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https://www.readbyqxmd.com/read/30322148/development-of-novel-intramolecular-fret-based-abc-transporter-biosensors-to-identify-new-substrates-and-modulators
#1
Bremansu Osa-Andrews, Kee W Tan, Angelina Sampson, Surtaj H Iram
Multidrug resistance protein 1 (MRP1) can efflux a wide variety of molecules including toxic chemicals, drugs, and their derivatives out of cells. Substrates of MRP1 include anti-cancer agents, antibiotics, anti-virals, anti-human immunodeficiency virus (HIV), and many other drugs. To identify novel substrates and modulators of MRP1 by exploiting intramolecular fluorescence resonance energy transfer (FRET), we genetically engineered six different two-color MRP1 proteins by changing green fluorescent protein (GFP) insertion sites, while keeping the red fluorescent protein (RFP) at the C-terminal of MRP1...
October 13, 2018: Pharmaceutics
https://www.readbyqxmd.com/read/30318900/perceived-hiv-risk-as-a-predictor-of-sexual-risk-behaviors-and-discrimination-among-high-risk-women
#2
Whitney C Sewell, Stephanie A Blankenship
HIV risk perception and discrimination are important determinants of HIV prevention among vulnerable populations. Using Detroit's 2016 National HIV Behavioral Surveillance (NHBS) Survey, we evaluated demographic variables, risk behaviors, and perception of HIV stigma and discrimination stratified by perceived HIV risk (high, medium, low) in a sample of high-risk women. Significant variables were identified using Pearson Chi-squared tests and one-way analysis of variance tests. Among 541 females surveyed, 93...
October 14, 2018: AIDS Care
https://www.readbyqxmd.com/read/30310965/enhancement-in-the-catalytic-activity-of-sulfolobus-solfataricus-p2-%C3%AE-lactamase-by-semi-rational-design-with-the-aid-of-a-newly-established-high-throughput-screening-method
#3
Shuaihua Gao, Yingxiu Lu, Yuanyuan Li, Rong Huang, Guojun Zheng
(-)-γ-Lactam ((-)-2-azabicyclo[2.2.1]hept-5-en-3-one) has attracted increasing attention as the chiral intermediate of carbocyclic nucleosides most of which serve as pharmaceutical agents such as anti-HIV/HBV drugs abacavir and carbovir. So far, developing in vitro (+)-γ-lactamase-mediated biotransformation has been one of the most efficient approaches for the production of (-)-γ-lactam. In this study, the catalytic activity of the (+)-γ-lactamase from Sulfolobus solfataricus P2 was engineered by semi-rational design...
October 11, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/30309292/the-art-of-antiretroviral-therapy-in-critically-ill-patients-with-hiv
#4
Tyler Finocchio, William Coolidge, Thomas Johnson
The management of patients with human immunodeficiency virus (HIV) can be a complicated specialty within itself, made even more complex when there are so many unanswered questions regarding the care of critically ill patients with HIV. The lack of consensus on the use of antiretroviral medications in the critically ill patient population has contributed to an ongoing clinical debate among intensivists. This review focuses on the pharmacological complications of antiretroviral therapy (ART) in the intensive care setting, specifically the initiation of ART in patients newly diagnosed with HIV, immune reconstitution inflammatory syndrome (IRIS), continuation of ART in those who were on a complete regimen prior to intensive care unit admission, barriers of drug delivery alternatives, and drug-drug interactions...
October 11, 2018: Journal of Intensive Care Medicine
https://www.readbyqxmd.com/read/30306437/client-and-provider-perspectives-on-antiretroviral-treatment-uptake-and-adherence-among-people-who-inject-drugs-in-indonesia-ukraine-and-vietnam-hptn-074
#5
Vivian F Go, Rebecca B Hershow, Tetiana Kiriazova, Riza Sarasvita, Quynh Bui, Carl A Latkin, Scott Rose, Erica Hamilton, Kathryn E Lancaster, David Metzger, Irving F Hoffman, William C Miller
HIV-infected people who inject drugs (PWID) have low uptake of HIV services, increasing the risk of transmission to uninfected injection or sexual partners and the likelihood of AIDS-related deaths. HPTN 074 is a vanguard study assessing the feasibility of an integrated intervention to facilitate treatment as prevention to PWID in Indonesia, Ukraine, and Vietnam. We describe barriers to and facilitators of ART uptake and adherence among PWID. We conducted in-depth interviews with 62 participants, including 25 providers and 37 PWID at baseline across all sites...
