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NNRTI HIV

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https://www.readbyqxmd.com/read/29156381/structure-based-methods-to-predict-mutational-resistance-to-diarylpyrimidine-non-nucleoside-reverse-transcriptase-inhibitors
#1
Syeda Maryam Azeem, Alecia N Muwonge, Nehaben Thakkar, Kristina W Lam, Kathleen M Frey
Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) is a leading cause of HIV treatment failure. Often included in antiviral therapy, NNRTIs are chemically diverse compounds that bind an allosteric pocket of enzyme target reverse transcriptase (RT). Several new NNRTIs incorporate flexibility in order to compensate for lost interactions with amino acid conferring mutations in RT. Unfortunately, even successful inhibitors such as diarylpyrimidine (DAPY) inhibitor rilpivirine are affected by mutations in RT that confer resistance...
November 9, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29152052/discovery-of-thiophene-3-2-d-pyrimidine-derivatives-as-potent-hiv-1-nnrtis-targeting-the-tolerant-region-i-of-nnibp
#2
Dongwei Kang, Xiao Ding, Gaochan Wu, Zhipeng Huo, Zhongxia Zhou, Tong Zhao, Da Feng, Zhao Wang, Ye Tian, Dirk Daelemans, Erik De Clercq, Christophe Pannecouque, Peng Zhan, Xinyong Liu
Our previous studies led us to conclude that thiophene[3,2-d]pyrimidine is a promising scaffold for diarylpyrimidine (DAPY)-type anti-HIV agents with potent activity against resistance-associated human immunodeficiency virus (HIV) variants (J. Med. Chem. 2016, 59, 7991-8007; J. Med. Chem. 2017, 60, 4424-4443). In the present study, we designed and synthesized a series of thiophenepyrimidine derivatives with various substituents in the right wing region of the structure with the aim of developing new interactions with the tolerant region I of the binding pocket of the HIV-1 non-nucleoside reverse transcriptase (NNRTI), and we evaluated their activity against a panel of mutant HIV-1 strains...
November 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29137167/transmission-dynamics-of-hiv-1-drug-resistance-among-treatment-na%C3%A3-ve-individuals-in-greece-the-added-value-of-molecular-epidemiology-to-public-health
#3
Dimitrios Paraskevis, Evangelia Kostaki, Panagiotis Gargalianos, Georgios Xylomenos, Marios Lazanas, Maria Chini, Athanasios Skoutelis, Vasileios Papastamopoulos, Dimitra Paraskeva, Anastasia Antoniadou, Antonios Papadopoulos, Mina Psichogiou, Georgios L Daikos, Georgios Chrysos, Vasileios Paparizos, Sofia Kourkounti, Helen Sambatakou, Nikolaos V Sipsas, Malvina Lada, Periklis Panagopoulos, Efstratios Maltezos, Stylianos Drimis, Angelos Hatzakis
The presence of human immunodeficiency virus type 1 (HIV-1) drug resistance among drug-naïve patients remains stable, although the proportion of patients with virological failure to therapy is decreasing. The dynamics of transmitted resistance among drug-naïve patients remains largely unknown. The prevalence of non-nucleoside reverse transcriptase inhibitors (NNRTI) resistance was 16.9% among treatment-naïve individuals in Greece. We aimed to investigate the transmission dynamics and the effective reproductive number (Re) of the locally transmitted NNRTI resistance...
November 13, 2017: Genes
https://www.readbyqxmd.com/read/29136743/-drug-resistance-mutations-and-its-associated-factors-among-579-hiv-aids-patients-experiencing-failure-of-antiretroviral-therapy-in-jiangsu-province-china
#4
P P Xiao, J Lu, H Y Hu, X Q Xu, P Ding, G F Fu, X P Huan, Y Zhou, H T Yang
Objective: To understand the incidence and related factors of HIV-1 drug resistance among HIV/AIDS patients experiencing treatment failure in Jiangsu province, China. Methods: The HIV/AIDS integrated prevention and control data information management system of China were used to collect the basic data of patients, blood specimens were collected from patients who had antiretroviral therapy (ART) failure with ≥12 months and older than 18 years in 2016 in Jiangsu, excluding cases with missing information, 713 cases were enrolled in this study...
