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https://www.readbyqxmd.com/read/28923862/antiviral-activity-of-bictegravir-and-cabotegravir-against-integrase-inhibitor-resistant-sivmac239-and-hiv-1
#1
Said A Hassounah, Ahmad Alikhani, Maureen Oliveira, Simrat Bharaj, Ruxandra-Ilinca Ibanescu, Nathan Osman, Hong-Tao Xu, Bluma G Brenner, Thibault Mesplède, Mark A Wainberg
Animal models are essential to study novel antiretroviral drugs, resistance-associated mutations (RAMs), and treatment strategies. Bictegravir (BIC) is a novel potent integrase (IN) strand transfer inhibitor (INSTI) that has shown promising results against HIV-1 infection in vitro and in vivo and against clinical isolates with resistance against INSTIs. BIC has a higher genetic barrier to the development of resistance than two clinically approved INSTIs termed raltegravir and elvitegravir. Another clinically approved INSTI, dolutegravir (DTG) also possesses a high genetic barrier to resistance while a fourth compound termed cabotegravir (CAB) is currently in late phases of clinical development...
September 18, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28905173/pharmacokinetic-and-tissue-distribution-profile-of-long-acting-tenofovir-alafenamide-and-elvitegravir-loaded-nanoparticles-in-humanized-mice-model
#2
Pavan Kumar Prathipati, Subhra Mandal, Gregory Pon, Renuga Vivekanandan, Christopher J Destache
PURPOSE: Non-adherence to the antiretroviral (ARV) regimen is a critical factor in determining efficacy of ARV drugs for pre-exposure prophylaxis (PrEP). A long-acting parenteral formulation may be an effective alternative to daily oral dosing. A pharmacokinetic and tissue distribution study of drug-loaded nanoparticle (NP) was performed in female humanized CD34(+)-NSG mice. METHODS: Mice received 200 mg/kg each of tenofovir alafenamide (TAF) and elvitegravir (EVG) as free drugs (TAF + EVG solution) or as drug loaded NP (TAF + EVG NP) formulation by subcutaneous (SubQ) administration...
September 13, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28895486/iatrogenic-adrenal-insufficiency-secondary-to-combination-therapy-with-elvitegravir-cobicistat-tenofovir-disoproxil-fumarate-emtricitabine-and-interlaminar-triamcinolone-injection-in-an-aids-patient
#3
Chanie Wassner, Sutapa Maiti, Kurt Kodroff, Henry Cohen
We report the first identified case of suspected iatrogenic adrenal insufficiency after an interlaminar injection of triamcinolone acetonide while on concomitant Stribild (elvitegravir 150 mg/cobicistat 150 mg/tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg [EVG/c/TDF/FTC]). A 49-year-old female with HIV on EVG/c/TDF/FTC therapy presented to our endocrinology clinic to be evaluated for suspected Cushing syndrome. Prior to presentation, the patient had been given 2 interlaminar spinal injections of triamcinolone...
January 1, 2017: Journal of the International Association of Providers of AIDS Care
https://www.readbyqxmd.com/read/28891788/week-48-resistance-analysis-of-elvitegravir-cobicistat-emtricitabine-tenofovir-df-versus-atazanavir-ritonavir-emtricitabine-tenofovir-df-in-hiv-1-infected-women-waves-study-gs-us-236-0128
#4
Rima Kulkarni, Sally L Hodder, Huyen Cao, Silvia Chang, Michael D Miller, Kirsten L White
Background Women and those with non-B subtype HIV-1 are typically underrepresented in clinical trials. WAVES (GS-US-236-0128) was a double-blind phase 3b study among treatment-naïve HIV-1-infected women that demonstrated that elvitegravir/cobicistat/emtricitabine/tenofovir DF (EVG/COBI/FTC/TDF; N = 289) was superior to atazanavir + ritonavir + FTC/TDF (ATV + RTV + FTC/TDF; N = 286) for HIV-1 RNA < 50 copies/mL by FDA snapshot analysis at week 48. Here, we describe resistance development through week 48 in women with virologic failure and determine the impact of pre-existing mutations and HIV-1 subtype on viral suppression...
July 2017: HIV Clinical Trials
https://www.readbyqxmd.com/read/28890836/new-diagnosis-of-aids-based-on-salmonella-enterica-subsp-i-enterica-enteritidis-a-meningitis-in-a-previously-immunocompetent-adult-in-the-united-states
#5
Andrew C Elton, James Levin, Matthew P Lazio
Salmonella meningitis is a rare manifestation of meningitis typically presenting in neonates and the elderly. This infection typically associates with foodborne outbreaks in developing nations and AIDS-endemic regions. We report a case of a 19-year-old male presenting with altered mental status after 3-day absence from work at a Wisconsin tourist area. He was febrile, tachycardic, and tachypneic with a GCS of 8. The patient was intubated and a presumptive diagnosis of meningitis was made. Treatment was initiated with ceftriaxone, vancomycin, acyclovir, dexamethasone, and fluid resuscitation...
