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https://www.readbyqxmd.com/read/28079946/enantioselective-and-regiodivergent-addition-of-purines-to-terminal-allenes-synthesis-of-abacavir
#1
Niels Thieme, Bernhard Breit
The rhodium-catalyzed atom-economic asymmetric N-selective intermolecular addition of purine derivatives to terminal allenes is reported. Branched allylic purines were obtained in high yields, regioselectivity and outstanding enantioselectivity utilizing a Rh/Josiphos catalyst. Conversely, linear selective allylation of purines could be realized in good to excellent regio- and E/Z-selectivity with a Pd/dppf catalyst system. Furthermore, the new methodology was applied to a straightforward asymmetric synthesis of carbocyclic nucleoside abacavir...
January 12, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28067719/insulin-resistance-and-markers-of-inflammation-in-hiv-infected-ugandan-children-in-the-chapas-3-trial
#2
Sahera Dirajlal-Fargo, Victor Musiime, Adrian Cook, Grace Mirembe, Julia Kenny, Ying Jiang, Sara Debanne, Nigel Klein, Grace A Mccomsey
BACKGROUND: Few studies have investigated metabolic complications in HIV-infected African children and their relation with inflammation. METHODS: We compared baseline and changes in insulin resistance (HOMA-IR) and in markers of inflammation over 48 weeks, in a subset of antiretroviral therapy (ART) naïve Ugandan children from the CHAPAS-3 trial randomized to zidovudine (AZT), stavudine (D4T) or abacavir (ABC) based regimens. Non-parametric methods were used to explore between and within group differences and multivariable analyses to assess associations of HOMA-IR...
January 6, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28065890/impact-of-obesity-on-antiretroviral-pharmacokinetics-and-immuno-virological-response-in-hiv-infected-patients-a-case-control-study
#3
Vincent Madelain, Minh P Le, Karen Champenois, Charlotte Charpentier, Roland Landman, Veronique Joly, Patrick Yeni, Diane Descamps, Yazdan Yazdanpanah, Gilles Peytavin
BACKGROUND: Obesity has high prevalence among HIV-infected patients. Increased adipose tissue mass affects the pharmacokinetics of numerous drugs, but few data are available for antiretroviral drugs. OBJECTIVES: In this study we aimed to explore the pharmacokinetics of antiretroviral drugs and the immuno-virological response in obese patients with HIV infection. PATIENTS AND METHODS: We examined data from 2009 to 2012 in our hospital's database for HIV-1-infected patients who received an antiretroviral drug (abacavir, emtricitabine, lamivudine, tenofovir, efavirenz, etravirine, nevirapine, atazanavir/ritonavir, darunavir/ritonavir, lopinavir/ritonavir or raltegravir)...
January 8, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28061820/associations-of-statins-and-antiretroviral-drugs-with-the-onset-of-type-2-diabetes-among-hiv-1-infected-patients
#4
Vincenzo Spagnuolo, Laura Galli, Andrea Poli, Stefania Salpietro, Nicola Gianotti, Piermarco Piatti, Francesca Cossarini, Concetta Vinci, Elisabetta Carini, Adriano Lazzarin, Antonella Castagna
BACKGROUND: Statin use is associated with a modest increase in the incidence of type 2 diabetes mellitus (DM) among the general population. However, HIV-infected patients have a higher risk of developing DM, and it is unclear whether statins have a diabetogenic effect in these patients. Therefore, we investigated the associations of statin use and exposure to antiretroviral drugs with type 2 DM onset in a cohort of HIV-infected patients. METHODS: This retrospective, controlled, cohort study identified HIV-1-infected patients who did not have DM and were not receiving statins at their antiretroviral treatment (ART) initiation...
January 7, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28060017/determinants-of-virological-outcome-and-adverse-events-in-african-children-treated-with-paediatric-nevirapine-fixed-dose-combination-tablets
#5
Andrzej Bienczak, Paolo Denti, Adrian Cook, Lubbe Wiesner, Veronica Mulenga, Cissy Kityo, Addy Kekitiinwa, Diana M Gibb, David Burger, A Sarah Walker, Helen Mcilleron
BACKGROUND: Nevirapine is the only non-nucleoside reverse transcriptase inhibitor currently available as a paediatric fixed-dose combination tablet and is widely used in African children. Nonetheless, the number of investigations into pharmacokinetic determinants of virological suppression in African children is limited and the predictive power of the current therapeutic range was never evaluated in this population, thereby limiting treatment optimisation. METHODS: We analysed data from 322 African children (aged 0...
