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A Ocampo, P Domingo, P Fernández, J Diz, J R Barberá, M A Sepúlveda, X Salgado, M Rodriguez, J Santos, M Yzusqui, M I Mayorga, J F Lorenzo, A Bahamonde, P Bachiller, E Martínez, N Rozas, C Torres, A Muñoz, A Casado, D Podzamczer
Objectives: To analyse lipid changes and tolerability in a cohort of HIV-infected patients who switched their antiretroviral regimens to rilpivirine/emtricitabine/tenofovir (RPV/FTC/TDF) in a real-world setting. Methods: PRO-STR is a 48 week prospective observational post-authorization study in 25 hospitals. Patients with a viral load <1000 copies/mL, receiving at least 12 months of combination ART (cART), with constant posology for at least the prior 3 months, were categorized according to previous treatment [NNRTI or ritonavir-boosted PI (PI/r)]...
May 16, 2018: Journal of Antimicrobial Chemotherapy
Genyan Liu, Wenjie Wang, Youlan Wan, Xiulian Ju, Shuangxi Gu
Diarylpyrimidines (DAPYs), acting as HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs), have been considered to be one of the most potent drug families in the fight against acquired immunodeficiency syndrome (AIDS). To better understand the structural requirements of HIV-1 NNRTIs, three-dimensional quantitative structure⁻activity relationship (3D-QSAR), pharmacophore, and molecular docking studies were performed on 52 DAPY analogues that were synthesized in our previous studies. The internal and external validation parameters indicated that the generated 3D-QSAR models, including comparative molecular field analysis (CoMFA, q 2 = 0...
May 11, 2018: International Journal of Molecular Sciences
Obiageli Offor, Netanya Utay, David Reynoso, Anoma Somasunderam, Judith Currier, Jordan Lake
BACKGROUND: People with HIV are at for metabolic syndrome (MetS) and fatty liver disease, but the role of Antiretroviral therapy (ART) is poorly understood. MetS and fatty liver disease been associated with changes in adiponectin, soluble ST2 (sST2), chitinase 3-like 1 (Chi3L1), hyaluronic acid (HA), tissue inhibitor of metalloproteinase-1 (TIMP-1), lysyl oxidase-like-2 (LOXL2) and transforming growth factor β (TGF-β) concentrations in HIV-uninfected populations. Protease (PI) and non-nucleoside reverse transcriptase inhibitors (NNRTI) may contribute to these comorbidities, but the effects of switching from PI- or NNRTI to raltegravir (RAL) on these biomarkers is unknown...
2018: PloS One
Marco Vitoria, Andrew Hill, Nathan Ford, Meg Doherty, Polly Clayden, Francois Venter, David Ripin, Charles Flexner, Paul Domanico
: There are currently approximately 16 million people taking NNRTI-based first-line treatment in low- and middle-income countries. Most of these patients are using the combination of tenofovir (TDF), lamivudine (3TC) and efavirenz (EFV). The integrase inhibitor dolutegravir (DTG) has shown an improved safety profile compared to EFV in randomised studies. DTG also has a high barrier to development of drug resistance. New co-formulated tablets with TDF/3TC/DTG are being introduced into LMICs, for a median price of $75 per person-year...
May 9, 2018: AIDS
Qicai Xuan, Shuwen Liang, Weihong Qin, Shuting Yang, A-Mei Zhang, Ting Zhao, Hui Su, Zhiqing Xia, Binghui Wang, Xueshan Xia
BACKGROUND: The overall success of Human immunodeficiency virus type 1 (HIV-1) antiretroviral therapy (ART) was heavily challenged upon the occurrence of drug resistance. Dehong Prefecture witnessed not only the first report of HIV-1 infection but also the experimental adoption of antiviral treatment in China. The transmission and epidemic of HIV-1 in Dehong is impacted by cross-border activities. The characteristics of HIV-1 drug resistance among therapy-naïve Burmese entering travelers in Yunnan and their speculated origin are still not clarified...
