Trial reportPloS one2011
First phase 1 double-blind, placebo-controlled, randomized rectal microbicide trial using UC781 gel with a novel index of ex vivo efficacy.
Trial report in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 51 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 Phase 1 Randomized, Blinded, Placebo-Controlled Safety and Acceptability Study of the UC-781 Vaginal Microbicide Gel Formulation Applied Rectally in HIV-1 Seronegative Adults
The Time to Protection and Adherence Requirements of Raltegravir With or Without Lamivudine in Protection From HIV Infection
Who cites it
51 citing papers in PubMed, 83 citations in OpenAlex.
- Rapid Collection of Human Rectal Secretions Using OriCol Devices Is Suitable for Measurement of Mucosal Ig without Blood Contamination.Journal of immunology (Baltimore, Md. : 1950) · 2020Trial
- Analytical Advances in the Ex Vivo Challenge Efficacy Assay.AIDS research and human retroviruses · 2017Trial
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- Mucosal effects of tenofovir 1% gel.eLife · 2015Trial
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- Isoosmolar enemas demonstrate preferential gastrointestinal distribution, safety, and acceptability compared with hyperosmolar and hypoosmolar enemas as a potential delivery vehicle for rectal microbicides.AIDS research and human retroviruses · 2013Trial
- A phase 1 randomized, double blind, placebo controlled rectal safety and acceptability study of tenofovir 1% gel (MTN-007).PloS one · 2013Trial
- RMP-02/MTN-006: A phase 1 rectal safety, acceptability, pharmacokinetic, and pharmacodynamic study of tenofovir 1% gel compared with oral tenofovir disoproxil fumarate.AIDS research and human retroviruses · 2012Trial
- UC781 microbicide gel retains anti-HIV activity in cervicovaginal lavage fluids collected following twice-daily vaginal application.Antimicrobial agents and chemotherapy · 2012Trial
- Mucosal Responses to Zika Virus Infection in Cynomolgus Macaques.Pathogens (Basel, Switzerland) · 2022Article
- Pre-Clinical Evaluation of Tenofovir and Tenofovir Alafenamide for HIV-1 Pre-Exposure Prophylaxis in Foreskin Tissue.Pharmaceutics · 2022Article
- Ex Vivo HIV Infection Model of Cervico-Vaginal and Rectal Tissue.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Human Vault Nanoparticle Targeted Delivery of Antiretroviral Drugs to Inhibit Human Immunodeficiency Virus Type 1 Infection.Bioconjugate chemistry · 2019Article
- The Use of Droplet Digital PCR to Quantify HIV-1 Replication in the Colorectal Explant Model.AIDS research and human retroviruses · 2019Article
- 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
- Impact of the griffithsin anti-HIV microbicide and placebo gels on the rectal mucosal proteome and microbiome in non-human primates.Scientific reports · 2018Article
- Human Semen or Seminal Plasma Does Not Enhance HIV-1AIDS research and human retroviruses · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 5 institutions in 1 country.
Funding
Abstract
objectivesSuccessful control of the HIV/AIDS pandemic requires reduction of HIV-1 transmission at sexually-exposed mucosae. No prevention studies of the higher-risk rectal compartment exist. We report the first-in-field Phase 1 trial of a rectally-applied, vaginally-formulated microbicide gel with the RT-inhibitor UC781 measuring clinical and mucosal safety, acceptability and plasma drug levels. A first-in-Phase 1 assessment of preliminary pharmacodynamics was included by measuring changes in ex vivo HIV-1 suppression in rectal biopsy tissue after exposure to product in vivo.
methodsHIV-1 seronegative, sexually-abstinent men and women (N = 36) were randomized in a double-blind, placebo-controlled trial comparing UC781 gel at two concentrations (0.1%, 0.25%) with placebo gel (1∶1∶1). Baseline, single-dose exposure and a separate, 7-day at-home dosing were assessed. Safety and acceptability were primary endpoints. Changes in colorectal mucosal markers and UC781 plasma drug levels were secondary endpoints; ex vivo biopsy infectibility was an ancillary endpoint.
resultsAll 36 subjects enrolled completed the 7-14 week trial (100% retention) including 3 flexible sigmoidoscopies, each with 28 biopsies (14 at 10 cm; 14 at 30 cm). There were 81 Grade 1 adverse events (AEs) and 8 Grade 2; no Grade 3, 4 or procedure-related AEs were reported. Acceptability was high, including likelihood of future use. No changes in mucosal immunoinflammatory markers were identified. Plasma levels of UC781 were not detected. Ex vivo infection of biopsies using two titers of HIV-1(BaL) showed marked suppression of p24 in tissues exposed in vivo to 0.25% UC781; strong trends of suppression were seen with the lower 0.1% UC781 concentration.
conclusionsSingle and 7-day topical rectal exposure to both concentrations of UC781 were safe with no significant AEs, high acceptability, no detected plasma drug levels and no significant mucosal changes. Ex vivo biopsy infections demonstrated marked suppression of HIV infectibility, identifying a potential early biomarker of efficacy. (Registered at ClinicalTrials.gov; #NCT00408538).
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What OpenQuestion holds
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.