November 6, 2017: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
https://www.readbyqxmd.com/read/29136032/virological-response-and-resistance-among-hiv-infected-children-receiving-long-term-antiretroviral-therapy-without-virological-monitoring-in-uganda-and-zimbabwe-observational-analyses-within-the-randomised-arrow-trial
#5
Alexander J Szubert, Andrew J Prendergast, Moira J Spyer, Victor Musiime, Philippa Musoke, Mutsa Bwakura-Dangarembizi, Patricia Nahirya-Ntege, Margaret J Thomason, Emmanuel Ndashimye, Immaculate Nkanya, Oscar Senfuma, Boniface Mudenge, Nigel Klein, Diana M Gibb, A Sarah Walker
BACKGROUND: Although WHO recommends viral load (VL) monitoring for those on antiretroviral therapy (ART), availability in low-income countries remains limited. We investigated long-term VL and resistance in HIV-infected children managed without real-time VL monitoring. METHODS AND FINDINGS: In the ARROW factorial trial, 1,206 children initiating ART in Uganda and Zimbabwe between 15 March 2007 and 18 November 2008, aged a median 6 years old, with median CD4% of 12%, were randomised to monitoring with or without 12-weekly CD4 counts and to receive 2 nucleoside reverse transcriptase inhibitors (2NRTI, mainly abacavir+lamivudine) with a non-nucleoside reverse transcriptase inhibitor (NNRTI) or 3 NRTIs as long-term ART...
November 2017: PLoS Medicine
https://www.readbyqxmd.com/read/29135577/protease-inhibitors-and-preterm-delivery-another-piece-in-the-puzzle
#6
Graziella Favarato, Claire L Townsend, Heather Bailey, Helen Peters, Pat Tookey, Graham P Taylor, Claire Thorne
BACKGROUND: Questions remain regarding preterm delivery (PTD) risk in HIV-infected women on antiretroviral therapy (ART), including the role of ritonavir-boosted protease inhibitors (PI/r), timing of ART initiation and immune status. METHODS: We examined data from the UK/Ireland National Study of HIV in Pregnancy and Childhood on women with HIV delivering a singleton live infant in 2007-2015, including those pregnancies receiving PI/r-based (n=4184) or non-nucleoside reverse transcriptase inhibitors (NNRTI)-based regimens (n = 1889)...
November 10, 2017: AIDS
https://www.readbyqxmd.com/read/29128646/hiv-drug-resistance-following-a-decade-of-free-antiretroviral-therapy-program-in-india-a-review
#7
REVIEW
Santosh Karade, Devidas N Chaturbhuj, Sourav Sen, Rajneesh K Joshi, Smita S Kulkarni, Subramanian Shankar, Raman R Gangakhedkar
OBJECTIVE: The objective of this review is to assess the burden of HIV drug resistance mutations (DRM) in Indian adults exposed to first-line ART as per national guidelines. METHODS: We performed advanced search for the published literature on HIV drug resistance in India in PubMed and Scopus. From each publication data pertaining to age, sex, CD4 count and viral load, prevalence of NRTI/NNRTI drug resistance mutations (DRM) was extracted. Year-wise Indian HIV-1 reverse transcriptase (RT) sequences were retrieved from Los Alamos HIV database and mutation analyses were performed...
November 8, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/29111294/oxygen-binding-isotope-effects-of-triazole-based-hiv-1-reverse-transcriptase-inhibitors-indicate-the-actual-binding-site
#8
Agnieszka Krzemińska, Tomasz Frączek, P Paneth
Binding isotope effects (BIEs) associated with binding of four triazole-based ligands to HIV-1 reverse transcriptase have been calculated at the QM/MM MD level of theory. Two main binding sites: allosteric cavity and RNase H active site, as well as three other sites reported in the literature (the Knuckles, the NNRTI Adjacent, and Incoming Nucleotide Binding) have been considered. The interactions between inhibitors and these protein sites have been quantified by binding free energies obtained from free energy perturbation (FEP) calculations, supported by interaction energy analysis...
December 1, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29105160/strength-in-amalgamation-newer-combination-agents-for-hiv-and-implications-for-practice
#9
Christopher McCoy, Melissa Badowski, Elizabeth Sherman, Rustin Crutchley, Ethan Smith, Daniel B Chastain
Antiretroviral (ART) therapy for treatment of human immunodeficiency virus (HIV) infection has undergone significant changes over the past 30 years. Many single tablet regimens (STR), including newer fixed dose combination (FDC) tablets, are available, offering patients several options for choosing a treatment regimen that works best for them. Given these changes, patients are more likely to adhere to treatment, achieve better clinical outcomes, and experience both fewer side effects and drug-drug interactions...