October 10, 2018: AIDS and Behavior
https://www.readbyqxmd.com/read/30306175/sulfono-%C3%AE-aa-modified-peptides-that-inhibit-hiv-1-fusion
#6
Olapeju Bolarinwa, Meng Zhang, Erin Mulry, Min Lu, Jianfeng Cai
The utilization of bioactive peptides in the development of highly selective and potent pharmacological agents for the disruption of protein-protein interactions is appealing for drug discovery. It is known that HIV-1 entry into a host cell is through a fusion process that is mediated by the trimeric viral glycoprotein gp120/41, which is derived from gp160 through proteolytic processing. Peptides derived from the HIV gp41 C-terminus have proven to be potent in inhibiting the fusion process. These peptides bind tightly to the hydrophobic pocket on the gp-41 N-terminus, which was previously identified as a potential inhibitor binding site...
October 11, 2018: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/30302572/pharmacokinetic-considerations-with-the-use-of-antiepileptic-drugs-in-patients-with-hiv-and-organ-transplants
#7
REVIEW
Jorge J Asconapé
PURPOSE OF REVIEW: Antiepileptic drugs are frequently administered to patients with HIV infection or in recipients of organ transplants. The potentially serious drug-drug interactions between the "classic" antiepileptic drugs, antiretrovirals, and immunosuppressants have been extensively studied. Evidence-based information on the second and third generation of antiepileptic drugs is almost non-existent. The purpose of this review is to analyze the pharmacokinetic profile of these newer agents to assess their potential for drug interactions with antiretrovirals and immunosuppressants...
October 9, 2018: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/30296952/experiencing-syndemic-disentangling-the-biosocial-complexity-of-tuberculosis-through-qualitative-research
#8
Olga Zvonareva, Willemien van Bergen, Nadezhda Kabanets, Aleksander Alliluyev, Olga Filinyuk
Tuberculosis (TB) remains a major global public health problem that has become a crisis fuelled by HIV and the increasing occurrence of antimicrobial resistance. What has been termed the biosocial nature of TB challenges effective control of the disease. Yet, biosocial interactions involved in the persistence of TB in diverse settings are difficult to systematically account for. The recently developed framework of syndemics provides a way to capture how complex health problems result from the interactions between diseases such as HIV and TB, and harmful social conditions such as unemployment, malnutrition and substance abuse...
October 9, 2018: Journal of Biosocial Science
https://www.readbyqxmd.com/read/30296620/design-and-development-of-ph-responsive-polyurethane-membranes-for-intravaginal-release-of-nanomedicines
#9
Seungil Kim, Yannick Leandre Traore, Emmanuel A Ho, Muhammad Shafiq, Soo-Hyun Kim, Song Liu
The objective of this study was to develop and characterize a novel intravaginal membrane platform for pH-triggered release of nanoparticles (NPs), which is essential for efficient intravaginal delivery of certain effective but acid-labile therapeutic agents for sexually transmitted infections, such as small interfering RNA (siRNA). pH-responsive polyurethane (PU) was electrospun into a porous nanofibrous membrane. The diameters of the fibers, as well as the thickness and pore sizes of the membrane under dry and wet conditions (pH 4...
October 5, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/30295215/drug-drug-interactions-and-clinical-considerations-with-co-administration-of-antiretrovirals-and-psychotropic-drugs
#10
Kellie J Goodlet, Monika T Zmarlicka, Alyssa M Peckham
Psychotropic medications are frequently co-prescribed with antiretroviral therapy (ART), owing to a high prevalence of psychiatric illness within the population living with HIV, as well as a 7-fold increased risk of HIV infection among patients with psychiatric illness. While ART has been notoriously associated with a multitude of pharmacokinetic drug interactions involving the cytochrome P450 enzyme system, the magnitude and clinical impact of these interactions with psychotropics may range from negligible effects on plasma concentrations to life-threatening torsades de pointes or respiratory depression...
