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NNRTI HIV

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https://www.readbyqxmd.com/read/28198788/high-rates-of-baseline-drug-resistance-and-virologic-failure-among-art-na%C3%A3-ve-hiv-infected-children-in-mali
#1
Claudia S Crowell, Almoustapha I Maiga, Mariam Sylla, Babafemi Taiwo, Niaboula Kone, Assaf P Oron, Robert L Murphy, Anne-Geneviève Marcelin, Ban Traore, Djeneba B Fofana, Gilles Peytavin, Ellen G Chadwick
BACKGROUND: Limited data exist on drug resistance and antiretroviral treatment (ART) outcomes in HIV-1 infected children in West Africa. We determined the prevalence of baseline resistance and correlates of virologic failure (VF) in a cohort of ART naïve HIV-1 infected children <10 years of age initiating ART in Mali. METHODS: Reverse transcriptase and protease genes were sequenced at baseline (before ART) and at 6 months. Resistance was defined according to the Stanford HIV Genotypic Resistance database...
February 13, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28187212/an-analysis-of-drug-resistance-among-people-living-with-hiv-aids-in-shanghai-china
#2
Fengdi Zhang, Li Liu, Meiyan Sun, Jianjun Sun, Hongzhou Lu
BACKGROUND: Understanding the mechanisms of drug resistance can facilitate better management of antiretroviral therapy, helping to prevent transmission and decrease the morbidity and mortality of people living with HIV/AIDS. However, there is little data about transmitted drug resistance and acquired drug resistance for HIV/AIDS patients in Shanghai. METHODS: A retrospective cohort study of HIV-infected patients who visited the Department of Infectious Disease from June 2008 to June 2015 was conducted in Shanghai, China...
2017: PloS One
https://www.readbyqxmd.com/read/28182989/6-cyclohexylmethyl-3-hydroxypyrimidine-2-4-dione-as-an-inhibitor-scaffold-of-hiv-reverase-transcriptase-impacts-of-the-3-oh-on-inhibiting-rnase-h-and-polymerase
#3
Jing Tang, Karen A Kirby, Andrew D Huber, Mary C Casey, Juan Ji, Daniel J Wilson, Stefan G Sarafianos, Zhengqiang Wang
3-Hydroxypyrimidine-2,4-dione (HPD) represents a versatile chemical core in the design of inhibitors of human immunodeficiency virus (HIV) reverse transcriptase (RT)-associated RNase H and integrase strand transfer (INST). We report herein the design, synthesis and biological evaluation of an HPD subtype (4) featuring a cyclohexylmethyl group at the C-6 position. Antiviral testing showed that most analogues of 4 inhibited HIV-1 in the low nanomolar to submicromolar range, without cytotoxicity at concentrations up to 100 μM...
January 30, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28178281/surveillance-of-hiv-1-pol-transmitted-drug-resistance-in-acutely-and-recently-infected-antiretroviral-drug-na%C3%A3-ve-persons-in-rural-western-kenya
#4
Harris Onywera, David Maman, Seth Inzaule, Erick Auma, Kennedy Were, Harrison Fredrick, Prestone Owiti, Valarie Opollo, Jean-François Etard, Irene Mukui, Andrea A Kim, Clement Zeh
HIV-1 transmitted drug resistance (TDR) is of increasing public health concern in sub-Saharan Africa with the rollout of antiretroviral (ARV) therapy. Such data are, however, limited in Kenya, where HIV-1 drug resistance testing is not routinely performed. From a population-based household survey conducted between September and November 2012 in rural western Kenya, we retrospectively assessed HIV-1 TDR baseline rates, its determinants, and genetic diversity among drug-naïve persons aged 15-59 years with acute HIV-1 infections (AHI) and recent HIV-1 infections (RHI) as determined by nucleic acid amplification test and both Limiting Antigen and BioRad avidity immunoassays, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28171682/unusual-electrospray-ionization-induced-fragmentation-structural-elucidation-of-an-in-process-synthetic-intermediate-of-doravirine-mk-1439-using-lc-hrms-ms-and-2d-nmr
#5
Huaming Sheng, Katrina W Lexa, Li-Kang Zhang, Rong-Sheng Yang, Timothy J Wright, Benjamin D Sherry, Roy Helmy, Gary E Martin
RATIONALE: During the development of a novel synthetic route to doravirine; (1), a human immunodeficiency type 1 virus (HIV-1) nonnucleoside reverse transcriptase inhibitor (NNRTI), an unanticipated reaction intermediate, methyl (Z)-2-(3-chloro-5-cyanophenoxy)-5-(3-(3-chloro-5-cyanophenoxy)-2-oxo-4-(trifluoromethyl)pyridin-1(2H)-yl)-5-ethoxy-3-(trifluoromethyl)pent-2-enoate (2), was isolated. Moreover, the unusual ESI induced fragmentation was observed for 2. Hence, efforts were made towards the understanding of the structure of 2, which was crucial for the understanding of the reaction mechanism...
