Structural basis of second-generation HIV integrase inhibitor action and viral resistance
Although second-generation HIV integrase strand-transfer inhibitors (INSTIs) are prescribed throughout the world, the mechanistic basis for the superiority of these drugs is poorly understood. We used single-particle cryo–electron microscopy to visualize the mode of action of the advanced INSTIs dolutegravir and bictegravir at near-atomic resolution. Glutamine-148->histidine (Q148H) and glycine-140->serine (G140S) amino acid substitutions in integrase that result in clinical INSTI failure perturb optimal magnesium ion coordination in the enzyme active site. The expanded chemical scaffolds of second-generation compounds mediate interactions with the protein backbone that are critical for antagonizing viruses containing the Q148H and G140S mutations. Our results reveal that binding to magnesium ions underpins a fundamental weakness of the INSTI pharmacophore that is exploited by the virus to engender resistance and provide a structural framework for the development of this class of anti-HIV/AIDS therapeutics.
The objective of this study was to test the value of adding a maximal inspiratory manoeuvre to basic spirometry to differentiate COPD and BA. One hundred forty-three COPD patients and 142 BA patients had measurements of maximal inspiratory and expiratory flow during routine spirometry. Parameters from these tests were used to assess diagnostic accuracy using receiver-operating characteristic (ROC) analyses followed by logistic regression. The association of two independent parameters were analyzed using linear regression analyses. Results show that forced expiratory volume in one second/forced vital capacity (FEV1/FVC%)
Dr Paul Sax gives answers to some of the most commonly asked questions he has received from patients with HIV.Medscape HIV/AIDS
Authors: Whiteside A, Parker W, Schramm M PMID: 32233915 [PubMed - as supplied by publisher]
Conclusions: Both intrinsic and extrinsic factors influence walking in adults with CP. Reflections by the adults with CP suggest these features may reduce participation in public spaces and potentially increase acceptance and use of mobility aids. PMID: 32238123 [PubMed - in process]
Authors: Abreu D, Codina B, Toledo J, Suárez A Abstract One of the challenges faced by blind persons to achieve optimal mobility is the detection and avoidance of obstacles located in their travel path. Besides the widely used white cane, alternative or complementary devices have been developed, such as electronic aids that provide feedback about the environment. However, the devices available have been unable to provide an optimal solution with widespread acceptance, motivating the present work. The eBAT (electronic Buzzer for Autonomous Travel) is designed to offer optimal protection and employs the user's...
Authors: Wilkinson L, Siberry GK, Golin R, Phelps BR, Wolf HT, Modi S, Grimsrud A PMID: 32239657 [PubMed - as supplied by publisher]
AbstractYouth living with HIV (YLWH; aged 16 –24) are at elevated risk of alcohol and drug use. Studies in older populations have identified patterns or profiles of multiple substance use differentially associated with mental health and anti-retroviral therapy (ART) adherence. No studies of YLWH have yet examined such patterns. A sample of 1 79 YLWH, reporting ART non-adherence and alcohol use, were recruited at five Adolescent Trials Network clinics in urban areas of the US between November 2014 and August 2017. Participants completed the Alcohol Smoking and Substance Involvement Screening Test (ASSIST) to assess su...
This study used descriptive analysis of quantitative d ata (N = 99) and thematic analysis of qualitative interviews (n = 36) to compare participants recruited from a hospital-based detoxification (detox) unit, largely diagnosed with HIV pre-2012 (n = 63) vs. those recruited from public, urban sexual health clinics (SHCs), mainly diagnosed in 2012 or later (n = 36). Detox participants were significantly more knowledgeable than SHC participants about HIV treatment, except regarding TasP. SHC participants’ desire for rapid linkage to care and ART initiation was in ...
' Usually in our clinical practice, you feel confident about a lot of the therapies that you're considering,'Angela Rogers, MD, said. But everything in the ICU is different with COVID-19.Medscape
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