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https://www.readbyqxmd.com/read/30097436/equilibrative-nucleoside-transporter-1-ent1-slc29a1-facilitates-transfer-of-the-antiretroviral-drug-abacavir-across-the-placenta
#1
Lukas Cerveny, Zuzana Ptackova, Martina Ceckova, Rona Karahoda, Sara Karbanova, Lucie Jiraskova, Susan L Greenwood, Jocelyn D Glazier, Frantisek Staud
Abacavir is a preferred antiretroviral drug for preventing mother-to-child HIV transmission; however, mechanisms of its placental transfer have not been satisfactorily described to date. Because abacavir is a nucleoside-derived drug, we hypothesized that the nucleoside transporters, ENTs (SLC29A) and/or Na+ dependent CNTs (SLC28A), may play a role in its passage across the placenta. To test this hypothesis, we performed uptake experiments using BeWo cell line, human fresh villous fragments and microvillous plasma membrane (MVM) vesicles...
August 10, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/30096076/structural-and-functional-characterization-of-hiv-1-cell-fusion-inhibitor-t20
#2
Xiujuan Zhang, Xiaohui Ding, Yuanmei Zhu, Huihui Chong, Sheng Cui, Jinsheng He, Xinquan Wang, Yuxian He
OBJECTIVE: The peptide drug T20 (enfuvirtide), derived from the C-terminal heptad repeat region of HIV-1 gp41, is the only membrane fusion inhibitor available for treatment of viral infection; however, its mechanism of action remains elusive and its structural basis is lacking. DESIGN: We focused on determining the crystal structure of T20 in complex with N39, a target mimic peptide derived from the N-terminal heptad repeat region of gp41. Based on the structural information, the mechanisms of action of T20 and its resistance were further characterized...
August 8, 2018: AIDS
https://www.readbyqxmd.com/read/30093343/accelerated-and-premature-aging-characterizing-regional-cortical-volume-loss-in-human-immunodeficiency-virus-infection-contributions-from-alcohol-substance-use-and-hepatitis-c-coinfection
#3
Adolf Pfefferbaum, Natalie M Zahr, Stephanie A Sassoon, Dongjin Kwon, Kilian M Pohl, Edith V Sullivan
BACKGROUND: Life expectancy of successfully treated human immunodeficiency virus (HIV)-infected individuals is approaching normal longevity. The growing HIV population ≥50 years of age is now at risk of developing HIV-associated neurocognitive disorder, acquiring coinfection with the hepatitis C virus (HCV), and engaging in hazardous drinking or drug consumption that can adversely affect trajectories of the healthy aging of brain structures. METHODS: This cross-sectional/longitudinal study quantified regional brain volumes from 1101 magnetic resonance imaging scans collected over 14 years in 549 participants (25 to 75 years of age): 68 HIV-infected individuals without alcohol dependence, 60 HIV-infected individuals with alcohol dependence, 222 alcohol-dependent individuals, and 199 control subjects...
July 4, 2018: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
https://www.readbyqxmd.com/read/30087055/-radiotherapy-for-hiv-infected-patients
#4
L Quéro, A Gobert, J-P Spano
Since the advent of highly active antiretroviral therapy, cancer incidence is still 2 to 3-fold higher in patients infected by human immunodeficiency virus (HIV) than in the general population, with an increased incidence of malignancies not associated with acquired immunodeficiency syndrome (AIDS). HIV-infected patients cancer treatment does not differ from that in the general population. However, the management of those patients have some particularities due to preexisting comorbid conditions, including metabolic, cardiovascular, renal or hepatic complications and the risk for potential drug - drug interactions in HIV-infected patients...
August 4, 2018: Cancer Radiothérapie: Journal de la Société Française de Radiothérapie Oncologique
https://www.readbyqxmd.com/read/30080683/challenges-of-tb-and-hiv-co-treatment-updates-and-insights
#5
Jeffrey A Tornheim, Kelly E Dooley
PURPOSE OF REVIEW: In the past few years, tuberculosis (TB) has overtaken HIV as the infectious disease with the highest global mortality. Successful management of this syndemic will require improved diagnostic tests, shorter preventive therapies, and more effective treatments, particularly in light of drug-resistant TB. RECENT FINDINGS: Results from several major studies have been published or presented recently, including the development of a more sensitive rapid, molecular assay for TB; several new symptom-based screening tools; use of a 1-month regimen for TB prevention; the results of early vs...
