4.4 Article

A humanized mouse model for HIV-2 infection and efficacy testing of a single-pill triple-drug combination anti-retroviral therapy

期刊

VIROLOGY
卷 501, 期 -, 页码 115-118

出版社

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2016.11.013

关键词

Animal model for HIV-2 infection and therapy; HIV-2 therapeutic testing in humanized mice; Single-pill triple-drug therapy fot HIV-2; Triple-drug Triumeq therapy for HIV; Combinatorial ART for HIV; Humanized mice for HIV research

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资金

  1. NIH, USA [RO1 AI100845, RO1 AI120021]

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While HIV-2 is a causative agent for AIDS in addition to the better studied HIV-1, there is currently no suitable animal model for experimental studies for HIV-2 infection and evaluating promising drugs in vivo. Here we evaluated humanized mice for their susceptibility to HIV-2 infection and tested a single-pill three drug formulation of anti-retrovirals (NRTIs abacavir and lamivudine, integrase inhibitor dolutegravir) (trade name, Triumeq(R)). Our results showed that hu-mice are susceptible to HIV-2 infection showing persistent viremia and CD4 T cell loss, key hallmarks of AIDS pathogenesis. Oral drug treatment led to full viral suppression and protection from CD4 T cell depletion. Cessation of therapy resulted in viral rebound and CD4 T cell loss. These proof-of-concept studies establish the utility of hu-mice for evaluating HIV-2 pathogenesis in more detail in the future, testing novel therapies and providing pre-clinical efficacy data of a three drug combination to treat HIV-2 infections.

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