2017: Case Reports in Infectious Diseases
https://www.readbyqxmd.com/read/28868001/efficacy-and-tolerability-of-polyphenon-e-in-difficult-to-treat-multiple-genital-warts-in-an-hiv-positive-male-subject
#6
Mauro Grandolfo, Massimo Milani
A 55-year-old man, nonsmoker, with a HIV-positive history came to our attention in February 2017. He was on treatment with Stribild(TM), 1 capsule daily (150 mg elvitegravir, 150 mg cobicistat, 200 mg emtricitabine, and 245 mg tenofovir disoproxil). The CD4+/CD8+ cellular count was 326/µL (normal values: 404-1,612); the CD3+/CD8+ cellular count was 819/µL (normal values: 220-1,219). The CD4/CD8 ratio was 0.40 (normal value: >1). Several typical genital wart lesions were present at the penis shaft and at the level of the neck and the corona of glans...
May 2017: Case Reports in Dermatology
https://www.readbyqxmd.com/read/28861811/differential-effects-of-antiretroviral-drugs-on-neurons-in-vitro-roles-for-oxidative-stress-and-integrated-stress-response
#7
Anna L Stern, Rebecca N Lee, Nina Panvelker, Jiean Li, Jenna Harowitz, Kelly L Jordan-Sciutto, Cagla Akay-Espinoza
Mounting evidence suggests that antiretroviral drugs may contribute to the persistence of HIV-associated neurocognitive disorders (HAND), which impact 30%-50% of HIV-infected patients in the post-antiretroviral era. We previously reported that two first generation HIV protease inhibitors, ritonavir and saquinavir, induced oxidative stress, with subsequent neuronal death in vitro, which was reversed by augmentation of the endogenous antioxidant response by monomethyl fumarate. We herein determined whether two newer-generation PIs, darunavir and lopinavir, were deleterious to neurons in vitro...
August 31, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28859447/hiv-1-non-group-m-phenotypic-susceptibility-to-integrase-strand-transfer-inhibitors
#8
E Alessandri-Gradt, G Collin, A Tourneroche, M Bertine, M Leoz, C Charpentier, G Unal, D Descamps, J C Plantier
Objectives: To determine natural phenotypic susceptibility of non-group M HIV-1 to integrase strand transfer inhibitors (INSTIs) in a large panel of 39 clinical strains from groups O, N and P and to identify genotypic polymorphisms according to susceptibility levels. Methods: Susceptibility to raltegravir, elvitegravir and dolutegravir was evaluated in 36 HIV-1/O, 2 HIV-1/N and 1 HIV-1/P strains plus an HIV-1/M reference strain. IC50 values were determined after 3 days, and fold changes (FCs) were calculated relative to the HIV-1/M strain...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28829952/degradable-bioadhesive-nanoparticles-for-prolonged-intravaginal-delivery-and-retention-of-elvitegravir
#9
Muneeb Mohideen, Elias Quijano, Eric Song, Yang Deng, Gauri Panse, Wei Zhang, Meredith R Clark, W Mark Saltzman
New methods for long-lasting protection against sexually transmitted disease, such as the human immunodeficiency virus (HIV), are needed to help reduce the severity of STD epidemics, especially in developing countries. Intravaginal delivery of therapeutics has emerged as a promising strategy to provide women with local protection, but residence times of such agents are greatly reduced by the protective mucus layer, fluctuating hormone cycle, and complex anatomical structure of the reproductive tract. Polymeric nanoparticles (NPs) capable of encapsulating the desired cargo, penetrating through the mucosal surfaces, and delivering agents to the site of action have been explored...
November 2017: Biomaterials
https://www.readbyqxmd.com/read/28825943/weight-gain-in-persons-with-hiv-switched-from-efavirenz-based-to-integrase-strand-transfer-inhibitor-based-regimens
#10
Jamison Norwood, Megan Turner, Carmen Bofill, Peter Rebeiro, Bryan Shepherd, Sally Bebawy, Todd Hulgan, Stephen Raffanti, David W Haas, Timothy R Sterling, John R Koethe
BACKGROUND: With the introduction of integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART), persons living with HIV have a potent new treatment option. Recently, providers at our large treatment clinic noted weight gain in several patients switched from efavirenz/tenofovir disoproxil fumarate/emtricitabine (EFV/TDF/FTC) to dolutegravir/abacavir/lamivudine (DTG/ABC/3TC). In this study, we evaluated weight change in patients with sustained virologic suppression switched from EFV/TDF/FTC to an INSTI-containing regimen...