January 4, 2017: AIDS
https://www.readbyqxmd.com/read/28057759/potent-nlrp3-inflammasome-activation-by-the-hiv-reverse-transcriptase-inhibitor-abacavir
#6
Atiye Toksoy, Helga Sennefelder, Christian Adam, Sonja Hofmann, Axel Trautmann, Matthias Goebeler, Marc Schmidt
There is experimental and clinical evidence that some exanthematous allergic drug hypersensitivity reactions are mediated by drug-specific T cells. We hypothesized that the capacity of certain drugs to directly stimulate the innate immune system may contribute to generate drug-specific T cells. Here we analyzed whether abacavir, an HIV-1 reverse transcriptase inhibitor often inducing severe delayed-type drug hypersensitivity, can trigger innate immune activation that may contribute to its allergic potential...
January 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28035758/genotypic-tropism-testing-of-proviral-dna-to-guide-maraviroc-initiation-in-aviraemic-subjects-48-week-analysis-of-results-from-the-protest-study
#7
E Poveda, J Hernández-Quero, M J Pérez-Elías, M A Ribas, O J Martínez-Madrid, J Flores, J Navarro, F Gutiérrez, M García-Deltoro, A Imaz, A Ocampo, A Artero, F Blanco, E Bernal, J Pasquau, C Mínguez-Gallego, N Pérez, A Aiestaran, F García, R Paredes
OBJECTIVES: Maraviroc (MVC) is a suitable drug for aviraemic subjects on antiretroviral treatment (ART) developing toxicity. Its prescription requires prior tropism testing. It is unknown if proviral DNA genotypic tropism testing is reliable for guiding MVC initiation in aviraemic subjects, so this study was carried out to address this issue. METHODS: PROTEST was a phase 4, prospective, single-arm clinical trial carried out in 24 HIV care centres in Spain. MVC-naïve HIV-1-infected patients with HIV-1 RNA < 50 copies/mL on stable ART during the previous 6 months who required an ART change because of toxicity and who had R5 HIV, as determined by proviral DNA genotypic tropism testing, initiated MVC with two nucleoside reverse transcriptase inhibitors (NRTIs) and were followed for 48 weeks...
December 30, 2016: HIV Medicine
https://www.readbyqxmd.com/read/28019192/lipid-lowering-effect-and-changes-in-estimated-cardiovascular-risk-after-switching-to-a-tenofovir-containing-regimen-for-the-treatment-of-hiv-infected-patients
#8
Roberta Gagliardini, Massimiliano Fabbiani, Manuela Colafigli, Alessandro D'Avino, Annalisa Mondi, Alberto Borghetti, Silvia Lamonica, Roberto Cauda, Andrea De Luca, Simona Di Giambenedetto
Tenofovir could have a direct lipid-lowering effect. The aim of our retrospective study was to investigate changes in cardiovascular risk after switching from a tenofovir-sparing to a tenofovir-containing backbone. Lipid parameters and cardiovascular risk [calculated using 10-years Framingham Risk Score (FRS) and 5-years DAD Risk Score (DRS)] were analysed at baseline and after three months. 273 patients were enrolled. After switching, significant decreases in total cholesterol (TC) (-8.2mg/dl, p < 0.001), LDL (-8...
December 26, 2016: Journal of Chemotherapy
https://www.readbyqxmd.com/read/28017537/human-leukocyte-antigen-and-idiosyncratic-adverse-drug-reactions
#9
REVIEW
Toru Usui, Dean J Naisbitt
A clinical association between a specific human leukocyte antigen (HLA) allele and idiosyncratic adverse drug reactions (IADRs) is a strong indication that IADRs are mediated by the adaptive immune system. For example, it is well-established that HLA-B*15:02 and HLA-B*57:01 are associated with carbamazepine-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and abacavir-induced hypersensitivity/flucloxacillin-induced liver injury, respectively. Drug-specific T-cells whose response is restricted by specific HLA risk alleles have been detected from IADR patients, also suggesting an adaptive immune pathogenesis...
November 18, 2016: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28008867/dolutegravir-plasma-concentrations-according-to-companion-antiretroviral-drug-unwanted-drug-interaction-or-desirable-boosting-effect
#10
Dario Cattaneo, Davide Minisci, Valeria Cozzi, Agostino Riva, Paola Meraviglia, Emilio Clementi, Massimo Galli, Cristina Gervasoni
BACKGROUND: Studies in healthy volunteers have shown that the recently approved HIV integrase inhibitor dolutegravir has limited drug-to-drug interaction profile. Here we carried out a pharmacokinetic survey in HIV-infected patients given dolutegravir as part of their antiretroviral therapy. METHODS: Dolutegravir plasma trough concentrations were measured in 78 HIV infected patients given the drug in combination with a protease inhibitor, a non nucleoside reverse transcriptase inhibitor or abacavir/lamivudine...
