Trial reportPloS one2014
Correlation between compartmental tenofovir concentrations and an ex vivo rectal biopsy model of tissue infectibility in the RMP-02/MTN-006 phase 1 study.
Trial report in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00984971 (A Two-site, Phase 1, Partially-blinded, Placebo-controlled Safety, Acceptability and Pharmacokinetic Trial of Topical, Vaginally-formulated Tenofovir 1% Gel Applied Rectally Compared With Oral 300 mg Tenofovir Disoproxil Fumarate in HIV-1 Seronegative Adults), which is not on this map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Two-site, Phase 1, Partially-blinded, Placebo-controlled Safety, Acceptability and Pharmacokinetic Trial of Topical, Vaginally-formulated Tenofovir 1% Gel Applied Rectally Compared With Oral 300 mg Tenofovir Disoproxil Fumarate in HIV-1 Seronegative Adults
Who cites it
23 citing papers in PubMed, 30 citations in OpenAlex.
- Pharmacokinetic/pharmacodynamic investigation of raltegravir with or without lamivudine in the context of HIV-1 pre-exposure prophylaxis (PrEP).The Journal of antimicrobial chemotherapy · 2021Trial
- A Mechanistic In Vivo/Ex Vivo Pharmacokinetic-Pharmacodynamic Model of Tenofovir for HIV Prevention.CPT: pharmacometrics & systems pharmacology · 2021Trial
- Analytical Advances in the Ex Vivo Challenge Efficacy Assay.AIDS research and human retroviruses · 2017Trial
- Trial
- Comparison of Follicular and Luteal Phase Mucosal Markers of HIV Susceptibility in Healthy Women.AIDS research and human retroviruses · 2016Trial
- Trial
- Mucosal Responses to Zika Virus Infection in Cynomolgus Macaques.Pathogens (Basel, Switzerland) · 2022Article
- TheiScience · 2022Article
- Pre-Clinical Evaluation of Tenofovir and Tenofovir Alafenamide for HIV-1 Pre-Exposure Prophylaxis in Foreskin Tissue.Pharmaceutics · 2022Article
- Ex Vivo Evaluation of Mucosal Responses to Vaccination with ALVAC and AIDSVAX of Non-Human Primates.Vaccines · 2022Article
- Pre-clinical evaluation of antiproteases as potential candidates for HIV-1 pre-exposure prophylaxis.Frontiers in reproductive health · 2022Article
- Naturally Occurring Mutations to Muscle-Type Creatine Kinase Impact Its Canonical and Pharmacological Activities in a Substrate-Dependent Manner In Vitro.Molecular pharmacology · 2021Article
- Importance of structure-based studies for the design of a novel HIV-1 inhibitor peptide.Scientific reports · 2020Article
- The Pre-clinical Toolbox of Pharmacokinetics and Pharmacodynamics:Frontiers in pharmacology · 2019Review
- Comparative Assessment of Small and Large Intestine Biopsies for Ex Vivo HIV-1 Pathogenesis Studies.AIDS research and human retroviruses · 2018Article
- Heterogeneity of HIV-1 Replication in Ectocervical and Vaginal Tissue Ex Vivo.AIDS research and human retroviruses · 2018Article
- Comparison of tenofovir plasma and tissue exposure using a population pharmacokinetic model and bootstrap: a simulation study from observed data.Journal of pharmacokinetics and pharmacodynamics · 2017Article
- Comparison of Mucosal Markers of Human Immunodeficiency Virus Susceptibility in Healthy Premenopausal Versus Postmenopausal Women.AIDS research and human retroviruses · 2017Article
- The Safety of Multiple Flexible Sigmoidoscopies with Mucosal Biopsies in Healthy Clinical Trial Participants.AIDS research and human retroviruses · 2017Article
- Oligonucleotide-Lipid Conjugates Forming G-Quadruplex Structures Are Potent and Pangenotypic Hepatitis C Virus Entry InhibitorsAntimicrobial agents and chemotherapy · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 6 institutions in 1 country.
Funding
Abstract
objectivesThis study was designed to assess the dose-response relationship between tissue, blood, vaginal and rectal compartment concentrations of tenofovir (TFV) and tenofovir diphosphate (TFVdp) and ex vivo rectal HIV suppression following oral tenofovir disoproxil fumarate (TDF) and rectal administration of TFV 1% vaginally-formulated gel.
designPhase 1, randomized, two-site (US), double-blind, placebo-controlled study of sexually-abstinent males and females.
methodsEighteen participants received a single 300 mg exposure of oral TDF and were then randomized 2∶1 to receive a single then seven-daily rectal exposures of TFV 1% gel (40 mg TFV per 4 ml gel application) or hydroxyethyl-cellulose (HEC) placebo gel. Blood and rectal biopsies were collected for pharmacokinetic TDF and TFVdp analyses and ex vivo HIV-1 challenge.
resultsThere was a significant fit for the TFVdp dose-response model for rectal tissue (p = 0.0004), CD4+MMC (p<0.0001), CD4-MMC (p<0.0001), and TotalMMC (p<0.0001) compartments with r2 ranging 0.36-0.64. Higher concentrations of TFVdp corresponded with lower p24, consistent with drug-mediated virus suppression. The single oral treatment failed to provide adequate compartment drug exposure to reach the EC50 of rectal tissue TFVdp predicted to be necessary to suppress HIV in rectal tissue. The EC50 for CD4+MMC was within the single topical treatment range, providing evidence that a 1% topical, vaginally-formulated TFV gel provided in-vivo doses predicted to provide for 50% efficacy in the ex vivo assay. The 7-daily topical TFV gel treatment provided TFVdp concentrations that reached EC90 biopsy efficacy for CD4-MMC, CD4+MMC and TotalMMC compartments.
conclusionThe TFVdp MMC compartment (CD4+, CD4- and Total) provided the best surrogate for biopsy infectibility and the 7-daily topical TFV gel treatment provided the strongest PK profile for HIV suppression. ClinicalTrials.gov NCT00984971.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.