November 3, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/29103079/effectiveness-of-kidney-transplantation-in-hiv-infected-recipients-under-combination-antiretroviral-therapy-a-single-cohort-experience-brescia-northern-italy
#10
Ilaria Izzo, Salvatore Casari, Nicola Bossini, Maria Antonia Forleo, Silvio Sandrini, Emanuele Focà, Nigritella Brianese, Giulia Zambolin, Claudia Chirico, Giovanni Cancarini, Francesco Castelli
PURPOSE: Kidney transplantation was recently introduced for the treatment of end stage renal disease (ESRD) in HIV-infected patients. We report the results of the first 28 procedures at our centre. METHODS: A retrospective study was conducted on HIV-infected patients evaluated for kidney transplantation between January 2005 and October 2016. Patients were selected and monitored by the kidney transplantation and infectious diseases teams, according to the national protocol...
November 4, 2017: Infection
https://www.readbyqxmd.com/read/29081666/high-rate-of-hiv-1-drug-resistance-in-treatment-failure-patients-in-taiwan-2009-2014
#11
Hung-Chin Tsai, I-Tzu Chen, Kuan-Sheng Wu, Yu-Ting Tseng, Cheng-Len Sy, Jui-Kuang Chen, Susan Shin-Jung Lee, Yao-Shen Chen
BACKGROUND: Drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs) has been associated with loss of viral suppression measured by a rise in HIV-1 RNA levels, a decline in CD4 cell counts, persistence on a failing treatment regimen, and lack of adherence to combination antiretroviral therapy. OBJECTIVES: This study aimed to monitor the prevalence and risk factors associated with drug resistance in Taiwan after failure of first-line therapy...
2017: Infection and Drug Resistance
https://www.readbyqxmd.com/read/29068286/dynamic-hiv-1-genetic-recombination-and-genotypic-drug-resistance-among-treatment-experienced-adults-in-northern-ghana
#12
Nicholas Israel Nii-Trebi, James Ashun Mensah Brandful, Shiro Ibe, Wataru Sugiura, Jacob Samson Barnor, Patrick Owiredu Bampoh, Shoji Yamaoka, Tetsuro Matano, Kazuhisa Yoshimura, Koichi Ishikawa, William Kwabena Ampofo
PURPOSE: There have been hardly any reports on the human immunodeficiency virus type 1 (HIV-1) drug-resistance profile from northern Ghana since antiretroviral therapy (ART) was introduced over a decade ago. This study investigated prevailing HIV-1 subtypes and examined the occurrence of drug resistance in ART-experienced patients in Tamale, the capital of the Northern Region of Ghana. METHODOLOGY: A cross-sectional study was carried out on HIV-infected adult patients receiving first-line ART...
October 25, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/29066858/rilpivirine-the-key-for-long-term-success
#13
Pompeyo Viciana
During the past 30 years of antiretroviral therapy, continuous improvements in drug discovery have provided increasingly potent and safer antivirals that have transformed HIV infection in a chronic illness, rarely fatal. Non-nucleoside reverse-transcriptase inhibitors (NNRTIs) are frequently used as part of any antiretroviral combination therapy. Side effects and low resistance barrier of fi rst-generation NNRTIs (e.g., nevirapine and efavirenz) have been overcome with rilpivirine (RPV), and the last NNRTI approved for the treatment of HIV infection...
October 2017: AIDS Reviews
https://www.readbyqxmd.com/read/29052340/absence-of-neurocognitive-disadvantage-associated-with-paediatric-hiv-subtype-a-infection-in-children-on-antiretroviral-therapy
#14
Paul Bangirana, Theodore D Ruel, Michael J Boivin, Satish K Pillai, Leila B Giron, Alla Sikorskii, Asish Banik, Jane Achan
INTRODUCTION: Infection with HIV subtype A has been associated with poorer neurocognitive outcomes compared to HIV subtype D in Ugandan children not eligible for antiretroviral therapy (ART). In this study, we sought to determine whether subtype-specific differences are also observed among children receiving ART. MATERIALS AND METHODS: Children were recruited from a clinical trial in which they were randomized to receive either lopinavir (LPV)- or non-nucleoside reverse transcriptase inhibitor (NNRTI)- based ART (NCT00978068)...
October 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/29049402/upward-trends-of-acquired-drug-resistances-in-ethiopian-hiv-1c-isolates-a-decade-longitudinal-study
#15
Andargachew Mulu, Melanie Maier, Uwe Gerd Liebert
BACKGROUND: The emergence, accumulation and spread of HIV-1 drug resistance strains in Africa could compromise the effectiveness of HIV treatment programs. This study was aimed at determining the incidence of virological failure and acquired drug resistance mutations overtime and identifying the most common mutational pathways of resistance in a well characterized HIV-1C infected Ethiopian cohort. METHODS: A total of 320 patients (220 ART naïve and 100 on first lines ART) were included and followed...