December 23, 2016: Antiviral Therapy
https://www.readbyqxmd.com/read/27999707/novel-concepts-for-drug-hypersensitivity-based-on-the-use-of-long-time-scale-molecular-dynamic-simulation
#11
Takahiro Murai, Norihito Kawashita, Yu-Shi Tian, Tatsuya Takagi
The discovery that several drug hypersensitivity reactions (DHRs) are associated with specific human leukocyte antigen (HLA) alleles has attracted increasing research interest. However, the underlying mechanisms of these HLA-induced DHRs remain unclear, especially for drug-induced immediate activation of T-cell clones (TCCs). Recently, a novel hypothesis involving partial detachment between self-peptide(s) and the HLA molecule (altered peptide-HLA (pHLA) model) has been proposed to explain these phenomena. In order to clarify this hypothesis, we performed long-timescale molecular dynamics (MD) simulations...
2016: Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27999056/switching-from-a-ritonavir-boosted-pi-to-dolutegravir-as-an-alternative-strategy-in-virologically-suppressed-hiv-infected-individuals
#12
Eugènia Negredo, Vicente Estrada, Pere Domingo, Maria Del Mar Gutiérrez, Gracia M Mateo, Jordi Puig, Anna Bonjoch, Arelly Ornelas, Patricia Echeverría, Carla Estany, Jessica Toro, Bonaventura Clotet
BACKGROUND: Switching from PIs to dolutegravir in virologically suppressed HIV-infected individuals has not been assessed. OBJECTIVES: The principal aim was to assess the evolution of bone mineral density (BMD) when switching from a ritonavir-boosted PI to dolutegravir in HIV-infected patients with osteopenia or osteoporosis. The secondary objective was to assess the antiviral efficacy and safety of the switch therapy. METHODS: This randomized, multicentre study assessed changes in BMD, bone turnover markers, and antiviral efficacy and safety in 73 virologically suppressed patients with osteopenia/osteoporosis taking a ritonavir-boosted PI plus abacavir/lamivudine who were randomized to switch from PI to dolutegravir (DOLU group, n = 37) or continue with a PI (PI group, n = 36)...
December 20, 2016: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27912079/a-humanized-mouse-model-for-hiv-2-infection-and-efficacy-testing-of-a-single-pill-triple-drug-combination-anti-retroviral-therapy
#13
Shuang Hu, Charles Preston Neff, Dipu Mohan Kumar, Yuichiro Habu, Sarah R Akkina, Takahiro Seki, Ramesh Akkina
While HIV-2 is a causative agent for AIDS in addition to the better studied HIV-1, there is currently no suitable animal model for experimental studies for HIV-2 infection and evaluating promising drugs in vivo. Here we evaluated humanized mice for their susceptibility to HIV-2 infection and tested a single-pill three drug formulation of anti-retrovirals (NRTIs abacavir and lamivudine, integrase inhibitor dolutegravir) (trade name, Triumeq(R)). Our results showed that hu-mice are susceptible to HIV-2 infection showing persistent viremia and CD4 T cell loss, key hallmarks of AIDS pathogenesis...
January 15, 2017: Virology
https://www.readbyqxmd.com/read/27904105/evaluation-of-the-lipid-concentrations-after-switching-from-antiretroviral-drug-tenofovir-disoproxil-fumarate-emtricitabine-to-abacavir-sulfate-lamivudine-in-virologically-suppressed-human-immunodeficiency-virus-infected-patients
#14
Hirotaka Arae, Masao Tateyama, Hideta Nakamura, Daisuke Tasato, Kaoru Kami, Kyoko Miyagi, Saori Maeda, Hitoshi Uehara, Makiko Moromi, Katsunori Nakamura, Jiro Fujita
Objective Recently, tenofovir disoproxil fumatate (TDF)-related side effects, such as renal nephrotoxicity and reduction of bone mineral density, have been reported. Consequently, increased switching from fixed-dose tablet TDF and emtricitabine (TDF/FTC) to abacavir and lamivudine (ABC/3TC) has occurred. Interestingly, while TDF has a lipid-lowering property, one of the ABC-related side effects is hyperlipidemia. Therefore, such switching could cause lipid elevation. To evaluate the change in lipid levels associated with switching from TDF/FTC to ABC/3TC in virologically-suppressed human immunodeficiency virus (HIV)-infected patients...
2016: Internal Medicine
https://www.readbyqxmd.com/read/27889293/stability-behaviour-of-antiretroviral-drugs-and-their-combinations-5-characterization-of-novel-degradation-products-of-abacavir-sulfate-by-mass-and-nuclear-magnetic-resonance-spectrometry
#15
Moolchand Kurmi, Archana Sahu, Saranjit Singh
In the present study, degradation behaviour of abacavir sulfate was evaluated in solution and solid stress conditions. Solution state studies resulted in formation of eleven degradation products; of which two were also formed on solid stress. The same were separated by high performance liquid chromatography. They were characterized using liquid chromatography-high resolution mass spectrometry, liquid chromatography-multistage mass spectrometry and hydrogen/deuterium exchange mass spectrometry data. Additionally, seven degradation products were isolated and subjected to 1D and 2D nuclear magnetic resonance studies for their structural confirmation...