May 8, 2018: BMC Infectious Diseases
Mohammad A Rai, Sam Pannek, Carl J Fichtenbaum
There are 36.7 million people living with HIV with 20.9 million having access to antiretroviral therapy (ART). Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) remain the 'backbone' of ART. However, the currently available nine NRTIs and five non-nucleoside reverse transcriptase inhibitors (NNRTIs) have significant side effects and resistance profiles. Areas covered: We summarize the mechanisms of resistance and other limitations of the existing NRTIs/NNRTIs. GS-9131, MK-8591, Elsulfavirine and Doravirine are four new agents that are furthest along in development...
May 8, 2018: Expert Opinion on Emerging Drugs
Thabo Diphoko, Simani Gaseitsiwe, Ishmael Kasvosve, Sikhulile Moyo, Harriet Okatch, Rosemary Musonda, Mark A Wainberg, Joseph Makhema, Richard Marlink, Vladimir Novitsky, M Essex
BACKGROUND: Rilpivirine (RPV) and Etravirine (ETR) are approved second-generation non-nucleoside reverse transcriptase inhibitors (NNRTI) for HIV treatment. There is a cross-resistance HIV mutation profile between first- and second-generation NNRTI drugs. We determined the prevalence of HIV-1drug-resistance mutations (DRM) to RPV and ETR in Botswana. METHODS: A total of 168 HIV-1 polymerase gene sequences from participants failing nevirapine or efavirenz-containing regimens were analysed for drug resistance mutations using the Stanford University HIV drug resistance database...
May 6, 2018: AIDS Research and Human Retroviruses
Lisa L Ross, Denise Shortino, Mark S Shaefer
<b>Background:</b> Pre-existing HIV drug resistance can jeopardize first-line antiretroviral therapy (ART) success. Changes in the prevalence of drug-resistance-associated mutations (DRMs) were analyzed from HIV-infected, ART-naïve, United States (USA) individuals seeking ART treatment from 2000-2009. <b>Methods: </b> HIV DRM data from 3,829 ART-naïve subjects were analyzed by year of sample collection using International Antiviral Society (IAS-USA) and World Health Organization (WHO) "surveillance" DRM definitions; minor IAS-USA-defined DRMs were excluded...
May 5, 2018: AIDS Research and Human Retroviruses
David R Bakal, Lara E Coelho, Paula M Luz, Jesse L Clark, Raquel B De Boni, Sandra W Cardoso, Valdilea G Veloso, Jordan E Lake, Beatriz Grinsztejn
Background: Obesity rates are increasing among HIV-infected individuals, but risk factors for obesity development on ART remain unclear. Objectives: In a cohort of HIV-infected adults in Rio de Janeiro, Brazil, we aimed to determine obesity rates before and after ART initiation and to analyse risk factors for obesity on ART. Methods: We retrospectively analysed data from individuals initiating ART between 2000 and 2015. BMI was calculated at baseline (time of ART initiation)...
May 2, 2018: Journal of Antimicrobial Chemotherapy
Xiaoyu Liu, Panpan Chen, Xiaoyu Li, Mingyu Ba, Xiaozhen Jiao, Ying Guo, Ping Xie
SG-1 was previously identified as a potent Non-nucleoside reverse transcriptase inhibitors (NNRTI) which works through inhibition of reverse transcriptase (RT) RNA-dependent DNA polymerase activity via a direct binding event. To further investigate the relationship between its structure and activity, four series of novel analogues were designed and synthesized with 12 of them inhibiting HIV-1 replication with IC50 s in the range 0.09-6.71 μM. Compound 4b, 4c, 4f, 2 and 6b were further tested on two NNRTI-resistant HIV-1 strains and one NNRTI-resistant superbug...