February 7, 2017: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/28167742/structural-and-preclinical-studies-of-computationally-designed-non-nucleoside-reverse-transcriptase-inhibitors-for-treating-hiv-infection
#6
Shalley N Kudalkar, Jagadish Beloor, Albert H Chan, Won-Gil Lee, William L Jorgensen, Priti Kumar, Karen S Anderson
The clinical benefits of human immunodeficiency virus type 1 (HIV-1) non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs) are hindered by their unsatisfactory pharmacokinetic (PK) properties along with the rapid development of drug-resistant variants. However, the clinical efficacy of these inhibitors can be improved by developing compounds with enhanced pharmacological profiles and heightened antiviral activity. We used computational and structure-guided design to develop two next-generation NNRTI drug candidates, compounds I and II, which are members of a class of catechol diethers...
February 6, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28129253/hiv-drug-resistance-mutations-in-non-b-subtypes-after-prolonged-virological-failure-on-nnrti-based-first-line-regimens-in-sub-saharan-africa
#7
Cissy Kityo, Jennifer Thompson, Immaculate Nankya, Anne Hoppe, Emmanuel Ndashimye, Colin Warambwa, Ivan Mambule, Joep J van Oosterhout, Kara Wools-Kaloustian, Silvia Bertagnolio, Philippa J Easterbrook, Peter Mugyenyi, A Sarah Walker, Nicholas Paton
OBJECTIVE: To determine drug resistance mutation (DRM) patterns in a large cohort of patients failing non-nucleoside-reverse-transcriptase-inhibitor (NNRTI)-based first-line antiretroviral therapy (ART) regimens in programmes without routine viral load (VL) monitoring and to examine inter-subtype differences in DRMs. DESIGN: Sequences from 787 adults/adolescents who failed an NNRTI-based first-line regimen in 13 clinics in Uganda, Kenya, Zimbabwe, Malawi were analysed...
January 25, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28124959/-prevalence-of-human-leukocyte-antigen-hla-b-57-01-in-hiv-infected-patients
#8
Aydın Deveci, Ahmet Yılmaz Çoban, Belma Durupınar
Deaths related with human immunodeficiency virus (HIV) infections have been decreased by the introduction of combined anti-retroviral therapy (ART) into the clinical practice. Combined ART usually consists of two nucleoside/nucleotide analogs reverse transcriptase inhibitors (NRTI) that is called backbone and a third drug that belongs to either non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI), integrase strand transfer inhibitors (INSTI) or entry inhibitors. During abacavir therapy which is a member of NRTI, hypersensitivity reactions can occur approximately 4-9% of the patients that lead difficulties for the management of HIV infections...
October 2016: Mikrobiyoloji Bülteni
https://www.readbyqxmd.com/read/28121670/effect-of-antiretroviral-therapy-on-malaria-incidence-in-hiv-infected-ugandan-adults
#9
Ronnie P Kasirye, Heiner Grosskurth, Paula Munderi, Jonathan Levin, Zacchaeus Anywaine, Andrew Nunn, Anatoli Kamali, Kathy Baisley
INTRODUCTION: Using the data of a trial on cotrimoxazole (CTX) cessation, we investigated the effect of different antiretroviral therapy (ART) regimens on the incidence of clinical malaria. METHODS: During the cotrimoxazole cessation trial (ISRCTN44723643), HIV-infected Ugandan adults with CD4 at least 250 cells/μl were randomized to receive either CTX prophylaxis or placebo and were followed for a median of 2.5 years. Blood slides for malaria microscopy were examined at scheduled visits and at unscheduled visits when the participant felt unwell...
February 20, 2017: AIDS
https://www.readbyqxmd.com/read/28114955/hiv-1-drug-resistant-mutations-and-related-risk-factors-among-hiv-1-positive-individuals-experiencing-treatment-failure-in-hebei-province-china
#10
Xinli Lu, Hongru Zhao, Yuqi Zhang, Wei Wang, Cuiying Zhao, Yan Li, Lin Ma, Ze Cui, Suliang Chen
BACKGROUND: To understand HIV-1 drug resistance in 11 prefectures of Hebei Province, China, we implemented a cross-sectional HIV-1 molecular epidemiological survey. METHODS: Blood samples were collected from 122 newly diagnosed drug-naïve HIV-1-positive individuals and 229 antiretroviral therapy (ART)-failure individuals from 11 prefectures in Hebei Province, China. Patient demographic data were obtained via face-to-face interviews using a standardized questionnaire when blood samples were collected...
