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Hiv drug resistance

Xia Jin, Hua Xu, Michael S McGrath
Monocyte activation and polarization play essential roles in many chronic inflammatory diseases. An imbalance of M1 and M2 macrophage activation (pro-inflammatory and alternatively activated, respectively) is believed to be a key aspect in the etiology of these diseases, thus a therapeutic approach that regulates macrophage activation could be of broad clinical relevance. Methylglyoxal-bis-guanylhydrazone (MGBG), a regulator of polyamine metabolism, has recently been shown to be concentrated in monocytes and macrophages, and interfere with HIV integration into the DNA of these cells in vitro...
2018: PloS One
Xiujuan Zhang, Yuanmei Zhu, Hao Hu, Senyan Zhang, Pengfei Wang, Huihui Chong, Jinsheng He, Xinquan Wang, Yuxian He
The deep hydrophobic pocket of HIV-1 gp41 has been considered a drug target, but short-peptides targeting this site usually lack potent antiviral activity. By applying the M-T hook structure, we previously generated highly potent short-peptide fusion inhibitors that specifically targeted the pocket site, such as MT-SC22EK, HP23L, and LP-11. Here, the crystal structures of HP23L and LP-11 bound to the target mimic peptide N36 demonstrated the critical intrahelical and interhelical interactions, especially verifying that the hook-like conformation was finely adopted while the methionine residue was replaced by the oxidation-less prone residue leucine, and that addition of an extra glutamic acid significantly enhanced the binding and inhibitory activities...
2018: Frontiers in Cellular and Infection Microbiology
George W Pratt, Andy Fan, Bissrat Melakeberhan, Catherine M Klapperich
Proper management of an HIV infection requires that a patient be at least 80-95% adherent to a prescribed drug regimen to avoid poor health outcomes and the development of drug-resistant HIV strains. Clinicians generally monitor adherence habits indirectly through patient self-reporting, pill counting, and electronic drug monitoring. While direct measurement of patient samples like urine for monitoring drug levels is possible, it requires specialized equipment and training that is not readily available in resource-limited settings where the need is greatest...
August 9, 2018: Analytica Chimica Acta
M Chen, M H Jia, Y L Ma, H B Luo, H C Chen, C J Yang, J Dai, L Yang, L J Dong, R Lu, L J Song, Y Han, J Y Lu, A K L Cheung, Z W Chen, L Lu
Multiple human immunodeficiency virus (HIV)-1 genotypes in China were first discovered in Yunnan Province before disseminating throughout the country. As the HIV-1 epidemic continues to expand in Yunnan, genetic characteristics and transmitted drug resistance (TDR) should be further investigated among the recently infected population. Among 2828 HIV-positive samples newly reported in the first quarter of 2014, 347 were identified as recent infections with BED-captured enzyme immunoassay (CEIA). Of them, 291 were successfully genotyped and identified as circulating recombinant form (CRF)08_BC (47...
March 14, 2018: Epidemiology and Infection
Joy Y Feng
Nucleoside and nucleotide analogs have played significant roles in antiviral therapies and are valued for their impressive potency and high barrier to resistance. They have been approved for treatment of herpes simplex virus-1, HIV, HBV, HCV, and influenza, and new drugs are being developed for the treatment of RSV, Ebola, coronavirus MERS, and other emerging viruses. However, this class of compounds has also experienced a high attrition rate in clinical trials due to toxicity. In this review, we discuss the utility of different biochemical and cell-based assays and provide recommendations for assessing toxicity liability before entering animal toxicity studies...
January 2018: Antiviral Chemistry & Chemotherapy
Dimitrios Pilalas, Lemonia Skoura, Apostolia Margariti, Fani Chatzopoulou, Dimitrios Chatzidimitriou, Olga Tsachouridou, Pantelis Zebekakis, Simeon Metallidis, Maria Papaioannou
OBJECTIVES: Despite successful virological suppression, HIV transcription frequently persists intracellularly. In this study, we hypothesize that HIV persistent transcription(HIVpt) may affect to a different extent patients on stable efavirenz(EFV) versus atazanavir(ATV)-based regimens. The role of the expression of drug efflux transporters in HIVpt was also investigated. METHODS: We prospectively enrolled 51 virologically suppressed patients on first-line treatment for one year with EFV or ATV combined with emtricitabine and tenofovir and followed them up for one year...
2018: PloS One
Sonia de Castro, María-José Camarasa
HIV infection still has a serious health and socio-economical impact and is one of the primary causes of morbidity and mortality all over the world. HIV infection and the AIDS pandemic are still matters of great concern, especially in less developed countries where the access to highly active antiretroviral therapy (HAART) is limited. Patient compliance is another serious drawback. Nowadays, HAART is the treatment of choice although it is not the panacea. Despite the fact that it suppresses viral replication at undetectable viral loads and prevents progression of HIV infection into AIDS HAART has several pitfalls, namely, long-term side-effects, drug resistance development, emergence of drug-resistant viruses, low compliance and the intolerance of some patients to these drugs...
