HIV hu-mouse models

HIV is a human specific virus targeting human CD4+ circulating lymphocytes. During the past 10 years, the development of the reconstitution of a full functional human immune system in immune deficient mouse models has provided the opportunity to setup HIV hu-mouse models. Compared to SIV monkey models, HIV mice are cheaper, safer, and ethically acceptable. Current tri-therapy are showing similar efficacy on HIV mice than on HIV patients and combotherapy designs can be executed nicely with HIV hu-mice.

HIV hu-mice

Hu-mice can be infected with various strain of HIV and few weeks later, in vivo profiling of new anti-HIV drug candidates can be initiated. Typically, we assess efficacy, resistance, rebound, latency and combotherapy strategies, as HIV infection leads to a stable and elevated viral load in the blood. Conventional HAART therapy for 3 weeks decreases by 95% the circulating HIV viral load, and treatment cessation induces a rebound as observed in HIV/AIDS patients. Different HIV strains can be used for the successful infection of hu-mice. Cytolytic and cytopathic effects have been studied on human CD4 positive lymphocytes from HIV mice.

HIV infection

HIV Mouse Infection as in Human

Typical data illustrating :

Efficacy of HAART
Rebound after treatment cessation

Selection For Best Clinical Candidates

Hu-mouse infected with Yu2 HIV Strain
Anti-Viral treatment initiated 5 weeks after infection

Cytolytic and Cytostatic HIV Strains

Hu-mouse infected with cytolytic NL4-3 and cytostatic Yu2 HIV Strain
Percentage of CD4+ cells among CD3+ cells determined by Flow Cytometry analysis

Strengh of HIV Mouse Models

We are convinced that using HIV hu-mouse models is the most efficiency process for getting preclinical candidate efficacy translational data for further clinical testing:

Full blown HIV infection (106-107 HIV load/ml) within 4-5 weeks
95% decrease of HIV load upon HAART treatment in <14 days
IP, IV or vaginal routes of infection
R5 and X4 tropism reconstitution
Cytolytic activity of X4-HIV strain as in human
Combotherapy strategy for selection of best clinical candidates/schedule/regimen
Latency and rebound protocols for disease management with mAbs & small NCE’s