Oral Combinational Antiretroviral Treatment in HIV-1 Infected Humanized Mice

Wenli Mu; Anjie Zhen; Mayra A. Carrillo; Valerie Rezek; Heather Martin; Miguel Lizarraga; Scott Kitchen

doi:10.3791/63696

Traitement antirétroviral combiné oral chez des souris humanisées infectées par le VIH-1

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Immunology and Infection

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JoVE Journal Immunology and Infection

Oral Combinational Antiretroviral Treatment in HIV-1 Infected Humanized Mice

Traitement antirétroviral combiné oral chez des souris humanisées infectées par le VIH-1

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06:07 min

October 6, 2022

DOI: 10.3791/63696-v

Wenli Mu¹, Anjie Zhen¹, Mayra A. Carrillo¹, Valerie Rezek¹, Heather Martin¹, Miguel Lizarraga¹, Scott Kitchen¹

¹Division of Hematology and Oncology, David Geffen School of Medicine,University of California, Los Angeles

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Overview

This protocol describes a novel method to deliver oral combination antiretroviral drugs that successfully suppresses HIV RNA replication in humanized mice. The method improves upon previous delivery techniques by enhancing safety and reducing stress associated with daily injections.

Key Study Components

Area of Science

Neuroscience
Virology
Pharmacology

Background

HIV-1 RNA replication poses significant challenges in treatment.
Current methods often involve stressful daily injections.
Oral delivery methods could improve patient compliance.
Humanized mice serve as a valuable model for studying HIV treatments.

Purpose of Study

To develop a safer and more effective oral delivery method for ART.
To reduce stress in animal models during drug administration.
To provide a preclinical proof-of-concept for future HIV cure treatments.

Methods Used

Preparation of combination antiretroviral drugs (cART) in sterile conditions.
Weighing individual drugs for precise formulation.
Using sterile food cups for drug delivery to mice.
Demonstration of the procedure by lab personnel.

Main Results

The novel oral ART method effectively suppresses HIV RNA replication.
Reduced animal stress compared to injection methods.
Improved safety and ease of preparation for drug administration.
Potential for application in chronic HIV-infected individuals.

Conclusions

The oral delivery method shows promise for future HIV treatment studies.
It may lead to better compliance in chronic treatment scenarios.
Further research is needed to validate its effectiveness in humans.

Frequently Asked Questions

What is the significance of this study?

This study presents a novel oral method for delivering ART, which could enhance treatment compliance and reduce stress in animal models.

How does the oral delivery method compare to injections?

The oral method is safer, easier to prepare, and less stressful for the animals compared to daily injections.

What are the key components of the combination antiretroviral drugs used?

The study uses FTC, TDF, and RAL or ELV in the formulation of cART.

Who conducted the demonstration of the procedure?

Valerie Rezak, a lab manager and technician, demonstrated the procedure.

What are the implications for future HIV treatments?

This method could provide a preclinical proof-of-concept for developing novel cure treatments that mimic chronic HIV infection drug delivery.

Ce protocole décrit une nouvelle méthode pour administrer des médicaments antirétroviraux combinés oraux qui suppriment avec succès la réplication de l’ARN du VIH-1 chez des souris humanisées.

Ce protocole décrit une nouvelle méthode d’administration de médicaments antirétroviraux combinés oraux, ou TAR, qui supprime avec succès la réplication de l’ARN du VIH chez des souris humanisées. La nouvelle méthode orale de TAR surpasse les tentatives d’accouchement précédentes en raison de son innocuité, de sa facilité de préparation et d’administration et de la réduction du stress des animaux résultant d’une injection quotidienne. La méthode d’administration orale proposée pour supprimer la réplication de l’ARN du VIH chez les souris humanisées sera très utile pour les études précliniques de preuve de concept visant à mettre au point de nouveaux traitements curatifs qui imitent étroitement l’administration du médicament chez les personnes infectées par le VIH chronique.

La démonstration de la procédure sera Valerie Rezak, gestionnaire de laboratoire et technicienne de notre laboratoire. Commencez par peser les médicaments individuels. Fabriquez 10 gobelets alimentaires avec cART à l’aide de racleurs à cellules stériles pour peser 250 milligrammes de FTC, 375 milligrammes de TDF et 500 milligrammes de RAL ou d’ELV dans des tubes centrifugés individuels stériles de 50 millilitres dans une armoire de biosécurité.

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