August 18, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28790862/hyperbilirubinemia-in-atazanavir-treated-hiv-infected-patients-the-impact-of-the-ugt1a1-28-allele
#11
REVIEW
Periklis Panagopoulos, Efstathios Maltezos, Angelos Hatzakis, Dimitrios Paraskevis
Combination antiretroviral treatment (cART) has significantly improved the life expectancy of people living with HIV. The life-long nature of cART increases the risk of side effects, which in some cases may have been caused by specific genetic characteristics. Patients treated with atazanavir (ATV) boosted with ritonavir (rit), which is a protease inhibitor used for the treatment of HIV, present with elevated bilirubin levels, at high proportions. ATV/rit-related hyperbilirubinemia has been previously associated with genetic characteristics in uridine diphosphate glucuronosyltransferase (UGT) enzyme...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28762239/high-performance-liquid-chromatography-tandem-mass-spectrometry-for-simultaneous-determination-of-raltegravir-dolutegravir-and-elvitegravir-concentrations-in-human-plasma-and-cerebrospinal-fluid-samples
#12
Kiyoto Tsuchiya, Mayu Ohuchi, Naoe Yamane, Hiroaki Aikawa, Hiroyuki Gatanaga, Shinichi Oka, Akinobu Hamada
A simple sample treatment procedure and sensitive liquid chromatography-tandem mass spectrometry method were developed for the simultaneous quantification of the concentrations of human immunodeficiency virus-1 integrase strand transfer inhibitors - raltegravir, dolutegravir and elvitegravir - in human plasma and cerebrospinal fluid (CSF). Plasma and CSF samples (20 μL each) were deproteinized with acetonitrile. Raltegravir-d3 was used as the internal standard. Chromatographic separation was achieved on an XBridge C18 column (50 × 2...
July 31, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28753637/collaborative-update-of-a-rule-based-expert-system-for-hiv-1-genotypic-resistance-test-interpretation
#13
Roger Paredes, Philip L Tzou, Gert van Zyl, Geoff Barrow, Ricardo Camacho, Sergio Carmona, Philip M Grant, Ravindra K Gupta, Raph L Hamers, P Richard Harrigan, Michael R Jordan, Rami Kantor, David A Katzenstein, Daniel R Kuritzkes, Frank Maldarelli, Dan Otelea, Carole L Wallis, Jonathan M Schapiro, Robert W Shafer
INTRODUCTION: HIV-1 genotypic resistance test (GRT) interpretation systems (IS) require updates as new studies on HIV-1 drug resistance are published and as treatment guidelines evolve. METHODS: An expert panel was created to provide recommendations for the update of the Stanford HIV Drug Resistance Database (HIVDB) GRT-IS. The panel was polled on the ARVs to be included in a GRT report, and the drug-resistance interpretations associated with 160 drug-resistance mutation (DRM) pattern-ARV combinations...
2017: PloS One
https://www.readbyqxmd.com/read/28741965/cost-effectiveness-of-dolutegravir-abacavir-lamivudine-in-hiv-1-treatment-naive-tn-patients-in-france
#14
Gilles Pialoux, Anne-Geneviève Marcelin, Hélène Cawston, Caroline Guilmet, Laurent Finkielsztejn, Audrey Laurisse, Céline Aubin
BACKGROUND: To evaluate the cost-effectiveness of an integrase inhibitor (INI), dolutegravir (DTG), in combination with abacavir (ABC)/lamivudine (3TC) in France, in treatment-naive (TN) HIV adult patients. METHODS: The ARAMIS microsimulation Markov model, evaluates costs and effects of DTG vs. first-line ARVs options including INIs (raltegravir, elvitegravir/c), protease inhibitors (PIs) (darunavir/r, atazanavir/r, lopinavir/r), non-nucleoside reverse transcriptase inhibitors (efavirenz and rilpivirine)...
