An Efficient Humanized Mouse Model for Oral Anti-Retroviral Administration

Area of Science:

• * Immunology and Virology
• * Pharmacology and Toxicology

Background:

• * Anti-retrovirals (ARVs) have improved life expectancy for people living with HIV (PLWH).
• * Long-term ARV use is linked to toxic effects and co-morbidities like heart disease, bone loss, and HIV-associated neurocognitive disorders (HAND).
• * Established mouse models for studying ARV effects on viral suppression, toxicity, and latency are limited.

Purpose of the Study:

• * To develop and validate an effective mouse model for studying anti-retroviral therapy (ART) in HIV.
• * To assess ARV drug penetration and viral load dynamics in various tissues and plasma.
• * To investigate ARV effects relevant to HIV co-morbidities, including HAND.

Main Methods:

• * Utilized immune-compromised mice reconstituted with human peripheral blood mononuclear cells (PBMCs) infected with HIV.
• * Administered combination ARV regimens (Atripla and Triumeq) daily via mouse chow.
• * Measured HIV-infected cell trafficking, ARV penetration in organs and plasma, and viral load reduction.

Main Results:

• * Demonstrated successful HIV-infected human cell trafficking to secondary lymphoid organs and other tissues.
• * Confirmed ARV penetration and significant reduction in HIV viral load in plasma and organs of treated mice compared to controls.
• * Established an effective and affordable mouse model for ARV research.

Conclusions:

• * The developed mouse model is a viable tool for studying ARV efficacy and tissue distribution.
• * This model can be used to investigate ARV-related toxicities and co-morbidities, such as HAND.
• * The model offers an accessible platform for advancing HIV research and therapeutic development.