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Dolutegravir

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https://www.readbyqxmd.com/read/28212411/lack-of-impact-of-pre-existing-t97a-hiv-1-integrase-mutation-on-integrase-strand-transfer-inhibitor-resistance-and-treatment-outcome
#1
Michael E Abram, Renee R Ram, Nicolas A Margot, Tiffany L Barnes, Kirsten L White, Christian Callebaut, Michael D Miller
T97A is an HIV-1 integrase polymorphism associated with integrase strand transfer inhibitor (INSTI) resistance. Using pooled data from 16 clinical studies, we investigated the prevalence of T97A (pre-existing and emergent) and its impact on INSTI susceptibility and treatment response in INSTI-naive patients who enrolled on elvitegravir (EVG)- or raltegravir (RAL)-based regimens. Prior to INSTI-based therapy, primary INSTI resistance-associated mutations (RAMs) were absent and T97A pre-existed infrequently (1...
2017: PloS One
https://www.readbyqxmd.com/read/28207816/hiv-drug-therapy-duration-a-swedish-real-world-nationwide-cohort-study-on-infcarehiv-2009-2014
#2
Amanda Häggblom, Stefan Lindbäck, Magnus Gisslén, Leo Flamholc, Bo Hejdeman, Andreas Palmborg, Amy Leval, Eva Herweijer, Sverrir Valgardsson, Veronica Svedhem
BACKGROUND: As HIV infection needs a lifelong treatment, studying drug therapy duration and factors influencing treatment durability is crucial. The Swedish database InfCareHIV includes high quality data from more than 99% of all patients diagnosed with HIV infection in Sweden and provides a unique opportunity to examine outcomes in a nationwide real world cohort. METHODS: Adult patients who started a new therapy defined as a new 3rd agent (all antiretrovirals that are not N[t]RTIs) 2009-2014 with more than 100 observations in treatment-naive or treatment-experienced patients were included...
2017: PloS One
https://www.readbyqxmd.com/read/28198203/enteral-administration-of-twice-daily-dolutegravir-and-rilpivirine-as-a-part-of-a-triple-therapy-regimen-in-a-critically-ill-patient-with-hiv
#3
Sarah Lynn Turley, Patricia Pecora Fulco
The administration of antiretroviral therapy (ART) in intubated critically ill patients may be challenging. Limited pharmacokinetic data exist characterizing the effects of crushed ART with subsequent enteral administration on antiretroviral drug concentrations or the clinical impact on HIV virologic suppression. We report a case of a 27-year-old HIV-positive male with presumed multidrug-resistant HIV and a diagnosis of lymphoma who required enteral ART administration after intensive care unit admission. Crushed twice-daily dolutegravir (separated from enteral nutrition by 2 hours) and rilpivirine (concurrently with a bolus feed) were administered via an orogastric tube...
January 1, 2017: Journal of the International Association of Providers of AIDS Care
https://www.readbyqxmd.com/read/28185217/erratum-to-a-two-way-steady-state-pharmacokinetic-interaction-study-of-doravirine-mk-1439-and-dolutegravir
#4
Matt S Anderson, Sauzanne Khalilieh, Ka Lai Yee, Rachael Liu, Li Fan, Matthew L Rizk, Vedangi Shah, Azra Hussaini, Ivy Song, Lisa L Ross, Joan R Butterton
No abstract text is available yet for this article.
February 10, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28168828/relative-bioavailability-of-a-dolutegravir-dispersible-tablet-and-the-effects-of-low-and-high-mineral-content-water-on-the-tablet-in-healthy-adults
#5
Ann M Buchanan, Michael Holton, Ian Conn, Mark Davies, Mike Choukour, Brian R Wynne
Dolutegravir (DTG) is approved in the United States to treat HIV-1-infected patients weighing ≥30 kg. A dispersible DTG tablet formulation was recently developed for pediatric patients. This study compares the pharmacokinetics (PK) of the dispersible tablet with that of a previously evaluated granule formulation. In this randomized, open-label, crossover study, 15 healthy adults received single oral doses of DTG 20 mg every 7 days across 5 treatment arms: granules consumed immediately after mixture with purified water, dispersible DTG consumed immediately after reconstitution in low-mineral-content (LMC) or high-mineral-content (HMC) water, and dispersible DTG consumed 30 minutes after dispersal in LMC or HMC water...