July 31, 2017: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/28741582/prevalence-of-drug-drug-interactions-in-the-era-of-hiv-integrase-inhibitors-a-retrospective-clinical-study
#15
C Baecke, I C Gyssens, L Decoutere, J C H van der Hilst, P Messiaen
BACKGROUND: Antiretroviral agents pose a high risk for drug-drug interactions (DDIs), mainly but not limited to being a substrate, inducer or inhibitor of P450 cytochrome enzymes. In part metabolised by other pathways, integrase inhibitors might show a more favourable profile. The aim of this study was to investigate the prevalence of DDIs in daily clinical practice for patients starting different antiretroviral treatment (ART) regimens. METHODS: All patients starting ART in our centre from January 2009 to April 2016 were included...
July 2017: Netherlands Journal of Medicine
https://www.readbyqxmd.com/read/28737946/structure-guided-optimization-of-hiv-integrase-strand-transfer-inhibitors
#16
Xue Zhi Zhao, Steven J Smith, Daniel P Maskell, Mathieu Métifiot, Valerie E Pye, Katherine Fesen, Christophe Marchand, Yves Pommier, Peter Cherepanov, Stephen H Hughes, Terrence R Burke
Integrase mutations can reduce the effectiveness of the first-generation FDA-approved integrase strand transfer inhibitors (INSTIs), raltegravir (RAL) and elvitegravir (EVG). The second-generation agent, dolutegravir (DTG), has enjoyed considerable clinical success; however, resistance-causing mutations that diminish the efficacy of DTG have appeared. Our current findings support and extend the substrate envelope concept that broadly effective INSTIs can be designed by filling the envelope defined by the DNA substrates...
September 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28696345/optimal-hiv-postexposure-prophylaxis-regimen-completion-with-single-tablet-daily-elvitegravir-cobicistat-tenofovir-disoproxil-fumarate-emtricitabine-compared-with-more-frequent-dosing-regimens
#17
COMPARATIVE STUDY
Kenneth H Mayer, Daniel Jones, Catherine Oldenburg, Sachin Jain, Marcy Gelman, Shayne Zaslow, Chris Grasso, Matthew J Mimiaga
STRUCTURE: The study evaluated elvitegravir/cobicistat/tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) ("Quad pill") for postexposure prophylaxis (PEP). BACKGROUND: HIV-exposed individuals may benefit from PEP, but completion rates have been suboptimal because of regimen complexity and side effects. Newer antiretroviral combinations coformulated as single daily pills may optimize PEP adherence. SETTING: One hundred HIV-uninfected individuals who presented to a Boston community health center after an acute HIV sexual exposure were enrolled and initiated PEP with the daily, single-pill combination Quad pill for a 28-day course...
August 15, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28689453/switching-to-the-single-tablet-regimen-of-elvitegravir-cobicistat-emtricitabine-and-tenofovir-df-from-non-nucleoside-reverse-transcriptase-inhibitor-plus-coformulated-emtricitabine-and-tenofovir-df-regimens-week-96-results-of-strategy-nnrti
#18
Anton Pozniak, Jason Flamm, Andrea Antinori, Mark Bloch, Douglas Ward, Juan Berenguer, Pierre Cote, Kristen Andreatta, William Garner, Javier Szwarcberg, Thai Nguyen-Cleary, Damian J McColl, David Piontkowsky
BACKGROUND: HIV-1-infected, virologically suppressed adults wanting to simplify or change their non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens may benefit from switching to the single-tablet regimen of elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (E/C/F/TDF). OBJECTIVE: We examined differences in the proportion of participants with HIV-1 RNA < 50 copies/mL (Snapshot analysis), change in CD4 cell count, safety, and patient-reported outcomes in participants switching to E/C/F/TDF from an NNRTI + FTC/TDF (TVD) regimen...
July 9, 2017: HIV Clinical Trials
https://www.readbyqxmd.com/read/28664752/comment-extensive-bruising-and-elevated-rivaroxaban-plasma-concentration-in-a-patient-receiving-cobicistat-boosted-elvitegravir
#19
Jamielynn C Sebaaly, Denise Kelley
No abstract text is available yet for this article.
June 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28650901/application-of-quality-by-design-approach-to-bioanalysis-development-of-a-method-for-elvitegravir-quantification-in-human-plasma
#20
Sara Baldelli, Giorgio Marrubini, Dario Cattaneo, Emilio Clementi, Matteo Cerea
BACKGROUND: The application of Quality by Design (QbD) principles in clinical laboratories can help to develop an analytical method through a systematic approach, providing a significant advance over the traditional heuristic and empirical methodology. In this work, we applied for the first time the QbD concept in the development of a method for drug quantification in human plasma using elvitegravir as the test molecule. METHODS: The goal of the study was to develop a fast and inexpensive quantification method, with precision and accuracy as requested by the European Medicines Agency guidelines on bioanalytical method validation...
October 2017: Therapeutic Drug Monitoring
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