August 4, 2018: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/30073873/hiv-clinical-updates-new-single-tablet-regimens
#6
Jamielynn C Sebaaly, Denise Kelley
OBJECTIVE: To review the pharmacokinetics, safety, common drug-drug interactions (DDIs), and advantages and disadvantages of new single-tablet regimens (STRs) approved since September 2016 for HIV-1 infection. DATA SOURCES: A search using PubMed was conducted (2004 through May 2018) using the following keywords: single tablet regimen AND HIV. Additionally, a PubMed search was conducted for each individual STR using the generic names of the agents. For specific STRs, additional search terms were added to narrow results...
August 3, 2018: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/30073843/modeling-the-hiv-1-antiretroviral-therapeutic-drug-interaction
#7
Michael H Cynamon, Ernest N Damianopoulos
To model the ART (antiretroviral therapeutic) drug interaction with the HIV-1 virus, a two-domain model is proposed that separates HIV-1 into a stable non-proliferating domain where the virus is integrated into the host resting memory CD4+ t cells; and, a second domain where the virus is in the blood in a rapidly reproductive state. ART inhibits blood HIV-1 reproduction levels sufficient to prevent progression to the AIDS end-stage, the principal goal of ART. There are 25 FDA approved antiretroviral drugs toward this goal grouped into 6 classes: NRTIs (nucleoside/nucleotide inhibitors), NNRTIs (non-nucleoside/nucleotide inhibitors), PIs (protease inhibitors), FIs (fusion inhibitors), CCR5s (chemokine cell receptor 5 antagonists), and INSTIs (integrase inhibitors)...
August 3, 2018: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/30058430/evaluation-of-the-concentrations-of-psychotropic-drugs-in-hiv-infected-versus-hiv-negative-patients-potential-implications-for-clinical-practice
#8
Dario Cattaneo, Sara Baldelli, Chiara Resnati, Andrea Giacomelli, Paola Meraviglia, Davide Minisci, Noemi Astuti, Annalisa Ridolfo, Giuseppe V De Socio, Emilio Clementi, Massimo Galli, Cristina Gervasoni
OBJECTIVES: The management of psychiatric illness in HIV-infected patients is clinically challenging because of the risk of potential drug-drug interactions. Here, we aimed to measure the antidepressant and/or antipsychotic drug concentrations in HIV-infected patients during routine outpatient visits. METHODS: Six hundred HIV-infected patients were screened during the first 15 months after the introduction of our outpatient polytherapy management service in a search for subjects treated with psychotropic drugs for at least three months...
July 30, 2018: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/30052493/the-human-immunodeficiency-virus-capsid-is-more-than-just-a-genome-package
#9
Leo C James, David A Jacques
Human immunodeficiency virus (HIV) is one of the most studied of all human pathogens. One strain-HIV-1 group M-is responsible for a global pandemic that has infected >60 million people and killed >20 million. Understanding the stages of HIV infection has led to highly effective therapeutics in the form of antiviral drugs that target the viral enzymes reverse transcriptase, integrase, and protease as well as biotechnological developments in the form of retroviral and lentiviral vectors for the transduction of cells in tissue culture and, potentially, gene therapy...
July 27, 2018: Annual Review of Virology
https://www.readbyqxmd.com/read/30051758/exploring-the-drug-resistance-mechanism-of-active-site-non-active-site-mutations-and-their-cooperative-effects-in-crf01_ae-hiv-1-protease-molecular-dynamics-simulations-and-free-energy-calculations
#10
Vasavi C S, Tamizhselvi Ramasamy, Punnagai Munusami
Human immunodeficiency virus type 1 protease is essential for virus replication and maturation and has been considered as one of the important drug target for the antiretroviral treatment of HIV infection. The majority of HIV infections are caused due to non-B subtypes in developing countries. Subtype AE is spreading rapidly and infecting huge population worldwide. Understanding the interdependence of active and non-active site mutations in conferring drug resistance is crucial for the development effective inhibitors in subtype AE protease...