April 20, 2018: Bioorganic & Medicinal Chemistry Letters
Roy M Gulick
Over the past 30 years, antiretroviral drug regimens for treating HIV infection have become more effective, safer, and more convenient. Despite 31 currently approved drugs, the pipeline of investigational HIV drugs remains full. Investigational antiretroviral drugs include the nucleoside analogue reverse transcriptase translocation inhibitor (NRTTI) MK-8591, a long-acting compound that could be dosed once weekly. Investigational nonnucleoside analogue reverse transcriptase inhibitors (NNRTIs) include doravirine, which is active in vitro against NNRTI-resistant HIV and was potent and well-tolerated when used in combination with a dual-nucleoside analogue RTI (nRTI) backbone in treatment-naive individuals...
April 2018: Topics in Antiviral Medicine
Leondios G Kostrikis, Johana Hezka, Dora C Stylianou, Evangelia Kostaki, Maria Andreou, Ioanna Kousiappa, Dimitrios Paraskevis, Ioannis Demetriades
A molecular epidemiology study of HIV-1 infection was conducted in one hundred diagnosed and untreated HIV-1-infected patients in Cyprus between 2010 and 2012, representing 65.4% of all the reported HIV-1 infections in Cyprus in this three-year period, using a previously defined enrolment strategy. Eighty-two patients were newly diagnosed (genotypic drug resistance testing within six months from diagnosis), and eighteen patients were HIV-1 diagnosed for a longer period or the diagnosis date was unknown. Phylogenetic trees of the pol sequences obtained in this study with reference sequences indicated that subtypes B and A1 were the most common subtypes present and accounted for 41...
2018: PloS One
Rose Masaba, Craig B Borkowf, Sonali Girde, Clement Zeh, Richard Ndivo, Isabella Nyang'au, Kevin Achola, Timothy K Thomas, Shirley Lee Lecher
BACKGROUND: For HIV-infected pregnant and breastfeeding women, antiretroviral therapy (ART) is known to reduce the mother's risk of passing the infection to her child. However, concerns remain about possible associations between various components of different ART regimens and adverse fetal and infant outcomes. As part of a clinical trial in western Kenya for the prevention of mother-to-child transmission (PMTCT) of HIV, pregnant women received one of two different ART regimens. METHODS: The original PMTCT study conducted in Kenya enrolled 522 HIV-infected, ART-naïve pregnant women...
April 19, 2018: AIDS
Esther Rodríguez-Gallego, Josep Gómez, Pere Domingo, Sara Ferrando-Martínez, Joaquim Peraire, Consuelo Viladés, Sergi Veloso, Miguel López-Dupla, Raúl Beltrán-Debón, Verónica Alba, Montserrat Vargas, Alfonso J Castellano, Manuel Leal, Yolanda María Pacheco, Ezequiel Ruiz-Mateos, Félix Gutiérrez, Francesc Vidal, Anna Rull
BACKGROUND AND AIMS: Dyslipidemia in HIV-infected patients is unique and pathophysiologically associated with host factors, HIV itself and the use of antiretroviral therapy (ART). The use of nuclear magnetic resonance spectroscopy (NMR) provides additional data to conventional lipid measurements concerning the number of lipoprotein subclasses and particle sizes. METHODS: To investigate the ability of lipoprotein profile, we used a circulating metabolomic approach in a cohort of 103 ART-naive HIV-infected patients, who were initiating non-nucleoside analogue transcriptase inhibitor (NNRTI)-based ART, and we subsequently followed up these patients for 36 months...
April 9, 2018: Atherosclerosis
Zhipeng Huo, Heng Zhang, Dongwei Kang, Zhongxia Zhou, Gaochan Wu, Samuel Desta, Xiaofang Zuo, Zhao Wang, Lanlan Jing, Xiao Ding, Dirk Daelemans, Erik De Clercq, Christophe Pannecouque, Peng Zhan, Xinyong Liu
A novel series of diarylpyrimidine derivatives, which could simultaneously occupy the classical NNRTIs binding pocket (NNIBP) and the newly reported "NNRTI Adjacent" binding site, were designed, synthesized, and evaluated for their antiviral activities in MT-4 cell cultures. The results demonstrated that six compounds ( 20 , 27 and 31 - 34 ) showed excellent activities against wild-type (WT) HIV-1 strain (EC50 = 2.4-3.8 nM), which were more potent than that of ETV (EC50 = 4.0 nM). Furthermore, 20 , 27 , 33 , and 34 showed more potent or equipotent activity against single mutant HIV-1 strains compared to that of ETV...
