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https://www.readbyqxmd.com/read/30534615/relationship-between-hiv-integrase-polymorphisms-and-integrase-inhibitor-susceptibility-an-in-silico-analysis
#1
Hotma Martogi Lorensi Hutapea, Yustinus Maladan, Widodo
Integrase (IN) plays an essential role in HIV-1 replication, by mediating integration of the viral genome into the host cell genome. IN is a potential target of antiretroviral (ARV) therapeutic drugs such as ALLINI, Raltegravir (RAL), and Elvitegravir (EVG). The effect of IN polymorphisms on its structure and binding affinity to the integrase inhibitors (INIs) is not well understood. The goal of this study was to examine the effect of IN polymorphisms on its tertiary structure and binding affinities to INIs using computational approaches...
December 2018: Heliyon
https://www.readbyqxmd.com/read/30532532/regulation-of-in-vivo-behavior-of-tat-modified-liposome-by-associated-protein-corona-and-avidity-to-tumor-cells
#2
Mohamadreza Amin, Mahsa Bagheri, Mercedeh Mansourian, Mahmoud Reza Jaafari, Timo Lm Ten Hagen
Introduction: PEGylated liposomes are widely used and studied as carriers for chemotherapeutics. While pharmacokinetics of the encapsulated drug is drastically altered resulting in favorable circulation time, improved tumor accumulation, and better manageable or reduced side effects, therapeutic efficacy has been disappointing. Major drawbacks are a failure to reach the tumor cell, limited penetration depth, and impaired uptake by tumor cells. Materials and methods: Here, we study the implication of HIV-1 transactivator of transcription (TAT)-derived peptides inserted on PEGylated liposomal doxorubicin (PLD) and followed in vitro and in vivo fate...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/30530702/microed-structures-of-hiv-1-gag-ctd-sp1-reveal-binding-interactions-with-the-maturation-inhibitor-bevirimat
#3
Michael D Purdy, Dan Shi, Jakub Chrustowicz, Johan Hattne, Tamir Gonen, Mark Yeager
HIV-1 protease (PR) cleavage of the Gag polyprotein triggers the assembly of mature, infectious particles. Final cleavage of Gag occurs at the junction helix between the capsid protein CA and the SP1 spacer peptide. Here we used MicroED to delineate the binding interactions of the maturation inhibitor bevirimat (BVM) using very thin frozen-hydrated, 3D microcrystals of a CTD-SP1 Gag construct with and without bound BVM. The 2.9-Å MicroED structure revealed that a single BVM molecule stabilizes the six-helix bundle via both electrostatic interactions with the dimethylsuccinyl moiety and hydrophobic interactions with the pentacyclic triterpenoid ring...
December 10, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/30529029/lopinavir-ritonavir-super-boosting-in-young-hiv-infected-children-on-rifampicin-based-tuberculosis-therapy-compared-with-lopinavir-ritonavir-without-rifampicin-a-pharmacokinetic-modelling-and-clinical-study
#4
Helena Rabie, Paolo Denti, Janice Lee, Mhleli Masango, Ashraf Coovadia, Sandy Pillay, Afaaf Liberty, François Simon, Helen McIlleron, Mark F Cotton, Marc Lallemant
BACKGROUND: Rifampicin reduces lopinavir concentrations in HIV and tuberculosis co-treated patients. We hypothesised that adding ritonavir to co-formulated lopinavir-ritonavir (4:1) to achieve a one-to-one ratio would overcome this drug-drug interaction in young children. METHODS: We did a prospective, open-label, one-group, one-sequence study at five sites in three South African provinces. We included HIV-infected children with tuberculosis, a bodyweight of 3-15 kg, and a post-conceptional age of more than 42 weeks...
December 6, 2018: Lancet HIV
https://www.readbyqxmd.com/read/30524704/clozapine-hiv-and-neutropenia-a-case-report
#5
Eromona Whiskey, David O'Flynn, David Taylor
There is paucity of information on the use of clozapine in patients with HIV. Ethnicity, co-prescribed medications and possible drug-drug interactions are important considerations in evaluating risk of blood dyscrasias during clozapine treatment. Individuals with HIV should not be denied access to the most effective antipsychotic, but a multidisciplinary approach is essential for optimal outcome in such complex patients.
