was designed to assess the safety, acceptability, pharmacokinetic (PK), and pharmacodynamic (PD) responses to rectal administration of tenofovir (TFV) 1% vaginally formulated gel and oral tenofovir disoproxil fumarate (TDF). This study was designed as a phase 1, randomized, two-site (United States), double-blind, placebo-controlled study of sexually abstinent men and women. Eighteen participants received a single 300-mg exposure of oral TDF and were then randomized 2:1 to receive a single and then seven daily exposures of rectal TFV or hydroxyethyl cellulose (HEC) placebo gel. Safety endpoints included clinical adverse events (AEs) and mucosal safety parameters. Blood and colonic biopsies were collected for PK analyses and ex vivo HIV-1 challenge. No serious AEs were reported. However, AEs were significantly increased with 7-day TFV gel use, most prominently with gastrointestinal AEs (p=0.002). Only 25% of participants liked the TFV gel. Likelihood of use "if somewhat protective" was ∼75% in both groups. Indices of mucosal damage showed minimal changes. Tissue TFV diphosphate (TFV-DP) C(max) 30 min after single rectal exposure was 6-10 times greater than single oral exposure; tissue TFV-DP was 5.7 times greater following 7-day versus single rectal exposure. In vivo exposure correlated with significant ex vivo tissue infectibility suppression [single-rectal: p=0.12, analysis of covariance (ANCOVA) p=0.006; 7-day rectal: p=0.02, ANCOVA p=0.005]. Tissue PK-PD was significantly correlated (p=0.002). We conclude that rectal dosing with TFV 1% gel resulted in greater TFV-DP tissue detection than oral dosing with reduced ex vivo biopsy infectibility, enabling PK-PD correlations. On the basis of increased gastrointestinal AEs, rectally applied, vaginally formulated TFV was not entirely safe or acceptable, suggesting the need for alternative rectal-specific formulations.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484811PMC
http://dx.doi.org/10.1089/aid.2012.0262DOI Listing

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Article Synopsis
  • Tenofovir-based oral pre-exposure prophylaxis has low adherence in women; however, vaginal rings could enhance user-controlled long-acting HIV prevention and possibly reduce herpes simplex virus type 2 acquisition.
  • A phase 1 trial (MTN-038) compared a 90-day vaginal ring with 1.4 grams of Tenofovir to a placebo in 49 HIV-negative participants, assessing pharmacokinetics, safety, adherence, and acceptability.
  • Results showed no significant adverse events between the two groups, with TFV concentrations initially rising but declining by day 91; adherence was reported as high, with 85% of participants in the TFV group and 81% in the placebo group claiming full adherence
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Tenofovir (TFV) is an antiviral drug used to treat the co-infections of HIV/HBV viruses. Accurate monitoring of TFV drug levels is essential for evaluating patient adherence, optimizing dosage, and assessing treatment efficacy. Herein, we propose an innovative electrochemical sensing approach by using the alkaline phosphatase (ALP) enzyme with the support of BaTiO nanoparticles.

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Tenofovir (TFV) is an adenosine nucleotide analog with activity against HIV and HSV-2. Secondary analyses of clinical trials evaluating TFV gel as pre-exposure prophylaxis (PrEP) for HIV have shown that gel formulations of TFV provide significant protection against both HIV and HSV-2 acquisition in women who had evidence of use. An alternate quick-dissolving polymeric thin film, to deliver TFV (20 and 40 mg) has been developed as a potential multipurpose technology (MPT) platform.

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