Transmitted Drug Resistance in the CFAR Network of Integrated Clinical Systems Cohort: Prevalence and Effects on Pre-Therapy CD4 and Viral Load

Human immunodeficiency virus type 1 (HIV-1) genomes often carry one or more mutations associated with drug resistance upon transmission into a therapy-naïve individual. We assessed the prevalence and clinical significance of transmitted drug resistance (TDR) in chronically-infected therapy-naïve patients enrolled in a multi-center cohort in North America. Pre-therapy clinical significance was quantified by plasma viral load (pVL) and CD4+ cell count (CD4) at baseline. Naïve bulk sequences of HIV-1 protease and reverse transcriptase (RT) were screened for resistance mutations as defined by the World Health Organization surveillance list. The overall prevalence of TDR was 14.2%. We used a Bayesian network to identify co-transmission of TDR mutations in clusters associated with specific drugs or drug classes. Aggregate effects of mutations by drug class were estimated by fitting linear models of pVL and CD4 on weighted sums over TDR mutations according to the Stanford HIV Database algorithm. Transmitted resistance to both classes of reverse transcriptase inhibitors was significantly associated with lower CD4, but had opposing effects on pVL. In contrast, position-specific analyses of TDR mutations revealed substantial effects on CD4 and pVL at several residue positions that were being masked in the aggregate analyses, and significant interaction effects as well. Residue positions in RT with predominant effects on CD4 or pVL (D67 and M184) were re-evaluated in causal models using an inverse probability-weighting scheme to address the problem of confounding by other mutations and demographic or risk factors. We found that causal effect estimates of mutations M184V/I ( pVL) and D67N/G ( and pVL) were compensated by K103N/S and K219Q/E/N/R. As TDR becomes an increasing dilemma in this modern era of highly-active antiretroviral therapy, these results have immediate significance for the clinical management of HIV-1 infections and our understanding of the ongoing adaptation of HIV-1 to human populations

High Levels of Antiretroviral Use and Viral Suppression Among Persons in HIV Care in the United States, 2010

Contemporary data on patterns of antiretroviral therapy (ART) use in the U.S. are needed to inform efforts to improve the HIV care cascade

Design and Implementation of a Facility for Discovering New Scintillator Materials

We describe the design and operation of a high-throughput facility for synthesizing thousands of inorganic crystalline samples per year and evaluating them as potential scintillation detector materials. This facility includes a robotic dispenser, arrays of automated furnaces, a dual-beam X-ray generator for diffractometery and luminescence spectroscopy, a pulsed X-ray generator for time response measurements, computer-controlled sample changers, an optical spectrometer, and a network-accessible database management system that captures all synthesis and measurement data

Comparative effectiveness of single versus multiple tablet antiretroviral therapy regimens in clinical HIV practice

Abstract We determined risk of virologic failure (VF) in individuals initiating tenofovir/emtricitabine/efavirenz as single versus multiple tablet regimens (MTR). We found no significant difference in the risk of VF, though did observe a trend toward more VF and M184 V mutations among persons initiating MTR. Temporal trends in care may have confounded results

A Comparison of Neuroelectrophysiology Databases

As data sharing has become more prevalent, three pillars - archives, standards, and analysis tools - have emerged as critical components in facilitating effective data sharing and collaboration. This paper compares four freely available intracranial neuroelectrophysiology data repositories: Data Archive for the BRAIN Initiative (DABI), Distributed Archives for Neurophysiology Data Integration (DANDI), OpenNeuro, and Brain-CODE. These archives provide researchers with tools to store, share, and reanalyze neurophysiology data though the means of accomplishing these objectives differ. The Brain Imaging Data Structure (BIDS) and Neurodata Without Borders (NWB) are utilized by these archives to make data more accessible to researchers by implementing a common standard. While many tools are available to reanalyze data on and off the archives' platforms, this article features Reproducible Analysis and Visualization of Intracranial EEG (RAVE) toolkit, developed specifically for the analysis of intracranial signal data and integrated with the discussed standards and archives. Neuroelectrophysiology data archives improve how researchers can aggregate, analyze, distribute, and parse these data, which can lead to more significant findings in neuroscience research.Comment: 25 pages, 8 figures, 1 tabl