December 2018: Therapeutic Advances in Psychopharmacology
https://www.readbyqxmd.com/read/30522620/time-to-sputum-culture-conversion-and-treatment-outcome-among-the-first-cohort-of-multidrug-resistant-tuberculosis-patients-in-a-high-burden-country
#6
O M Ige, Regina E Oladokun
BACKGROUND: Sputum conversion considered the most important interim indicator of the efficacy of anti-tuberculosis treatment was assessed at varying time points among the first cohort of multidrug resistant tuberculosis (MDR-TB) patients in a National TB Control Programme. METHODS: A retrospective study was conducted for the period between 2010 and 2013, at the premiere MDR-TB treatment center in Nigeria. Genexpert, culture and drug susceptibility tests were carried out...
October 2018: Indian Journal of Tuberculosis
https://www.readbyqxmd.com/read/30522451/mortality-recurrent-seizure-risk-after-new-onset-seizure-in-hiv-positive-zambian-adults
#7
Melissa A Elafros, Brent A Johnson, Omar K Siddiqi, Jason F Okulicz, Izukanji Sikazwe, Christopher M Bositis, Michael J Potchen, Igor J Koralnik, William H Theodore, Lisa Kalungwana, Gretchen L Birbeck
BACKGROUND: Recurrent seizure risks in HIV-positive people with new-onset seizure are largely unknown, making it challenging to offer optimal recommendations regarding antiepileptic drug (AED) initiation. Existing outcomes data is limited, and risk factor identification requires a diagnostic assessment, which is often unavailable in regions heavily effected by HIV, like sub-Saharan Africa. METHODS: HIV-positive Zambian adults with new-onset seizure were enrolled in a prospective cohort study to determine seizure recurrence and risk factors for recurrence...
December 7, 2018: BMC Neurology
https://www.readbyqxmd.com/read/30521534/molecular-epidemiology-of-hiv-1-infection-among-men-who-have-sex-with-men-in-taiwan-from-2013-to-2015
#8
Wei-You Li, Marcelo Chen, Szu-Wei Huang, I-An Jen, Sheng-Fan Wang, Jyh-Yuan Yang, Yen-Hsu Chen, Yi-Ming Arthur Chen
Men who have sex with men (MSM) is the major risk population of HIV-1 infection in Taiwan, and its surveillance has become critical in HIV-1 prevention. We recruited MSM subjects from 17 high-risk venues and 4 community centers in northern and southern Taiwan for anonymous HIV-1 screening during 2013-2015. Blood samples were obtained for genotyping and phylogenetic analysis, and a questionnaire survey covering demographic variables and social behavior was conducted. In total, 4,675 subjects were enrolled, yielding a HIV-1 prevalence rate of 4...
2018: PloS One
https://www.readbyqxmd.com/read/30513600/identification-of-diaryl-quinoline-compounds-as-entry-inhibitors-of-ebola-virus
#9
Qinghua Cui, Han Cheng, Rui Xiong, Gang Zhang, Ruikun Du, Manu Anantpadma, Robert A Davey, Lijun Rong
Ebola virus is the causative agent of Ebola virus disease in humans. The lethality of Ebola virus infection is about 50%, supporting the urgent need to develop anti-Ebola drugs. Glycoprotein (GP) is the only surface protein of the Ebola virus, which is functionally critical for the virus to attach and enter the host cells, and is a promising target for anti-Ebola virus drug development. In this study, using the recombinant HIV-1/Ebola pseudovirus platform we previously established, we evaluated a small molecule library containing various quinoline compounds for anti-Ebola virus entry inhibitors...
November 30, 2018: Viruses
https://www.readbyqxmd.com/read/30513108/raltegravir-intensified-initial-antiretroviral-therapy-in-advanced-hiv-disease-in-africa-a-randomised-controlled-trial
#10
Cissy Kityo, Alexander J Szubert, Abraham Siika, Robert Heyderman, Mutsa Bwakura-Dangarembizi, Abbas Lugemwa, Shalton Mwaringa, Anna Griffiths, Immaculate Nkanya, Sheila Kabahenda, Simon Wachira, Godfrey Musoro, Chatu Rajapakse, Timothy Etyang, James Abach, Moira J Spyer, Priscilla Wavamunno, Linda Nyondo-Mipando, Ennie Chidziva, Kusum Nathoo, Nigel Klein, James Hakim, Diana M Gibb, A Sarah Walker, Sarah L Pett
BACKGROUND: In sub-Saharan Africa, individuals infected with HIV who are severely immunocompromised have high mortality (about 10%) shortly after starting antiretroviral therapy (ART). This group also has the greatest risk of morbidity and mortality associated with immune reconstitution inflammatory syndrome (IRIS), a paradoxical response to successful ART. Integrase inhibitors lead to significantly more rapid declines in HIV viral load (VL) than all other ART classes. We hypothesised that intensifying standard triple-drug ART with the integrase inhibitor, raltegravir, would reduce HIV VL faster and hence reduce early mortality, although this strategy could also risk more IRIS events...