October 8, 2018: CNS Spectrums
https://www.readbyqxmd.com/read/30295184/phenylboronic-acid-polymers-for-biomedical-applications
#11
Ji Hyun Ryu, Gyeong Jin Lee, Yu-Ru V Shih, Tae-Il Kim, Shyni Varghese
BACKGROUND: Phenylboronic acid-polymers (PBA-polymers) have attracted tremendous attention as potential stimuli-responsive materials with applications in drug-delivery depots, scaffolds for tissue engineering, HIV barriers, and biomolecule-detecting/sensing platforms. The unique aspect for PBA-polymers is their interactions with diols, which results in reversible, covalent bond formations. This very nature of reversible bonding between boronic acids and diols has been fundamental to their applications in the biomedical area...
October 8, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/30292749/a-novel-multivalent-dna-helix-based-inhibitor-showed-enhanced-anti-hiv-1-fusion-activity
#12
Yongjia Tang, Zeye Han, Hongqian Ren, Jiamei Guo, Huihui Chong, Yangli Tian, Keliang Liu, Liang Xu
DNA helix-based HIV-1 fusion inhibitors have been discovered as potent drug candidates, but further research is required to enhance their efficiency. The trimeric structure of the HIV-1 envelope glycoprotein provides a structural basis for multivalent drug design. In this work, a "multi-domain" strategy was adopted for design of an oligodeoxynucleotide with assembly, linkage, and activity domains. Built on the self-assembly of higher-order nucleic acid structure, a novel category of multivalent DNA helix-based HIV-1 fusion inhibitor could be easily obtained by a simple annealing course in solution buffer, with no other chemical synthesis for multivalent connection...
October 4, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/30289816/variation-in-antiretroviral-treatment-art-coverage-and-virological-suppression-among-three-hiv-key-populations
#13
Kamilla Grønborg Laut, Leah Shepherd, Magnus Gottfredsson, Dalibor Sedlacek, Brygida Knysz, Josip Begovac, Roxana Radoi, Brigitte Schmied, Nikoloz Chkhartishvili, Eric Florence, Matti Ristola, Gerd Fätkenheuer, Fiona Mulcahy, Patrick Schmid, Elena Kuzovatova, Dzmitry Paduta, Jelena Smidt, Pere Domingo, Janos Szlávik, Jens Lundgren, Amanda Mocroft, Ole Kirk
OBJECTIVES: We assessed differences in antiretroviral treatment (ART) coverage and virological suppression across three HIV key populations, as defined by self-reported HIV transmission category: sex between men, injection drug use [IDU] and heterosexual transmission. DESIGN: Multinational cohort study. METHODS: Within the EuroSIDA study, we assessed region-specific percentages of ART-coverage among those in care and virological suppression (<500 copies/mL) among those on ART,, and analyzed differences between transmission categories using logistic regression...
October 4, 2018: AIDS
https://www.readbyqxmd.com/read/30288468/drug-resistance-mutation-l76v-alters-nonpolar-interactions-at-the-flap-core-interface-of-hiv-1-protease
#14
Andres Wong-Sam, Yuan-Fang Wang, Ying Zhang, Arun K Ghosh, Robert W Harrison, Irene T Weber
Four HIV-1 protease (PR) inhibitors, clinical inhibitors lopinavir and tipranavir, and two investigational compounds 4 and 5 , were studied for their effect on the structure and activity of PR with drug-resistant mutation L76V (PRL76V ). Compound 5 exhibited the best K i value of 1.9 nM for PRL76V , whereas the other three inhibitors had K i values of 4.5-7.6 nM, 2-3 orders of magnitude worse than for wild-type enzymes. Crystal structures showed only minor differences in interactions of inhibitors with PRL76V compared to wild-type complexes...
September 30, 2018: ACS Omega
https://www.readbyqxmd.com/read/30286041/preventive-therapy-for-hiv-associated-tuberculosis
#15
Betina Durovni, Solange Cavalcante
PURPOSE OF REVIEW: Tuberculosis (TB) remains the leading cause of death in people living with HIV (PLHIV) despite the achievements in antiretroviral therapy coverage. TB preventive therapy (TPT) has proved efficacy but has been neglected and poorly implemented. We reviewed recent publications and guidelines about TPT in PLHIV. RECENT FINDINGS: High-quality studies showed that TPT has a durable effect, over 5 years, preventing TB and all-cause mortality. There is new evidence showing the noninferiority of shorter, rifamycin-based regimens of TPT increasing the options for treatment...
