Accelerating Human Immunodeficiency Virus Self-Testing in the United States: A Call to Action.

Human immunodeficiency virus (HIV) self-testing has emerged as a tool to increase the proportion of people to know their status. Since the first HIV self-test was approved in 2012 by the US Food and Drug Administration (FDA), global access to HIV self-tests has been bolstered by public-private partnerships to ensure equitable access in low- and middle-income countries. However, no company has applied for FDA clearance in a decade. We highlight the potential benefits to reclassifying HIV self-tests from class III to class II.

Highlighting and addressing barriers to widespread adaptation of HIV self-testing in the United States.

INTRODUCTION: HIV self-testing (HIVST), whereby an individual performs and interprets their own rapid screening test at home, is another tool to increase the proportion of at-risk individuals who know their status. Globally, HIVST has rapidly been adopted through global partnerships to ensure equitable access to tests in low- and middle-income countries (LMIC). AREA COVERED: This review discusses the regulatory burdens of HIV self-testing within the United States while examining the use of HIV self-tests on a global scale. While the United States only has one approved HIV self-test, numerous tests have been prequalified by the WHO. EXPERT OPINION: Despite the US Food and Drug Administration (FDA) clearance of the first and only self-test in 2012, there have been no other tests that have undergone FDA consideration due to regulatory barriers. This, in turn, has stifled market competition. Despite existing evidence that such programs are an innovative approach to testing hesitant or hard-to-reach populations, high individual test cost and bulky packaging make large-scale, mail-out, and HIV self-testing programs expensive. COVID-19 pandemic has accelerated the public demand for self-testing - HIV self-test programs should capitalize on this to increase the proportion of at-risk people who know their status and are linked to care to contribute to ending the HIV epidemic.

Gene silencing by EZH2 suppresses TGF-ß activity within the decidua to avert pregnancy-adverse wound healing at the maternal-fetal interface.

A little-appreciated feature of early pregnancy is that embryo implantation and placental outgrowth do not evoke wound-healing responses in the decidua, the specialized endometrial tissue that surrounds the conceptus. Here, we provide evidence that this phenomenon is partly due to an active program of gene silencing mediated by EZH2, a histone methyltransferase that generates repressive histone 3 lysine 27 trimethyl (H3K27me3) histone marks. We find that pregnancies in mice with EZH2-deficient decidual stromal cells frequently fail by mid-gestation, with the decidua showing ectopic myofibroblast formation, peri-embryonic collagen deposition, and gene expression profiles associated with transforming growth factor ß (TGF-ß)-driven fibroblast activation and fibrogenic extracellular matrix (ECM) remodeling. Analogous responses are observed when the mutant decidua is surgically wounded, while blockade of TGF-ß receptor signaling inhibits the defects and improves reproductive outcomes. Together, these results highlight a critical feature of reproductive success and have implications for the context-specific control of TGF-ß-mediated wound-healing responses elsewhere in the body.

Relief of tumor hypoxia unleashes the tumoricidal potential of neutrophils.

Polymorphonuclear neutrophils (PMNs) are increasingly recognized to influence solid tumor development, but why their effects are so context dependent and even frequently divergent remains poorly understood. Using an autochthonous mouse model of uterine cancer and the administration of respiratory hyperoxia as a means to improve tumor oxygenation, we provide in vivo evidence that hypoxia is a potent determinant of tumor-associated PMN phenotypes and direct PMN-tumor cell interactions. Upon relief of tumor hypoxia, PMNs were recruited less intensely to the tumor-bearing uterus, but the recruited cells much more effectively killed tumor cells, an activity our data moreover suggested was mediated via their production of NADPH oxidase-derived reactive oxygen species and MMP-9. Simultaneously, their ability to promote tumor cell proliferation, which appeared to be mediated via their production of neutrophil elastase, was rendered less effective. Relieving tumor hypoxia thus greatly improved net PMN-dependent tumor control, leading to a massive reduction in tumor burden. Remarkably, this outcome was T cell independent. Together, these findings identify key hypoxia-regulated molecular mechanisms through which PMNs directly induce tumor cell death and proliferation in vivo and suggest that the contrasting properties of PMNs in different tumor settings may in part reflect the effects of hypoxia on direct PMN-tumor cell interactions.