December 2018: PLoS Medicine
https://www.readbyqxmd.com/read/30510106/methamphetamine-impairs-igg1-mediated-phagocytosis-and-killing-of-cryptococcus-neoformans-by-j774-16-macrophage-and-nr-9640-microglia-like-cells
#11
Lilit Aslanyan, Hiu H Lee, Vaibhav V Ekhar, Raddy L Ramos, Luis R Martinez
The prevalence of methamphetamine (METH) use is estimated at ∼35 million people worldwide, with over 10 million users in the United States. Chronic METH abuse and dependence expose the users to participate in risky behaviors that may result in the acquisition of HIV and AIDS-related infections. Cryptococcus neoformans is an encapsulated fungus that causes cryptococcosis, an opportunistic infection that has recently been associated with drug users. METH enhances C. neoformans pulmonary infection, facilitating its dissemination and penetration to the central nervous system in mice...
December 3, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/30509315/correlates-of-hiv-infection-among-transgender-women-in-two-chinese-cities
#12
Duo Shan, Mao-He Yu, Jie Yang, Ming-Hua Zhuang, Zhen Ning, Hui Liu, Lu Liu, Meng-Jie Han, Da-Peng Zhang
BACKGROUND: In an era when HIV transmission has been on the rise among men who have sex with men (MSM), transgender women may play a considerable role in China's current HIV epidemic as a potential "bridge" of HIV transmission between homosexual and heterosexual populations. We sought to understand the risk behaviours and factors associated with HIV infection among transgender women in two cities in China. METHODS: From January to December 2016, we recruited transgender women with the help of community-based organizations (CBOs) through a wide range of methods, including snowball sampling...
December 1, 2018: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/30506751/an-in-silico-pharmacological-approach-toward-the-discovery-of-potent-inhibitors-to-combat-drug-resistance-hiv-1-protease-variants
#13
Chirasmita Nayak, Ishwar Chandra, Sanjeev Kumar Singh
Protease inhibitors (PIs) are crucial drugs in highly active antiretroviral therapy for human immunodeficiency virus-1 (HIV-1) infections. However, resistance owing to mutations challenge the long-term efficacy in the medication of HIV-1-infected individuals. Lopinavir (LPV) and darunavir (DRV), two second-generation drugs are the most potent among PIs, hustling the drug resistance when mutations occur in the active and nonactive site of the protease (PR). Herein, we strive for compounds that can stifle the function of wild-type (WT) HIV-1 PR along with four major single mutants (I54M, V82T, I84V, and L90M) instigating resistance to the PIs using in silico approach...
December 3, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/30499404/antimalarials-review-of-plasmepsins-as-drug-targets-and-hiv-protease-inhibitors-interactions
#14
Whelton A Miller, Joshua Teye, Angela O Achieng, Reagan M Mogire, Hoseah Akala, John M Ong'cha, Brijesh Rathi, Ravi Durvasula, Prakasha Kempaiah, Samuel K Kwofie
Malaria is a major global health concern with majority of cases reported in regions of South-East Asia, Eastern Mediterranean, Western Pacific, the Americas, and Sub-Saharan Africa. The World Health Organization (WHO) estimated 216 million worldwide reported cases of malaria in 2016. It is an infection of the red blood cells by parasites of the genus Plasmodium with most severe and common forms caused by Plasmodium falciparum (P. falciparum or Pf) and Plasmodium vivax (P. vivax or Pv). Emerging parasite resistance to available antimalarial drugs poses great challenges to treatment...
November 30, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/30480761/mefloquine-for-preventing-malaria-in-pregnant-women
#15
REVIEW
Raquel González, Clara Pons-Duran, Mireia Piqueras, John J Aponte, Feiko O Ter Kuile, Clara Menéndez
BACKGROUND: The World Health Organization recommends intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine for malaria for all women who live in moderate to high malaria transmission areas in Africa. However, parasite resistance to sulfadoxine-pyrimethamine has been increasing steadily in some areas of the region. Moreover, HIV-infected women on cotrimoxazole prophylaxis cannot receive sulfadoxine-pyrimethamine because of potential drug interactions. Thus, there is an urgent need to identify alternative drugs for prevention of malaria in pregnancy...