January 23, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28110956/anti-hiv-diphyllin-glycosides-from-justicia-gendarussa
#11
Hong-Jie Zhang, Emily Rumschlag-Booms, Yi-Fu Guan, Kang-Lun Liu, Dong-Ying Wang, Wan-Fei Li, Van Hung Nguyen, Nguyen Manh Cuong, Djaja Doel Soejarto, Harry H S Fong, Lijun Rong
In a search for new anti-HIV active leads from over several thousands of plant extracts, we have identified a potent plant lead. The active plant is determined as Justicia gendarussa (Acanthaceae), a medicinal plant that has been used for the treatment of injury, arthritis and rheumatism in Asia including China. Our bioassay-guided fractionation of the methanol extract of the stems and barks of the plant led to the isolation of two anti-HIV compounds, justiprocumins A and B. The compounds are identified as new arylnaphthalide lignans (ANL) glycosides...
January 19, 2017: Phytochemistry
https://www.readbyqxmd.com/read/28107870/identifications-of-drug-resistance-mutations-among-antiretroviral-treatment-naive-hiv-1-patients-in-peninsular-malaysia
#12
Rozainanee Mohd Zain, Nabila Ibrahim, Suriani Ismail, Jeyanthi Suppiah, Nor Aziyah Mat Rahim, Ravindran Thayan
OBJECTIVE: To determine drug resistance mutations and the HIV-1 subtypes among antiretroviral treatment naive HIV-1 patients in Peninsular Malaysia. METHODS: A total of 45 samples from four hospitals that provide HIV viral load services were subjected to the amplification of the protease and two third of reverse transcriptase regions of the pol gene by RT-PCR and Sanger sequencing. Drug resistance mutation (DRM) interpretation reports the presence of mutations related to protease inhibitors (PIs), Nucleoside reverse-transcriptase inhibitors (NRTI) and Non-nucleoside reverse-transcriptase inhibitors (NNRTI) based on analysis using Stanford HIV database program...
January 2017: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/28094565/the-decline-in-hiv-1-drug-resistance-in-heavily-antiretroviral-experienced-patients-is-associated-with-optimized-prescriptions-in-a-treatment-roll-out-program-in-mexico
#13
Juan J Calva, Silvana Larrea, Marco A Tapia-Maltos, Mauricio Ostrosky-Frid, Carolina Lara, Pedro Aguilar-Salinas, Héctor Rivera, Juan P Ramírez
A decrease in the rate of acquired antiretroviral (ARV) drug-resistance (ADR) over time has been documented in high-income settings, but data on the determinants of this phenomenon are lacking. We tested the hypothesis that in heavily ARV-experienced patients in the Mexican ARV therapy (ART) roll-out program, the drop in ADR would be associated with changes in ARV drug usage. Genotypic resistance tests obtained from 974 HIV-infected patients with virologic failure and at least 2 previously failed ARV regimens from throughout the country were analyzed for the presence of nRTI, NNRTI and PI resistance-associated mutations (RAMs)...
January 17, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28088884/dual-raltegravir-etravirine-combination-as-maintenance-regimen-in-virologically-suppressed-hiv-1-infected-patients
#14
Leonardo Calza, Eleonora Magistrelli, Vincenzo Colangeli, Roberto Manfredi, Marco Borderi, Nicolò Rossi, Matteo Conti, Rita Mancini, Pierluigi Viale
BACKGROUND: Nucleoside reverse transcriptase inhibitor (NRTI)- and protease inhibitor (PI)-sparing antiretroviral regimens may be useful in selected HIV-infected patients with resistance or intolerance to these drug classes. METHODS: This was an observational prospective study of patients on suppressive antiretroviral therapy containing two NRTIs plus one ritonavir-boosted PI who switched to a dual regimen containing raltegravir plus etravirine. Patients were required not to have prior virological failure to raltegravir and to have efficacy of etravirine showed through the genotypic resistance assay in case of prior non-nucleoside reverse transcriptase inhibitor (NNRTI) virological failure...
January 15, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28042101/efavirenz-dissolution-enhancement-iii-colloid-milling-pharmacokinetics-and-electronic-tongue-evaluation
#15
Cristiane R D Hoffmeister, Cinira Fandaruff, Maíra A da Costa, Lucio M Cabral, Luciana R Pitta, Stanley E R Bilatto, Livia D Prado, Daniel S Corrêa, Leandro Tasso, Marcos Antônio S Silva, Helvécio V A Rocha
Efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor (NNRTI), is part of first-line therapy for the treatment of human immunodeficiency virus type 1 infection (HIV-1/AIDS). This drug shows relatively low oral absorption and bioavailability, as well as high intra- and inter-subject variability. Several studies have shown that treatment failure and adverse effects are associated with low and high EFV plasma concentrations, respectively. Some studies suggest different EFV formulations to minimize inter-patient variability and improve its solubility and dissolution; however, all of these formulations are complex, using for instance, cyclodextrins, dendrimers and polymeric nanoparticles, rendering them inviable industrially...