2017: PloS One
https://www.readbyqxmd.com/read/29029095/identification-of-novel-bifunctional-hiv-1-reverse-transcriptase-inhibitors
#16
Ming-Tain Lai, Paul Tawa, Anick Auger, Deping Wang, Hua-Poo Su, Youwei Yan, Daria J Hazuda, Michael D Miller, Ernest Asante-Appiah, Roman A Melnyk
Objectives: The increasing prevalence of mutations in HIV-1 reverse transcriptase (RT) that confer resistance to existing NRTIs and NNRTIs underscores the need to develop RT inhibitors with novel mode-of-inhibition and distinct resistance profiles. Methods: Biochemical assays were employed to identify inhibitors of RT activity and characterize their mode of inhibition. The antiviral activity of the inhibitors was assessed by cell-based assays using laboratory HIV-1 isolates and MT4 cells...
September 26, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29021409/hiv-1-viral-load-and-resistance-in-genital-secretions-in-patients-taking-protease-inhibitor-based-second-line-therapy-in-africa
#17
Anne Hoppe, Marina Giuliano, Abbas Lugemwa, Jennifer A Thompson, Marco Floridia, Ann S Walker, Ismail Senoga, Mary C Abwola, Maria F Pirillo, Cissy M Kityo, Alejandro Arenas-Pinto, Nicholas I Paton
BACKGROUND: HIV is transmitted primarily through sexual intercourse, and the objective of this study was therefore to assess whether there is occult viral replication and resistance in genital secretions in patients on protease inhibitor (PI)-based second-line therapy. METHODS: HIV-infected adults taking ritonavir-boosted lopinavir with either two NRTIs, raltegravir, or as monotherapy for 96 weeks were enrolled at seven clinical sites in Uganda. Viral load (VL) was measured in cervico-vaginal secretions or semen and in a corresponding plasma sample...
October 11, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/29020335/hiv-drug-resistance-in-african-infants-and-young-children-newly-diagnosed-with-hiv-a-multicounty-analysis
#18
Michael R Jordan, Martina Penazzato, Amandine Cournil, Adolfo Vubil, Ilesh Jani, Gillian Hunt, Sergio Carmona, Gugu Maphalala, Nobuhle Mthethwa, Christine Watera, Pontiano Kaleebu, Christine Chakanyuka Musanhu, Sekesai Mtapuri-Zinyowera, Janet Dzangare, Martine Peeters, Chunfu Yang, Neil Parkin, Silvia Bertagnolio
Background: Prevention of mother-to-child transmission (PMTCT) of HIV programs have been scaled-up in many low- and middle-income countries; however, HIV drug resistance (HIVDR) data amongst HIV-1-infected young children remain limited. Methods: Surveys of pre-treatment HIVDR amongst children younger than 18 months of age who were diagnosed with HIV through Early Infant Diagnosis were conducted in five sub-Saharan African countries (Mozambique, Swaziland, South Africa, Uganda, and Zimbabwe) between 2011 and 2014 following World Health Organization guidance...
August 8, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28991889/trends-in-drug-resistance-prevalence-hiv-1-variants-and-clinical-status-in-hiv-1-infected-pediatric-population-in-madrid-1993-2015-analysis
#19
Patricia Rojas Sánchez, Sara Domínguez, Santiago Jiménez De Ory, Luis Prieto, Pablo Rojo, Pepa Mellado, Marisa Navarro, Rafael Delgado, José Tomas Ramos, África Holguín
BACKGROUND: The expanded use of long-term antiretroviral treatments in infected children may exacerbate the problem of drug resistance mutations (HIVDR) selection, which can compromise treatment efficiency. OBJECTIVE: We describe the temporal trends of HIVDR and the HIV-1 variants during 23 years (1993-March 2016) in the Madrid cohort of HIV-infected children and adolescents. METHODS: We selected patients with at least one available HIV-1 pol sequence/genotypic resistance profile, establishing different groups according to the sampling year of first resistance data...
October 6, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28986714/comparison-of-antiretroviral-drug-resistance-among-treatment-naive-and-treated-hiv-infected-individuals-in-shiraz-iran
#20
Mohammad Ali Davarpanah, Nasrin Motazedian, Hassan Joulaei, Mohammad Reza Aghasadeghi, Hossein Faramarzi, Ehsan Aghah
The use of anti-retroviral therapy has been effective in controlling the spread of HIV-1, and has prolonged life expectancy, but this success can be affected by the emergence of drug resistance. The main goal of this study was to investigate drug resistance in the reverse transcriptase (RT), and protease (PR) genes among HIV-1 infected individuals. We systematically selected 59 HIV-1 infected individuals from Shiraz Voluntary Counseling and Testing Center (29 treatment- naïve and 30 treated). In this study intravenous drug users older than 18 were included in this study...
October 6, 2017: Archives of Virology
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