July 27, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/30047573/using-safe-affordable-and-accessible-non-steroidal-anti-inflammatory-drugs-to-reduce-the-number-of-hiv-target-cells-in-the-blood-and-at-the-female-genital-tract
#11
Julie Lajoie, Kenzie Birse, Lucy Mwangi, Yufei Chen, Juliana Cheruiyot, Maureen Akolo, John Mungai, Genevieve Boily-Larouche, Laura Romas, Sarah Mutch, Makobu Kimani, Julius Oyugi, Emmanuel A Ho, Adam Burgener, Joshua Kimani, Keith R Fowke
INTRODUCTION: At its basic level, HIV infection requires a replication-competent virus and a susceptible target cell. Elevated levels of vaginal inflammation has been associated with the increased risk of HIV infection as it brings highly activated HIV target cells (CCR5+CD4+ T cells; CCR5+CD4+CD161+ Th17 T cells) to the female genital tract (FGT) where they interact with HIV. Decreased HIV risk has been associated with a phenotype of decreased immune activation, called immune quiescence, described among Kenyan female sex workers who were intensely exposed to HIV yet remain uninfected...
July 2018: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/30047107/clinical-pharmacokinetics-and-drug-interactions-of-doravirine
#12
Kyle John Wilby, Nesma Ahmed Eissa
Doravirine is a new HIV-1 non-nucleoside reverse transcriptase inhibitor that has demonstrated a good efficacy and safety profile in clinical trials. It has a therapeutic profile that makes it an attractive option for treatment of HIV-1 infection. As such, there has been an increase in the published literature regarding the pharmacokinetics of doravirine and potential for drug-drug interactions. This review aimed to identify pharmacokinetic literature pertaining to doravirine, used findings from the literature to summarize its pharmacokinetic profile, and finally evaluated literature describing actual and potential drug interactions...
July 25, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/30045416/treatment-for-hiv-associated-cryptococcal-meningitis
#13
REVIEW
Mark W Tenforde, Adrienne E Shapiro, Benjamin Rouse, Joseph N Jarvis, Tianjing Li, Ingrid Eshun-Wilson, Nathan Ford
BACKGROUND: Cryptococcal meningitis is a severe fungal infection that occurs primarily in the setting of advanced immunodeficiency and remains a major cause of HIV-related deaths worldwide. The best induction therapy to reduce mortality from HIV-associated cryptococcal meningitis is unclear, particularly in resource-limited settings where management of drug-related toxicities associated with more potent antifungal drugs is a challenge. OBJECTIVES: To evaluate the best induction therapy to reduce mortality from HIV-associated cryptococcal meningitis; to compare side effect profiles of different therapies...
July 25, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/30044217/structural-basis-for-potent-and-broad-inhibition-of-hiv-1-rt-by-thiophene-3-2-d-pyrimidine-non-nucleoside-inhibitors
#14
Yang Yang, Dongwei Kang, Laura A Nguyen, Zachary B Smithline, Christophe Pannecouque, Peng Zhan, Xinyong Liu, Thomas A Steitz
Rapid generation of drug-resistant mutations in HIV-1 reverse transcriptase (RT), a prime target for anti-HIV therapy, poses a major impediment to effective anti-HIV treatment. Our previous efforts have led to the development of two novel non-nucleoside reverse transcriptase inhibitors (NNRTIs) with piperidine-substituted thiophene[3,2- d ]pyrimidine scaffolds, compounds K-5a2 and 25a, which demonstrate highly potent anti-HIV-1 activities and improved resistance profiles compared with etravirine and rilpivirine, respectively...
July 25, 2018: ELife
https://www.readbyqxmd.com/read/30040330/-hiv-positive-patients-visit-an-increasing-number-of-physicians
#15
Karlijn Groen, Suzanne E Geerlings
The population of people living with HIV is ageing. As a result, an increasing proportion of people on combination antiretroviral therapy will experience comorbidities and polypharmacy, with the risk of drug-drug interactions. These comorbidities will also be treated by physicians who are not specialised in HIV. Moreover, early diagnosis and treatment improve the prognosis of HIV infection, but 11% of the people living with HIV are currently undiagnosed. Therefore, physicians should be alert to the possibility of HIV also with regard to older adults...