February 7, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28134625/autophagy-facilitates-macrophage-depots-of-sustained-release-nanoformulated-antiretroviral-drugs
#6
Divya Prakash Gnanadhas, Prasanta K Dash, Brady Sillman, Aditya N Bade, Zhiyi Lin, Diana L Palandri, Nagsen Gautam, Yazen Alnouti, Harris A Gelbard, JoEllyn McMillan, R Lee Mosley, Benson Edagwa, Howard E Gendelman, Santhi Gorantla
Long-acting anti-HIV products can substantively change the standard of care for patients with HIV/AIDS. To this end, hydrophobic antiretroviral drugs (ARVs) were recently developed for parenteral administration at monthly or longer intervals. While shorter-acting hydrophilic drugs can be made into nanocarrier-encased prodrugs, the nanocarrier encasement must be boosted to establish long-acting ARV depots. The mixed-lineage kinase 3 (MLK-3) inhibitor URMC-099 provides this function by affecting autophagy. Here, we have shown that URMC-099 facilitates ARV sequestration and its antiretroviral responses by promoting the nuclear translocation of the transcription factor EB (TFEB)...
January 30, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28127144/a-nodular-ulcerative-form-of-secondary-syphilis-in-aids
#7
Ofelya Gevorgyan, Benjamin D Owen, Arvind Balavenkataraman, Mitchell R Weinstein
An uncommon variant in the pre-AIDS era, lues maligna is a nodular-ulcerative form of secondary syphilis. We present a case of a 41-year-old man with HIV infection who developed fever, chills, nausea, vomiting, right upper quadrant abdominal pain, weight loss, watery diarrhea, and a painless, nonpruritic rash. He had diffuse nodular-ulcerative lesions in various stages of development. He was found to have a CD4 count of 101 cells/mm(3) (22%), an HIV viral load of 2,735,060 copies/mL, and a positive rapid plasma reagin at 1:64...
January 2017: Proceedings of the Baylor University Medical Center
https://www.readbyqxmd.com/read/28118801/early-clinical-experience-of-dolutegravir-in-an-hiv-cohort-in-a-larger-teaching-hospital
#8
Sej Todd, P Rafferty, E Walker, M Hunter, W W Dinsmore, C M Donnelly, E J McCarty, S P Quah, C R Emerson
Dolutegravir (DTG) is the third HIV integrase inhibitor (INI) available for prescription in Belfast since July 2014. It has shown high virological efficacy in both treatment-naïve and -experienced patients. We carried out a retrospective case chart analysis of HIV-1-positive adults commenced on DTG between July 2014 and September 2015. Patients were identified from records as either treatment-naïve or antiretroviral therapy (ART) experienced. Outcomes included: (1) virological response (HIV-1 RNA viral load at 0, 4, 8 and 12 weeks), (2) immunological response (CD4+ cell count at 0, 4, 8 and 12 weeks) and (3) tolerability (side effects and discontinuation)...
January 1, 2017: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/28114188/how-relevant-is-the-interaction-between-dolutegravir-and-metformin-in-real-life
#9
Cristina Gervasoni, Davide Minisci, Emilio Clementi, Giuliano Rizzardini, Dario Cattaneo
No abstract text is available yet for this article.
January 20, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28079545/efficacy-and-tolerability-of-dolutegravir-and-two-nucleos-t-ide-reverse-transcriptase-inhibitors-in-hiv-1-positive-virologically-suppressed-patients
#10
Alberto Borghetti, Gianmaria Baldin, Amedeo Capetti, Gaetana Sterrantino, Stefano Rusconi, Alessandra Latini, Andrea Giacometti, Giordano Madeddu, Chiara Picarelli, Ramona De Marco, Maria V Cossu, Filippo Lagi, Roberto Cauda, Andrea De Luca, Simona Di Giambenedetto
No abstract text is available yet for this article.
January 28, 2017: AIDS
https://www.readbyqxmd.com/read/28079544/discontinuation-of-treatment-and-adverse-events-in-an-italian-cohort-of-patients-on-dolutegravir
#11
Paolo Bonfanti, Giordano Madeddu, Roberto Gulminetti, Nicola Squillace, Giancarlo Orofino, Paola Vitiello, Stefano Rusconi, Benedetto M Celesia, Paolo Maggi, Elena Ricci
No abstract text is available yet for this article.
January 28, 2017: AIDS
https://www.readbyqxmd.com/read/28051809/pregnancy-related-changes-of-antiretroviral-pharmacokinetics-an-argument-for-tdm
#12
Francesco R Simonetti, Dario Cattaneo, Nadia Zanchetta, Vania Giacomet, Valeria Micheli, Nadia Ciminera, Cristina Gervasoni
Here we describe a case of an HIV-infected young woman with extensive drug-resistant virus, who was successfully switched from a raltegravir-based regimen to a dolutegravir-based intensified antiretroviral regimen a few days before scheduled caesarean section because of the still detectable viral load. The trough concentrations of all antiretroviral drugs before and after delivery are also described.Our case underlines both the difficult management of young women, HIV-infected at young age with very limited treatment options and the great variability in the pregnancy-related physiologic changes affecting the pharmacokinetics of antiretrovirals...
