The impact of COVID-19 on the HIV continuum of care: challenges, innovations, and opportunities.

INTRODUCTION: In February 2019, the United States (US) launched the Ending the HIV Epidemic (EHE) initiative with emphasis on improving the various steps of the Human Immunodeficiency Virus (HIV) prevention and care continuum. However, in March 2020, the Coronavirus Disease 2019 (COVID-19) pandemic was declared, curtailing efforts to end the epidemic in the US. AREAS COVERED: To describe the impact of the pandemic on EHE in the US, the authors performed a comprehensive literature review focusing on outcomes at each step of the HIV care continuum. Simultaneously, they identified examples of pandemic-era innovations that may help EHE. EXPERT OPINION: Numerous studies demonstrated pandemic-related disruptions across the care continuum as well as the impact on preexisting barriers to care among People with HIV (PWH) at higher risk for poor outcomes. As the pandemic progressed, innovative approaches to delivering healthcare and providing essential services emerged, including widespread use of telemedicine, expansion of home-based care, self-collected sexually transmitted infection (STI) and HIV testing, and co-located testing for COVID-19 and HIV/STIs. While the COVID-19 pandemic initially hindered achieving EHE in the US, the ability to be agile, flexible, and creative led to innovation in HIV care delivery that may ultimately assist in meeting EHE goals as we transition into the post-pandemic era.

Mutations in SIX1 Associated with Branchio-oto-Renal Syndrome (BOR) Differentially Affect Otic Expression of Putative Target Genes.

Several single-nucleotide mutations in SIX1 underlie branchio-otic/branchio-oto-renal (BOR) syndrome, but the clinical literature has not been able to correlate different variants with specific phenotypes. We previously assessed whether variants in either the cofactor binding domain (V17E, R110W) or the DNA binding domain (W122R, Y129C) might differentially affect early embryonic gene expression, and found that each variant had a different combination of effects on neural crest and placode gene expression. Since the otic vesicle gives rise to the inner ear, which is consistently affected in BOR, herein we focused on whether the variants differentially affected the otic expression of genes previously found to be likely Six1 targets. We found that V17E, which does not bind Eya cofactors, was as effective as wild-type Six1 in reducing most otic target genes, whereas R110W, W122R and Y129C, which bind Eya, were significantly less effective. Notably, V17E reduced the otic expression of prdm1, whereas R110W, W122R and Y129C expanded it. Since each mutant has defective transcriptional activity but differs in their ability to interact with Eya cofactors, we propose that altered cofactor interactions at the mutated sites differentially interfere with their ability to drive otic gene expression, and these differences may contribute to patient phenotype variability.