November 14, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/30479300/contextual-factors-associated-with-consistent-condom-use-and-condom-self-efficacy-amongst-african-asylum-seekers-and-refugees-in-hong-kong
#16
William Chi Wai Wong, Sealing Cheng, Heidi Yin Hai Miu, Jason J Ong, Julie Chen, Kelley Ann Loper
BACKGROUND: Hong Kong has no systematic domestic policies committed to the rights of asylum-seekers and refugees (ASRs). This study explores the sexual health behaviours and social inequities amongst African ASRs in Hong Kong. METHODS: A cross-sectional survey of African ASRs was conducted through three local non-governmental organizations in 2013. A logistic model was used to test the interactions and relationship between the respondents' consistent condom use and contextual antecedents, socio-demographic factors, psychosocial factors and condom self-efficacy (CSE) score...
March 2018: Infection, disease & health
https://www.readbyqxmd.com/read/30475425/esrd-patients-coinfected-with-human-immunodeficiency-virus-and-hepatitis-c-outcomes-and-management-challenges
#17
Deirdre Sawinski
HIV infection is a major public health problem worldwide. Due to shared modes of acquisition, many HIV+ patients are coinfected with Hepatitis C. HIV/HCV coinfected patients have an increased burden of chronic kidney disease and are more likely to progress to end-stage renal disease. Dialysis survival is diminished in the coinfected population, even in the contemporary era. Kidney transplantation offers a survival benefit over remaining on dialysis; however, posttransplant outcomes are inferior compared to patients with HIV infection alone...
November 26, 2018: Seminars in Dialysis
https://www.readbyqxmd.com/read/30471555/nutraceutical-treatment-for-hypercholesterolemia-in-hiv-infected-patients-the-nu-try-hiv-randomized-cross-over-trial
#18
Matteo Pirro, Daniela Francisci, Vanessa Bianconi, Elisabetta Schiaroli, Massimo R Mannarino, Francesco Barsotti, Andrea Spinozzi, Francesco Bagaglia, Amirhossein Sahebkar, Franco Baldelli
BACKGROUND AND AIMS: Despite hypercholesterolemia has been recognized to increase cardiovascular risk in human immunodeficiency virus (HIV)-infected patients, cholesterol-lowering therapy is underused in this population, due to fear of drug-drug interactions with antiretroviral therapy (ART). We investigated the effects of a nutraceutical combination (NC) on lipid profile, proprotein convertase subtilisin/kexin type 9 (PCSK9), subclinical inflammation and arterial stiffness in ART-treated HIV-infected patients...
November 14, 2018: Atherosclerosis
https://www.readbyqxmd.com/read/30471138/pharmacogenetics-of-artemether-lumefantrine-influence-on-nevirapine-disposition-clinically-significant-drug-drug-interaction
#19
Sa'ad T Abdullahi, Adeniyi Olagunju, Julius O Soyinka, Rahman A Bolarinwa, Olusola J Olarewaju, Moji T Bakare-Odunola, Andrew Owen, Saye Khoo
AIMS: In this study the influence of first-line antimalarial drug artemether-lumefantrine on the pharmacokinetics of the antiretroviral drug nevirapine was investigated in the context of selected single nucleotide polymorphisms (SNPs) in a cohort of adult HIV-infected Nigerian patients. METHODS: This was a two-period, single sequence crossover study conducted in two stages. In stage 1, 150 HIV-infected patients receiving nevirapine-based antiretroviral regimens were enrolled and genotyped for 7 SNPs...
November 24, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/30464642/dolutegravir-rilpivirine-for-the-treatment-of-hiv-1-infection
#20
REVIEW
Ellen Dowers, Francis Zamora, Lydia Aoun Barakat, Onyema Ogbuagu
Much progress has been made in the development of antiretroviral therapies (ARTs) for HIV-1 infection. Beginning a little over a decade ago, single tablet combination regimens (STRs) became available, and subsequently, newer STR formulations with improved safety profiles have emerged. Recently, there is a growing interest in regimen simplification with the primary goal of further reducing long-term toxicities of ART and improving medication adherence. Dolutegravir/rilpivirine (DTG/RPV) was approved by the US Food and Drug Administration (FDA) as the first dual antiretroviral STR for the maintenance therapy of HIV-1 infection...
2018: HIV/AIDS: Research and Palliative Care
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