March 1, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28027281/virologic-response-to-first-line-efavirenz-or-nevirapine-based-anti-retroviral-therapy-in-hiv-infected-african-children
#16
Adeodata Kekitiinwa, Alexander J Szubert, Moira Spyer, Richard Katuramu, Victor Musiime, Tawanda Mhute, Sabrina Bakeera-Kitaka, Oscar Senfuma, Ann Sarah Walker, Diana M Gibb
BACKGROUND: Poorer virologic response to nevirapine vs efavirenz-based antiretroviral therapy (ART) has been reported in adult systematic reviews and pediatric studies. METHODS: We compared drug discontinuation and viral load (VL) response in ART-naïve Ugandan/Zimbabwean children ≥3 years of age initiating ART with clinician-chosen nevirapine vs efavirenz in the ARROW trial. Predictors of suppression <80, <400 and <1000 copies/ml at 36, 48 and 144 weeks were identified using multivariable logistic regression with backwards elimination (p=0...
December 23, 2016: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28017554/trends-and-predictors-of-hiv-1-acquired-drug-resistance-in-minas-gerais-brazil-2002-2012
#17
Helena Duani, Agdemir Waleria Aleixo, Unaí Tupinambás
Several studies show that the prevalence of multidrug-resistant HIV-1 virus is declining over time. A retrospective cohort study was carried out to evaluate the trends of drug resistance in antiretroviral treatment-exposed (ART) individuals in a state of a middle-income country, Minas Gerais, southeast region of Brazil. We analyzed 2115 HIV-1 sequences from 2002 up to 2012, from 52 cities of Minas Gerais. The groups were analyzed according to the definitions: "IAS - 3 class mutations", if ≥1 drug resistance mutation from IAS 2015 list (DRM) was present in each class; "No fully susceptible drugs" as the absence of any fully susceptible drug in Stanford algorithm; and "GSS≥2", when a maximum calculated GSS (genotypic susceptibility score) was ≥2 or ≥3, counting only drugs available in Brazil and USA at given calendar years...
December 22, 2016: Brazilian Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28010730/from-antiretroviral-therapy-access-to-provision-of-third-line-regimens-evidence-of-hiv-drug-resistance-mutations-to-first-and-second-line-regimens-among-ugandan-adults
#18
Ivan Namakoola, Ivan Kasamba, Billy N Mayanja, Patrick Kazooba, Joseph Lutaakome, Fred Lyagoba, Anne A Kapaata, Pontiano Kaleebu, Paula Munderi
BACKGROUND: HIV care programs in resource-limited settings have hitherto concentrated on antiretroviral therapy (ART) access, but HIV drug resistance is emerging. In a cross-sectional study of HIV-positive adults on ART for ≥6 months enrolled into a prospective cohort in Uganda, plasma HIV RNA was measured and genotyped if ≥1000 copies/ml. Identified Drug resistance mutations (DRMs) were interpreted using the Stanford database, 2009 WHO list of DRMs and the IAS 2014 update on DRMs, and examined and tabulated by ART drug classes...
December 23, 2016: BMC Research Notes
https://www.readbyqxmd.com/read/28008980/antiretroviral-treatment-with-efavirenz-disrupts-the-blood-brain-barrier-integrity-and-increases-stroke-severity
#19
Luc Bertrand, Levi Dygert, Michal Toborek
The introduction of antiretroviral drugs (ARVd) changed the prognosis of HIV infection from a deadly disease to a chronic disease. However, even with undetectable viral loads, patients still develop a wide range of pathologies, including cerebrovascular complications and stroke. It is hypothesized that toxic side effects of ARVd may contribute to these effects. To address this notion, we evaluated the impact of several non-nucleoside reverse transcriptase inhibitors (NNRTI; Efavirenz, Etravirine, Rilpivirine and Nevirapine) on the integrity of the blood-brain barrier, and their impact on severity of stroke...
December 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27999070/alarming-increase-in-pretreatment-hiv-drug-resistance-in-children-living-in-sub-saharan-africa-a-systematic-review-and-meta-analysis
#20
R S Boerma, K C E Sigaloff, A S Akanmu, S Inzaule, M Boele van Hensbroek, T F Rinke de Wit, J C Calis
BACKGROUND: Children have an augmented risk of pretreatment HIV drug resistance (PDR) due to exposure to antiretroviral drugs for the prevention of mother-to-child transmission (PMTCT). Paediatric data are essential to evaluate the effectiveness of the restricted number of paediatric regimens currently available, but these data are scarce. METHODS: We conducted a systematic review of the literature on PDR in children (median age ≤12 years) in sub-Saharan Africa...
December 20, 2016: Journal of Antimicrobial Chemotherapy
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