March 5, 2018: European Journal of Medicinal Chemistry
Abid Qureshi, Akanksha Rajput, Gazaldeep Kaur, Manoj Kumar
A number of anti-retroviral drugs are being used for treating Human Immunodeficiency Virus (HIV) infection. Due to emergence of drug resistant strains, there is a constant quest to discover more effective anti-HIV compounds. In this endeavor, computational tools have proven useful in accelerating drug discovery. Although methods were published to design a class of compounds against a specific HIV protein, but an integrated web server for the same is lacking. Therefore, we have developed support vector machine based regression models using experimentally validated data from ChEMBL repository...
March 9, 2018: Journal of Cheminformatics
Nico Holmstock, Marlies Oorts, Jan Snoeys, Pieter Annaert
Hepatic drug transporters play a pivotal role in the excretion of drugs from the body, in drug-drug interactions as well as in drug-induced liver toxicity. Hepatocytes cultured in sandwich configuration are an advantageous model to investigate the interactions of drug candidates with apical efflux transporters in a bio-relevant manner. However, the commonly used 'offline' assays (i.e. that rely on measuring intracellular accumulated amounts after cell lysis) are time and resource consuming while data output is often high and variable...
March 9, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Oksana Pasechnik, Anna Vyazovaya, Stanislav Vitriv, Marina Tatarintseva, Aleksey Blokh, Vladimir Stasenko, Igor Mokrousov
This population-based study characterized Mycobacterium tuberculosis isolates from HIV-positive and HIV-negative tuberculosis (TB) patients in the Omsk region in Western Siberia, Russia. We sought to gain insight into the major genotype families and epidemic and endemic clones of M. tuberculosis in the area with a high burden and adverse trend of TB/HIV coinfection. The study collection included M. tuberculosis isolates from 207 newly-diagnosed patients with pulmonary TB; 55 (26.5%) of patients were HIV-infected...
January 2018: Tuberculosis
Payal Dande, Purva Samant
Tuberculosis [TB] has afflicted numerous nations in the world. As per a report by the World Health Organization [WHO], an estimated 1.4 million TB deaths in 2015 and an additional 0.4 million deaths resulting from TB disease among people living with HIV, were observed. Most of the TB deaths can be prevented if it is detected at an early stage. The existing processes of diagnosis like blood tests or sputum tests are not only tedious but also take a long time for analysis and cannot differentiate between different drug resistant stages of TB...
January 2018: Tuberculosis
V T Valuev-Elliston, S N Kochetkov
Highly active antiretroviral therapy (HAART) is one of the most effective means for fighting against HIV-infection. HAART primarily targets HIV-1 reverse transcriptase (RT), and 14 of 28 compounds approved by the FDA as anti-HIV drugs act on this enzyme. HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) hold a special place among HIV RT inhibitors owing to their high specificity and unique mode of action. Nonetheless, these drugs show a tendency to decrease their efficacy due to high HIV-1 variability and formation of resistant virus strains tolerant to clinically applied HIV NNRTIs...
December 2017: Biochemistry. Biokhimii︠a︡
Wenwen Dai, Yu Wu, Jinpeng Bi, Shuai Wang, Fang Li, Wei Kong, Julien Barbier, Jean-Christophe Cintrat, Feng Gao, Daniel Gillet, Weiheng Su, Chunlai Jiang
Herpes simplex virus type 2 (HSV-2) is the causative pathogen of genital herpes and is closely associated with the occurrence of cervical cancer and human immunodeficiency virus (HIV) infection. The absence of an effective vaccine and the emergence of drug resistance to commonly used nucleoside analogs emphasize the urgent need for alternative antivirals against HSV-2. Recently, ABMA [1-adamantyl (5-bromo-2-methoxybenzyl) amine] has been demonstrated to be an inhibitor of several pathogens exploiting host-vesicle transport, which also participates in the HSV-2 lifecycle...
March 9, 2018: Viruses
Mathieu Bastard, Elisabeth Sanchez-Padilla, Philipp du Cros, Atadjan Karimovich Khamraev, Nargiza Parpieva, Mirzagaleg Tillyashaykov, Armen Hayrapetyan, Kamene Kimenye, Shazina Khurkhumal, Themba Dlamini, Santiago Fadul Perez, Alex Telnov, Cathy Hewison, Francis Varaine, Maryline Bonnet
BACKGROUND: The emergence of resistance to anti-tuberculosis (DR-TB) drugs and the HIV epidemic represent a serious threat for reducing the global burden of TB. Although data on HIV-negative DR-TB treatment outcomes are well published, few data on DR-TB outcomes among HIV co-infected people is available despite the great public health importance. METHODS: We retrospectively reported and compared the DR-TB treatment outcomes of HIV-positive and HIV-negative patients treated with an individualized regimen based on WHO guidelines in seven countries: Abkhazia, Armenia, Colombia, Kenya, Kyrgyzstan, Swaziland and Uzbekistan...
