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.
Source: ScienceNOW - Category: Science Authors: Tags: Biochemistry, Microbiology reports Source Type: news

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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%)
Source: COPD: Journal of Chronic Obstructive Pulmonary Disease - Category: Respiratory Medicine Tags: COPD Source Type: research
Dr Paul Sax gives answers to some of the most commonly asked questions he has received from patients with HIV.Medscape HIV/AIDS
Source: Medscape Hiv-Aids Headlines - Category: Infectious Diseases Tags: HIV/AIDS Commentary Source Type: news
Authors: Whiteside A, Parker W, Schramm M PMID: 32233915 [PubMed - as supplied by publisher]
Source: African Journal of AIDS Research - Category: African Health Tags: Afr J AIDS Res Source Type: research
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]
Source: International Journal of Qualitative Studies on Health and Well-being - Category: International Medicine & Public Health Tags: Int J Qual Stud Health Well-being Source Type: research
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...
Source: Assistive Technology - Category: Rehabilitation Tags: Assist Technol Source Type: research
Authors: Wilkinson L, Siberry GK, Golin R, Phelps BR, Wolf HT, Modi S, Grimsrud A PMID: 32239657 [PubMed - as supplied by publisher]
Source: Journal of the International AIDS Society - Category: Infectious Diseases Tags: J Int AIDS Soc Source Type: research
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...
Source: AIDS and Behavior - Category: Infectious Diseases Source Type: research
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 ...
Source: AIDS and Behavior - Category: Infectious Diseases Source Type: research
' 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
Source: Medscape Hiv-Aids Headlines - Category: Infectious Diseases Tags: Internal Medicine Expert Interview Source Type: news
BEST supplements for hair growth: The quest for a magical pill to help aid in hair growth is not always feasible. However, sometimes one can turn to the power of the plants and this particular medical herb is known to improve circulation which aids in hair growth.
Source: Daily Express - Health - Category: Consumer Health News Source Type: news
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