David T Evans1, Guido Silvestri. 1. New England National Primate Research Center, Harvard Medical School, Southborough, Massachusetts, USA.
Abstract
PURPOSE OF REVIEW: Over the past decades, AIDS research has made tremendous progress in all key areas, including pathogenesis, prevention, and treatment. In particular, the introduction of potent antiretroviral therapy (ART) has dramatically reduced the morbidity and mortality of HIV-infected individuals. However, several challenges remain, including the absence of a vaccine that can reliably prevent virus acquisition, and the inability of current ART regimens to eradicate the infection. RECENT FINDINGS: Several key advances in HIV/AIDS research have been made possible by the extensive use of animal models and, in particular, the nonhuman primate models of SIV and SHIV infection of various monkey species including macaques, sooty mangabeys, vervets, and others. Key advantages of these models include the ability to control for parameters that are virtually impossible to assess in humans, to extensively study cells and tissues (including elective necropsy), and to perform proof-of-concept studies that would pose unacceptable safety risks in humans. SUMMARY: In this review, we describe the most recent advances in the use of animal models for HIV/AIDS research, and will break down these advances in three areas: models for virus transmission, dissemination, and pathogenesis; models for virus prevention and vaccines; and models for virus eradication and indefinite virus containment (functional cure) under ART.
PURPOSE OF REVIEW: Over the past decades, AIDS research has made tremendous progress in all key areas, including pathogenesis, prevention, and treatment. In particular, the introduction of potent antiretroviral therapy (ART) has dramatically reduced the morbidity and mortality of HIV-infected individuals. However, several challenges remain, including the absence of a vaccine that can reliably prevent virus acquisition, and the inability of current ART regimens to eradicate the infection. RECENT FINDINGS: Several key advances in HIV/AIDS research have been made possible by the extensive use of animal models and, in particular, the nonhuman primate models of SIV and SHIV infection of various monkey species including macaques, sooty mangabeys, vervets, and others. Key advantages of these models include the ability to control for parameters that are virtually impossible to assess in humans, to extensively study cells and tissues (including elective necropsy), and to perform proof-of-concept studies that would pose unacceptable safety risks in humans. SUMMARY: In this review, we describe the most recent advances in the use of animal models for HIV/AIDS research, and will break down these advances in three areas: models for virus transmission, dissemination, and pathogenesis; models for virus prevention and vaccines; and models for virus eradication and indefinite virus containment (functional cure) under ART.
Authors: J R Mascola; G Stiegler; T C VanCott; H Katinger; C B Carpenter; C E Hanson; H Beary; D Hayes; S S Frankel; D L Birx; M G Lewis Journal: Nat Med Date: 2000-02 Impact factor: 53.440
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