2018: PloS One
Elizabeth A Ashley, Judith Recht, Arlene Chua, David Dance, Mehul Dhorda, Nigel V Thomas, Nisha Ranganathan, Paul Turner, Philippe J Guerin, Nicholas J White, Nicholas P Day
Low- and middle-income countries (LMICs) shoulder the bulk of the global burden of infectious diseases and drug resistance. We searched for supranational networks performing antimicrobial resistance (AMR) surveillance in LMICs and assessed their organization, methodology, impacts and challenges. Since 2000, 72 supranational networks for AMR surveillance in bacteria, fungi, HIV, TB and malaria have been created that have involved LMICs, of which 34 are ongoing. The median (range) duration of the networks was 6 years (1-70) and the number of LMICs included was 8 (1-67)...
March 5, 2018: Journal of Antimicrobial Chemotherapy
Hua-Xin Zhang, Dan Zhou, Qing-Hua Xia
In this work, the interaction of an anti-HIV drug lamivudine and human serum albumin (HSA) was studied by multispectroscopic and molecular modeling methods. The fluorescence emission spectra showed that the fluorescence of HSA was quenched by lamivudine through static mechanism with HSA-lamivudine complex produced at ground state. According to the binding equilibriums observed at 4 different temperatures, the number of binding site, binding constant, enthalpy change, entropy change, and Gibbs free energy change of the interaction were calculated...
March 7, 2018: Journal of Molecular Recognition: JMR
Manabu Aoki, Debananda Das, Hironori Hayashi, Hiromi Aoki-Ogata, Yuki Takamatsu, Arun K Ghosh, Hiroaki Mitsuya
Darunavir (DRV) has bimodal activity against HIV-1 protease, enzymatic inhibition and protease dimerization inhibition, and has an extremely high genetic barrier against development of drug resistance. We previously generated a highly DRV-resistant HIV-1 variant (HIVDRV R P51 ). We also reported that four amino acid substitutions (V32I, L33F, I54M, and I84V) identified in the protease of HIVDRV R P51 are largely responsible for its high-level resistance to DRV. Here, we attempted to elucidate the role of each of the four amino acid substitutions in the development of DRV resistance...
March 6, 2018: MBio
Ruchi Omar, Arpita Yadav
In this opinion article, the authors discuss a number of interesting, beneficial properties of naturally occurring and synthetic cationic antimicrobial peptides (AMPs) with the prospective aim of bringing these compounds into therapeutic use to avoid antibiotic resistance and utilize their numerous properties. The structural diversity and the conformational freedom of these compounds adversely affects their mechanistic elucidation. Our molecular level mechanistic exploration of these peptides has shown their ion carriage properties and systematically explains their antibiotic activity through disruption of bacterial cell homeostasis and inhibition of 14-α demethylase enzyme...
2018: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
Phan Vuong Khac Thai, Dang Thi Minh Ha, Nguyen Thi Hanh, Jeremy Day, Sarah Dunstan, Nguyen Thi Quynh Nhu, Vo Sy Kiet, Nguyen Huu Lan, Nguyen Huy Dung, Nguyen Thi Ngoc Lan, Nguyen Thuong Thuong, Nguyen Ngoc Lan, Phạm Thị Thúy Liễu, Nguyễn Thị Hồng, Đào Công Điệp, Nguyễn Thị Kim Thanh, Nguyễn Văn Hội, Nguyễn Văn Nghĩa, Trương Ngọc Đại, Hoàng Quang Minh, Nguyễn Văn Thơm, Jeremy Farrar, Maxine Caws
BACKGROUND: Drug resistant tuberculosis (TB) is increasing in prevalence worldwide. Treatment failure and relapse is known to be high for patients with isoniazid resistant TB treated with standard first line regimens. However, risk factors for unfavourable outcomes and the optimal treatment regimen for isoniazid resistant TB are unknown. This cohort study was conducted when Vietnam used the eight month first line treatment regimen and examined risk factors for failure/relapse among patients with isoniazid resistant TB...
March 6, 2018: BMC Infectious Diseases
Muthukumar Balasubramaniam, Jui Pandhare, Chandravanu Dash
HIV-1 has already claimed over 35 million human lives globally. No curative treatments are currently available, and the only treatment option for over 36 million people currently living with HIV/AIDS are antiretroviral drugs that disrupt the function of virus-encoded proteins. However, such virus-targeted therapeutic strategies are constrained by the ability of the virus to develop drug-resistance. Despite major advances in HIV/AIDS research over the years, substantial knowledge gaps exist in many aspects of HIV-1 replication, especially its interaction with the host...
March 3, 2018: Viruses
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