PREP Human
Description
Definition and Purpose of PrEP
Pre-exposure prophylaxis (PrEP) is a biomedical HIV prevention strategy involving the use of antiretroviral (ARV) drugs by HIV-negative individuals to reduce the risk of acquiring HIV. PrEP is not a single compound but a regimen combining two ARV agents: tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC). These are nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) that block HIV replication at the stage of viral DNA synthesis .
Approved PrEP Formulations
Two FDA-approved oral formulations dominate clinical use:
Notes:
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TAF (tenofovir alafenamide) has improved renal and bone safety compared to TDF .
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Long-acting injectable cabotegravir (Apretude®) is administered intramuscularly and shows higher efficacy in clinical trials .
Mechanism of Action
PrEP disrupts the HIV lifecycle through two mechanisms:
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Emtricitabine: Competes with endogenous cytosine nucleotides, terminating viral DNA chain elongation.
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Tenofovir: Inhibits HIV reverse transcriptase by mimicking adenosine monophosphate, causing chain termination .
Key pharmacokinetic properties:
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Plasma half-life: ~10 hours (TDF/FTC), requiring daily adherence for optimal protection .
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Tissue penetration: High concentrations in rectal, vaginal, and penile tissues .
Landmark Studies:
Real-world effectiveness:
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Meta-analysis of 68 studies shows 86% effectiveness with daily use .
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On-demand ("2-1-1") dosing for gbMSM: 86% efficacy when taken pre/post sex .
Eligible Populations:
Contraindications:
Emerging Research and Innovations
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Lenacapavir: A novel capsid inhibitor administered every 6 months, currently in Phase 3 trials for PrEP. Early data show 100% efficacy in preventing HIV acquisition .
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Human pangenome integration: Genomic diversity studies (e.g., EMBL's 2024 pangenome project) aim to optimize PrEP efficacy across global populations by identifying genetic factors influencing drug metabolism .
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Psychosocial barriers: Structural inequities (e.g., homelessness, incarceration) reduce PrEP uptake by 45–75% in marginalized groups .
Global Guidelines
Future Directions
Product Specs
Product Science Overview
Prolyl Endopeptidase is a large enzyme with a molecular mass of approximately 81 kDa . It cleaves peptide bonds at the C-terminal side of proline residues within peptides that are up to approximately 30 amino acids long . The enzyme’s activity is confined to oligopeptides of less than 10 kDa and requires the trans-configuration of the peptide bond preceding proline .
The enzyme’s structure includes a distinct beta-propeller region that acts as a gating filter mechanism, allowing only short protein residues to enter the active site . This specificity enables Prolyl Endopeptidase to hydrolyze a variety of biologically active peptides such as bradykinin, substance P, neurotensin, and vasopressin .
Prolyl Endopeptidase is involved in several critical biological processes, including the maturation and degradation of peptide hormones and neuropeptides . Some of the key peptides hydrolyzed by this enzyme include:
- Bradykinin: A peptide that causes blood vessels to dilate, leading to a drop in blood pressure.
- Substance P: A neuropeptide involved in the transmission of pain and other sensory signals.
- Neurotensin: A peptide that modulates dopamine signaling and has various effects on the central nervous system.
- Vasopressin: A hormone that regulates water retention in the body .
Recombinant Human Prolyl Endopeptidase is produced using baculovirus expression systems in insect cells (Spodoptera frugiperda, Sf 21) . The recombinant enzyme is typically tagged with a 6-His tag for purification purposes and is supplied as a carrier-free formulation to avoid interference from other proteins .
Recombinant Prolyl Endopeptidase is widely used in biochemical research to study its role in peptide hormone regulation and neuropeptide degradation. It is also utilized in drug development to explore potential therapeutic targets for conditions related to peptide hormone imbalances and neurodegenerative diseases .
