Humanized mice recapitulate key features of HIV-1 infection: a novel concept using long-acting anti-retroviral drugs for treating HIV-1

人源化小鼠重现 HIV-1 感染的主要特征:使用长效抗逆转录病毒药物治疗 HIV-1 的新概念

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作者:Marc Nischang, Roger Sutmuller, Gustavo Gers-Huber, Annette Audigé, Duo Li, Mary-Aude Rochat, Stefan Baenziger, Ursula Hofer, Erika Schlaepfer, Stephan Regenass, Katie Amssoms, Bart Stoops, Anja Van Cauwenberge, Daniel Boden, Guenter Kraus, Roberto F Speck

Background

Humanized mice generate a lymphoid system of human origin subsequent to transplantation of human CD34+ cells and thus are highly susceptible to HIV infection. Here we examined the efficacy of antiretroviral treatment (ART) when added to food pellets, and of long-acting (LA) antiretroviral compounds, either as monotherapy or in combination. These studies shall be inspiring for establishing a gold standard of ART, which is easy to administer and well supported by the mice, and for subsequent studies such as latency. Furthermore, they should disclose whether viral breakthrough and emergence of resistance occurs similar as in HIV-infected patients when ART is insufficient.

Significance

This report is a unique description of multiple aspects of HIV infection in humanized mice that comprised efficacy testing of various treatment regimens, including LA compounds, resistance mutation analysis as well as viral rebound after treatment interruption. Humanized mice will be highly valuable for exploring the antiviral potency of new compounds or compounds targeting the latent HIV reservoir.

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