January 4, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28008867/dolutegravir-plasma-concentrations-according-to-companion-antiretroviral-drug-unwanted-drug-interaction-or-desirable-boosting-effect
#13
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/27999056/switching-from-a-ritonavir-boosted-pi-to-dolutegravir-as-an-alternative-strategy-in-virologically-suppressed-hiv-infected-individuals
#14
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/27999055/unravelling-the-dynamics-of-selection-of-multiresistant-variants-to-integrase-inhibitors-in-an-hiv-1-infected-child-using-ultra-deep-sequencing
#15
Karl Stefic, Maud Salmona, Marisa Capitao, Marion Splittgerber, Zoha Maakaroun-Vermesse, Marie-Laure Néré, Louis Bernard, Marie-Laure Chaix, Francis Barin, Constance Delaugerre
BACKGROUND: Ultra-deep sequencing (UDS) allows detection of minority resistant variants (MRVs) with a threshold of 1% and could be useful to identify variants harbouring single or multiple drug-resistance mutations (DRMs). OBJECTIVES: We analysed the integrase gene region longitudinally using UDS in an HIV-1-infected child rapidly failing a raltegravir-based regimen. METHODS: Longitudinal plasma samples at baseline and weeks 4, 8, 13, 17 and 39 were obtained, as well as the mother's baseline plasma sample...
December 20, 2016: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27999017/efficacy-and-tolerance-of-dolutegravir-based-combined-art-in-perinatally-hiv-1-infected-adolescents-a-french-multicentre-retrospective-study
#16
Coralie Briand, Catherine Dollfus, Albert Faye, Elie Kantor, Véronique Avettand-Fenoel, Marion Caseris, Diane Descamps, Véronique Schneider, Marie-Dominique Tabone, Geneviève Vaudre, Florence Veber, Stéphane Blanche, Pierre Frange
OBJECTIVES: To assess the safety and efficacy of a dolutegravir-based regimen in perinatally HIV-1-infected adolescents. PATIENTS AND METHODS: We conducted a retrospective multicentre study of 50 adolescents beginning dolutegravir-based treatment regimens between January 2014 and December 2015. Clinical and biological data collected before and after dolutegravir initiation were analysed. The primary endpoint was the proportion of patients achieving a plasma viral load (PVL) <50 copies/mL within 3 months of dolutegravir initiation (for patients with detectable viraemia at baseline) and maintaining virological suppression (PVL <50 copies/mL) until the last follow-up visit (for all patients)...
December 20, 2016: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27999010/pharmacokinetics-of-dolutegravir-and-rilpivirine-in-combination-with-simeprevir-and-sofosbuvir-in-hiv-hepatitis-c-virus-coinfected-patients-with-liver-cirrhosis
#17
Marco Merli, Laura Galli, Letizia Marinaro, Alessandra Ariaudo, Emanuela Messina, Caterina Uberti-Foppa, Antonella Castagna, Antonio D'Avolio, Adriano Lazzarin, Stefano Bonora, Hamid Hasson
OBJECTIVES: To evaluate the plasma trough concentrations (Ctrough) of dolutegravir and rilpivirine used in combination with simeprevir and sofosbuvir in HIV/hepatitis C virus (HCV)-coinfected patients with liver cirrhosis. Virological efficacy and safety of both ART and anti-HCV therapy were assessed. PATIENTS AND METHODS: A prospective observational study in HIV/HCV-coinfected patients with liver cirrhosis on ART with dolutegravir plus rilpivirine and treated with simeprevir plus sofosbuvir (±ribavirin) was conducted...
December 20, 2016: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27984559/psychiatric-symptoms-in-patients-receiving-dolutegravir
#18
Anna Fettiplace, Chris Stainsby, Alan Winston, Naomi Givens, Sarah Puccini, Vani Vannappagari, Ricky Hsu, Jennifer Fusco, Romina Quercia, Michael Aboud, Lloyd Curtis
INTRODUCTION: Psychiatric symptoms are reported to occur frequently in people living with HIV and may be associated with specific antiretrovirals. We analysed psychiatric symptoms observed with dolutegravir and other frequently prescribed anchor drugs. METHODS: Selected psychiatric symptoms (insomnia, anxiety, depression, and suicidality) occurring in HIV-positive patients during dolutegravir treatment across 5 randomized clinical trials (3 double-blind), in the Observational Pharmaco-Epidemiology Research & Analysis (OPERA®) cohort, and among cases spontaneously reported to ViiV Healthcare were analysed...
December 7, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/27977411/dolutegravir-monotherapy-when-should-clinical-practice-be-clinical-research
#19
Joel Gallant, Jeremy Sugarman
No abstract text is available yet for this article.
December 15, 2016: Antiviral Therapy
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
#20
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
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