November 2018: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/30286040/hiv-associated-pediatric-tuberculosis-prevention-diagnosis-and-treatment
#16
Alexander Kay, Anthony J Garcia-Prats, Anna Maria Mandalakas
PURPOSE OF REVIEW: The detrimental synergy of colliding HIV and tuberculosis (TB) epidemics is most devastating among children and adolescents living with HIV (CALWH) who shoulder a disproportionate burden of all child TB mortality. RECENT FINDINGS: CALWH benefit less from Bacille-Calmette Guerin vaccination than HIV-uninfected children and are not receiving TB preventive therapy despite global recommendations. Further, the predictive utility of most diagnostic tools is reduced in CALWH...
November 2018: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/30273891/differential-relationships-between-cannabis-consumption-and-sleep-health-as-a-function-of-hiv-status
#17
Aaron C Lim, April D Thames
BACKGROUND: There is evidence that regular cannabis use has negative effects on sleep health. Relative to HIV- populations, HIV + individuals consistently report greater sleep impairments. The number of HIV + individuals reporting frequent cannabis use, often to treat sleep issues, has significantly increased recently. It is unknown, however, if HIV status moderates the association between cannabis use and sleep health. The current study, therefore, examines these associations in a sample of HIV + and HIV- adults...
September 5, 2018: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/30264826/-tolerability-of-current-antiretroviral-single-tablet-regimens
#18
Pere Domingo, Mª Gracia Mateo, Mª Del Mar Gutierrez, Francesc Vidal
The advent of protease inhibitors (PI) in the mid-nineties and its use as part of triple combinations revolutionized the management of HIV infection. Since then, progression to AIDS and AIDS-related deaths can be prevented. However, antiretroviral therapy based on PI has been discouraged for a while given its lower tolerability compared to alternative options; and only recent improvements in pharmacotherapy have renewed the interest for the newest agents within this class. First, the tolerability of the latest PI darunavir (DRV) and atazanavir is much better than for older PI, such as indinavir or lopinavir...
2018: AIDS Reviews
https://www.readbyqxmd.com/read/30260044/exploring-molecular-mechanism-of-allosteric-inhibitor-to-relieve-drug-resistance-of-multiple-mutations-in-hiv-1-protease-by-enhanced-conformational-sampling
#19
Jianzhong Chen, Cheng Peng, Jinan Wang, Weiliang Zhu
Recently, allosteric regulations of HIV-1 protease (PR) is suggested as a promising approach to relieve drug resistance of mutations toward inhibitors targeting the active site of PR. Replica-exchange molecular dynamics (REMD) simulations and normal mode analysis (NMA) are integrated to enhance conformational sampling of PR. Molecular mechanics generalized Born surface area (MM-GBSA) method was applied to calculate binding free energies of three inhibitors APV, DRV and NIT to the wild-type (WT) and multidrug resistance (MDR) PRs...
September 27, 2018: Proteins
https://www.readbyqxmd.com/read/30251609/rational-design-of-colchicine-derivatives-as-anti-hiv-agents-via-qsar-and-molecular-docking
#20
Apilak Worachartcheewan, Napat Songtawee, Suphakit Siriwong, Supaluk Prachayasittikul, Chanin Nantasenamat, Virapong Prachayasittikul
BACKGROUND: Human immunodeficiency virus (HIV) is an infective microorganism that causes an acquired immunodeficiency syndrome (AIDS). Therefore, the rational design of inhibitors for preventing the progression of the disease is required. OBJECTIVE: This study aims to construct quantitative structure-activity relationship (QSAR) models, molecular docking and newly design of colchicine and derivatives with anti-HIV activity. METHOD: A data set of 24 colchicine and derivatives with anti-HIV activity were employed to develop QSAR models using machine learning methods (e...
September 24, 2018: Medicinal Chemistry
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