February 5, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/27860104/higher-rates-of-neuropsychiatric-adverse-events-leading-to-dolutegravir-discontinuation-in-women-and-older-patients
#16
C Hoffmann, T Welz, M Sabranski, M Kolb, E Wolf, H-J Stellbrink, C Wyen
OBJECTIVES: Dolutegravir (DTG), a second-generation integrase strand transfer inhibitor (INSTI), is now among the most frequently used antiretroviral agents. However, recent reports have raised concerns about potential neurotoxicity. METHODS: We performed a retrospective analysis of a cohort of HIV-infected patients who had initiated an INSTI in two large German out-patient clinics between 2007 and 2016. We compared discontinuation rates because of adverse events (AEs) within 2 years of starting treatment with dolutegravir, raltegravir or elvitegravir/cobicistat...
January 2017: HIV Medicine
https://www.readbyqxmd.com/read/27846791/clinical-experience-with-dolutegravir-abacavir-lamivudine-in-hiv-hcv-co-infected-patients-treated-with-a-sofosbuvir-based-regimen-safety-and-efficacy
#17
Tamara M Johnson, Raymund Sison, James P Fallon, Prerak P Shukla, Sristi Bhattarai, Herbert Galang, Richard Habeeb, Jihad Slim
BACKGROUND: There is no known reason to suspect an adverse drug interaction between dolutegravir-based antiretroviral therapy and sofosbuvir, simeprevir, or ledipasvir. There is a paucity of clinical data for this combination. METHODS: Prospective, open-label study of patients with HIV well controlled on dolutegravir, abacavir, and lamivudine, who were co-infected with HCV genotype 1, and required therapy with simeprevir plus sofosbuvir or sofosbuvir/ledipasvir single-tablet regimen (STR) for 12 weeks...
November 2016: HIV Clinical Trials
https://www.readbyqxmd.com/read/27824625/intolerance-of-dolutegravir-containing-combination-antiretroviral-therapy-regimens-in-real-life-clinical-practice
#18
Mark G J de Boer, Guido E L van den Berk, Natasja van Holten, Josephine E Oryszcyn, Willemien Dorama, Daoud Ait Moha, Kees Brinkman
OBJECTIVE: Dolutegravir (DGV) is one of the preferred antiretroviral agents in first-line combination antiretroviral therapy (cART). Though considered to be a well tolerated drug, we aimed to determine the actual rate, timing and detailed motivation of stopping DGV in a real-life clinical setting. DESIGN: A cohort study including all patients who started DGV in two HIV treatment centers in The Netherlands. METHODS: All cART-naïve and cART-experienced patients who had started DGV were identified from the institutional HIV databases...
November 28, 2016: AIDS
https://www.readbyqxmd.com/read/27815125/meeting-report-29th-international-conference-on-antiviral-research-in-la-jolla-ca-usa
#19
REVIEW
R Anthony Vere Hodge
The 29th International Conference on Antiviral Research (ICAR) was held in La Jolla, CA, USA from April 17 to 21, 2016. This report opens with a tribute to the late Chris McGuigan, a Past-President of ISAR, then continues with summaries of the principal invited lectures. Doug Richman (Elion Award) investigated HIV resistance, Bob Vince (Holý Award) showed how carbocyclic nucleoside analogs led to abacavir and Jerome Deval (Prusoff Award) explained how his group chose to seek a nucleoside analog to treat RSV...
January 2017: Antiviral Research
https://www.readbyqxmd.com/read/27804313/antiretroviral-treatment-for-hiv-infection-swedish-recommendations-2016
#20
Jaran Eriksen, Jan Albert, Anders Blaxhult, Christina Carlander, Leo Flamholc, Magnus Gisslén, Filip Josephson, Olof Karlström, Lars Navér, Veronica Svedhem, Aylin Yilmaz, Anders Sönnerborg
The Swedish Medical Products Agency and the Swedish Reference Group for Antiviral Therapy (RAV) have jointly published recommendations for the treatment of HIV infection on seven previous occasions (2002, 2003, 2005, 2007, 2009, 2011 and 2014). In February 2016, an expert group under the guidance of RAV once more revised the guidelines. The most important updates in the present guidelines are as follows: Tenofovir alafenamide (TAF) has recently been registered. TAF has several advantages over tenofovir disoproxilfumarate (TDF) and is recommended instead of TDF in most cases...
January 2017: Infectious Diseases
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