commercial participation in, or funding of, guideline projects. Drafts of the guideline have been reviewed by at least three AAN committees, a network of neurologists, Neurology peer reviewers and representatives from related fields. The AAN Guideline Author Conflict of Interest Policy can be Phloretin viewed at www.aan.com.Here we demonstrate that a combination of tenofovir, emtricitabine, and raltegravir effectively suppresses peripheral and systemic HIV replication in humanized BLT mice. We also demonstrate that antiretroviral therapy treated humanized BLT mice harbor latently infected resting human CD4 T cells that can be induced ex vivo to produce HIV. We observed that the levels of infected resting human CD4 T cells present in BLT mice are within the range of those observed circulating in patients undergoing suppressive ART.
These results demonstrate the potential of humanized BLT mice as an attractive model for testing the in vivo efficacy of novel HIV eradication strategies.Antiretroviral therapy is critical for improved quality of life HIF Signaling Pathway and long term survival in most human immunodeficiency virus infected patients. Unfortunately, ART is a lifelong commitment, because it is unable to eradicate HIV reservoirs and ART interruption is accompanied by viremia rebound . Thus, replication competent HIV persists in infected individuals despite ART induced reduction in plasma viral RNA. This persistent HIV infection in patients is thought to be predominantly due to the presence of latently infected resting CD4 T cells that survive despite long term ART .
Most analyses of latent but replication competent HIV 1 in humans have been limited to the recovery of virus from resting CD4 T cells in peripheral blood . A few studies have analyzed paraffin virus recovered from lymph node samples . However, it is clear that other anatomical sites are involved in the persistence of HIV during ART . Successful eradication of the HIV that persists during ART hinges on an improved understanding of the nature of the latent viral reservoir, and validated animal models that recapitulate key aspects of the human condition are critical to this effort . Peripheral blood and lymphoid and nonlymphoid tissues of nonhuman primates receiving ART have been evaluated for the presence of latently infected resting CD4 T cells .
These important studies involving simian immunodeficiency virus have provided significant insight into the location of productively infected cells in ART treated animals. Here we describe the implementation of a novel in vivo system to study HIV infection of resting human T cells, the humanized bone marrow/liver/thymus mouse model. Specifically, we first demonstrated the ability of anti HIV drugs to efficiently suppress HIV replication and then determined the presence of HIV infected resting CD4 T cells in BLT mice. Our results demonstrate that BLT mice represent an outstanding in vivo model of HIV latency that can be utilized to evaluate HIV eradication interventions. Humanized BLT mice are individually bioengineered by bone marrow transplant of CD34 hematopoietic progenitor cells into immunodeficient mice previously implanted with autologous liver and thymus tissue . Human hematopoietic cells are present in all tissues of BLT mice, luding peripheral blood.