July 6, 2018: Nederlands Tijdschrift Voor Geneeskunde
https://www.readbyqxmd.com/read/30037382/-antiretroviral-hiv-therapy-and-hormonal-contraceptives
#16
Kristina Thorsteinsson, Anne-Mette Lebech, Kim Peder Dalhoff, Charlotte Wilken-Jensen, Terese Lea Katzenstein
HIV guidelines recommend assessment of conception issues for all people living with HIV. Studies have shown negligible risk of HIV transmission from well-treated patients with HIV, and therefore condoms are no longer recom-mended to reduce HIV transmission. Some antiretroviral agents are metabolised through the same enzyme systems in the liver as hormonal contraceptives, which can affect the plasma concentration of both drug classes and the effect of the drugs, including reduced contraceptive efficacy. This review discusses the interactions between antiretroviral agents and hormonal contraceptives...
July 23, 2018: Ugeskrift for Laeger
https://www.readbyqxmd.com/read/30029487/antiviral-compounds-from-myxobacteria
#17
REVIEW
Lucky S Mulwa, Marc Stadler
Viral infections including human immunodeficiency virus (HIV), cytomegalovirus (CMV), hepatitis B virus (HBV), and hepatitis C virus (HCV) pose an ongoing threat to human health due to the lack of effective therapeutic agents. The re-emergence of old viral diseases such as the recent Ebola outbreaks in West Africa represents a global public health issue. Drug resistance and toxicity to target cells are the major challenges for the current antiviral agents. Therefore, there is a need for identifying agents with novel modes of action and improved efficacy...
July 19, 2018: Microorganisms
https://www.readbyqxmd.com/read/30011391/endotoxin-modulates-the-expression-of-renal-drug-transporters-in-hiv-1-transgenic-rats
#18
Navaz Karimian Pour, Micheline Piquette-Miller
PURPUSE: Bacterial co-infections and low grade endotoxemia are common in HIV patients. Inflammation due to endotoxin or HIV may influence the expression and activity of transporters. Kidney transporters influence renal drug clearances including many antiretroviral agents. Our objective was to study the effect of endotoxin and HIV on the renal expression of drug transporters in an HIV-transgenic (HIV-Tg) rat model. These rats develop immune dysfunction and AIDS-associated conditions like humans...
2018: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/30006027/building-competencies-to-prevent-youth-substance-use-in-kazakhstan-mixed-methods-findings-from-a-pilot-family-focused-multimedia-trial
#19
Leyla Ismayilova, Assel Terlikbayeva
PURPOSE: The knowledge-based approach to substance use and HIV prevention, commonly used in CentralAsia, does not equip at-risk adolescents with risk reduction skills. This pilot study aims to adapt and test the feasibility and estimate the effect size parameters of a skill-based and family-focused intervention for at-risk adolescents from communities affected by heroin trade and use in Kazakhstan, located on the major drug trafficking route from Afghanistan. METHODS: This National Institute on Drug Abuse-funded pilot trial used a mixed-methods approach and included 181 adolescents (ages 14-17) that reported at least one risk factor (e...
July 10, 2018: Journal of Adolescent Health: Official Publication of the Society for Adolescent Medicine
https://www.readbyqxmd.com/read/30003668/exploring-the-flap-dynamics-of-the-south-african-hiv-subtype-c-protease-in-presence-of-fda-approved-inhibitors-md-study
#20
Siyabonga I Maphumulo, Amit K Halder, Thavendran Govender, Sibusiso Maseko, Glenn E M Maguire, Bahareh Honarparvar, Hendrik G Kruger
HIV-1 protease (HIV PR) is considered one of the most attractive targets for the treatment of HIV and the impact of flap dynamics of HIV PR on the binding affinities of protease inhibitors (PIs) is one of the crucial ongoing research field. Recently, our research group evaluated the binding affinities of different FDA approved PIs against the South African HIV-1 subtype C (C-SA) protease (PR). The CSA- HIV PR displayed weaker binding affinity for most of the clinical PIs compared to HIV-1 B subtype for West and Central Europe, the Americas...
July 13, 2018: Chemical Biology & Drug Design
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