April 12, 2018: ACS Medicinal Chemistry Letters
Leila Sadeghi, Mahin Lolaie, Reza Adl Tabatabai, Saeed Bayanolhagh, Leila Taj, Niloofar Eghbal Ahmadi, Negin Abedinzadeh, Farzaneh Vakili, Ghazaleh Ahmadi, Minoo Mohraz
BACKGROUND: Determination of drug resistant mutations has a crucial role in the management of HIV-1 infected patients. OBJECTIVE: The aim of the current study was to evaluate drug resistance profile of RT and PR gene, and find the correlation between drug resistance mutation and ART regimen to intensify physicians ' options for the most effective therapy and help to establish health related policies at the national level in Iran. METHOD: HIV-1 RNA of 34 samples was extracted from plasma and RT Nested- PCR was performed and the final products were sequenced...
April 15, 2018: Infectious Disorders Drug Targets
Pablo Lopez, Omayra De Jesus, Yasuhiro Yamamura, Nayra Rodriguez, Andrea Arias, Raphael Sanchez, Yadira Rodriguez, Vivian Tamayo-Agrait, Wilfredo Cuevas, Vanessa Rivera-Amill
Human immunodeficiency virus-1 (HIV-1) subtype B virus is the most prevalent subtype in Puerto Rico (PR), accounting for about 90% of infection in the island. Recently, other subtypes and circulating recombinant forms (CRF) including F (12_BF), A (01_BF), and CRF-39 BF-like have been identified. The purpose of this study is to assess the distribution of drug resistance mutations and subtypes in PR. A total of 846 nucleotide sequences from the period comprising 2013 through 2017 were obtained from our "HIV Genotyping" test file...
April 15, 2018: AIDS Research and Human Retroviruses
Sébastien Pasquereau, Amit Kumar, Wasim Abbas, Georges Herbein
Akt signaling plays a central role in many biological processes that are key players in human immunodeficiency virus 1 (HIV-1) pathogenesis. The persistence of latent reservoirs in successfully treated patients, mainly located in macrophages and latently infected resting CD4+ T cells, remains a major obstacle in HIV-1 eradication. We assessed the in vitro effects of an HIV protease inhibitor (PI) and a non-nucleoside reverse transcriptase inhibitor (NNRTI) on HIV-1 Nef-induced Akt activation in macrophages and on HIV-1 reactivation in U1 monocytoid cells...
April 13, 2018: Viruses
R F Kamil, U Debnath, S Verma, Y S Prabhakar
The Acquired Immunodeficiency Syndrome is an immunesuppressant disorder caused by human immunodeficiency virus, the upshot of which can be observed on affected individual's immune system. The salient role of HIV-1RT in progression & development of disease makes it a significant target. In current the study a 3D-model of HIV-1 RT enzyme having following multiple mutations K103N, Y181C and Y188L was developed through homology modeling with the aim to perceive effects of multiple mutations on binding pocket and binding interractions...
April 12, 2018: Current HIV Research
S Nuvoli, G Caruana, S Babudieri, P Solinas, G Pellicanò, B Piras, V Fiore, P Bagella, G M Calia, M Yue, A Spanu, G Madeddu
OBJECTIVE: We aimed to quantitatively evaluate body fat composition in a group of HIV patients treated with Highly Active Anti-retroviral Therapy (HAART) to ascertain both fat loss and fat distribution changes and to identify possible therapeutic and host related associated risk factors. PATIENTS AND METHODS: A total of 180 patients with available total body DEXA scan were assigned to a) Group 1, with clinically evident body fat changes, (BFC) and b) Group 2, without BFC...
March 2018: European Review for Medical and Pharmacological Sciences
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