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Dolutegravir

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https://www.readbyqxmd.com/read/29244129/dolutegravir-reshapes-the-genetic-diversity-of-hiv-1-reservoirs
#1
Pierre Gantner, Guinevere Q Lee, David Rey, Thibault Mesplede, Marialuisa Partisani, Christine Cheneau, Geneviève Beck-Wirth, Jean-Pierre Faller, Mahsa Mohseni-Zadeh, Martin Martinot, Mark A Wainberg, Samira Fafi-Kremer
Objectives: Better understanding of the dynamics of HIV reservoirs under ART is a critical step to achieve a functional HIV cure. Our objective was to assess the genetic diversity of archived HIV-1 DNA over 48 weeks in blood cells of individuals starting treatment with a dolutegravir-based regimen. Methods: Eighty blood samples were prospectively and longitudinally collected from 20 individuals (NCT02557997) including: acutely (n = 5) and chronically (n = 5) infected treatment-naive individuals, as well as treatment-experienced individuals who switched to a dolutegravir-based regimen and were either virologically suppressed (n = 5) or had experienced treatment failure (n = 5)...
December 13, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29244118/lower-dolutegravir-plasma-concentrations-in-hiv-positive-patients-receiving-valproic-acid
#2
Annagloria Palazzo, Mattia Trunfio, Veronica Pirriatore, Maurizio Milesi, Amedeo De Nicolò, Chiara Alcantarini, Antonio D'Avolio, Stefano Bonora, Giovanni Di Perri, Andrea Calcagno
No abstract text is available yet for this article.
December 12, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29239896/ex-vivo-antiretroviral-potency-of-newer-integrase-strand-transfer-inhibitors-cabotegravir-and-bictegravir-in-hiv-1-non-b-subtypes
#3
Ujjwal Neogi, Kamlendra Singh, Shambhu G Aralaguppe, Leonard C Rogers, Duncan T Njenda, Stefan G Sarafianos, Bo Hejdeman, Anders Sönnerborg
OBJECTIVE: To determine the antiretroviral activity of the integrase strand transfer inhibitors (INSTIs), raltegravir, elvitegravir, dolutegravir, cabotegravir and bictegravir, against different subtypes as well as primary and acquired drug resistance mutations (DRM) in a patient-cohort infected with diverse subtypes. DESIGN: Biochemical and virological drug sensitivity analysis using patient derived HIV-1 genes and cross-sectional/longitudinal clinical study. METHODS: Assays for inhibition of 3'-end processing (IC50-3P), strand transfer (IC50-ST) and drug sensitivity (DSA) for five INSTIs were done using patient-derived integrase or gag-pol genes from subtypes A1, B, C, 01_AE and 02_AG...
December 12, 2017: AIDS
https://www.readbyqxmd.com/read/29239893/switch-from-tenofovir-disoproxil-fumarate-combination-to-dolutegravir-plus-rilpivirine-improves-parameters-of-bone-health
#4
Grace A Mccomsey, Sergio Lupo, David Parks, Mónica Coronado Poggio, Joseph De Wet, Lesley P Kahl, Kostas Angelis, Brian Wynne, Kati Vandermeulen, Martin Gartland, Michael Cupo, Michael Aboud
OBJECTIVE: Bone mineral density (BMD) loss, a risk factor for osteoporosis, has been attributed to HIV infection and antiretroviral therapy (ART), including regimens containing tenofovir disoproxil fumarate. DESIGN: Study 202094 is an open-label, parallel-group, sub-study of the phase III SWORD-1 and SWORD-2 studies (ClincialTrials.gov identifier, NCT02478632). METHODS: HIV-1-infected adults with HIV-1 RNA < 50 copies per mL who received ART containing tenofovir disoproxil fumarate for ≥6 months were randomized to receive dolutegravir+rilpivirine or continue current ART regimen...
December 12, 2017: AIDS
https://www.readbyqxmd.com/read/29206999/expansion-of-viral-load-testing-and-the-potential-impact-on-hiv-drug-resistance
#5
Elliot Raizes, Shannon Hader, Deborah Birx
The US President's Emergency Plan for AIDS Relief (PEPFAR) supports aggressive scale-up of antiretroviral therapy (ART) in high-burden countries and across all genders and populations at risk toward global human immunodeficiency virus (HIV) epidemic control. PEPFAR recognizes the risk of HIV drug resistance (HIVDR) as a consequence of aggressive ART scale-up and is actively promoting 3 key steps to mitigate the impact of HIVDR: (1) routine access to routine viral load monitoring in all settings; (2) optimization of ART regimens; and (3) routine collection and analysis of HIVDR data to monitor the success of mitigation strategies...
December 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29199485/a-safety-evaluation-of-raltegravir-for-the-treatment-of-hiv
#6
Rosa de Miguel, Rocio Montejano, Natalia Stella-Ascariz, Jose R Arribas
Raltegravir (RAL) was the first commercialized agent from a new drug class with an innovative target, the integrase. Since its introduction in clinical practice RAL has become widely used for the treatment of HIV-1 infected patients. A decade after its approval, this article reviews key evidence from RAL with a special interest on safety outcomes. Areas covered: Pharmacologic, safety and efficacy data of RAL from clinical trials and post-commercialization published reports are hereby summarized after a literature review including PubMed search, relating proceedings and abstracts from relevant international HIV conferences, assessment reports from European and United States regulatory agencies and treatment guidelines (World Health Organization, United States Department of Health and Human Services and European AIDS Clinical Society), up to October 2017...
December 2, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29183782/impact-of-dolutegravir-and-efavirenz-on-immune-recovery-markers-results-from-a-randomized-clinical-trial
#7
Jose-Ramon Blanco, Belen Alejos, Santiago Moreno
OBJECTIVE: CD4/CD8 ratio and CD4+ T-cell percentage (CD4%) predicts the risk of AIDS and non-AIDS events. Multiple T-cell marker recovery (MTMR) has been proposed as the most complete level of immune reconstitution. In this study we quantified differences in the CD4/CD8 ratio, CD4% recovery and MTMR after starting HIV-1 treatment with DTG/ABC/3TC vs. EFV/TDF/FTC. METHODS: Exploratory post-hoc analysis of the SINGLE study, a randomized double-blind, clinical trial...
November 25, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29174085/resistance-to-first-line-art-and-a-role-for-dolutegravir
#8
Richard Kaplan, Robin Wood
No abstract text is available yet for this article.
November 22, 2017: Lancet HIV
https://www.readbyqxmd.com/read/29174084/cost-effectiveness-of-public-health-policy-options-in-the-presence-of-pretreatment-nnrti-drug-resistance-in-sub-saharan-africa-a-modelling-study
#9
Andrew N Phillips, Valentina Cambiano, Fumiyo Nakagawa, Paul Revill, Michael R Jordan, Timothy B Hallett, Meg Doherty, Andrea De Luca, Jens D Lundgren, Mutsa Mhangara, Tsitsi Apollo, John Mellors, Brooke Nichols, Urvi Parikh, Deenan Pillay, Tobias Rinke de Wit, Kim Sigaloff, Diane Havlir, Daniel R Kuritzkes, Anton Pozniak, David van de Vijver, Marco Vitoria, Mark A Wainberg, Elliot Raizes, Silvia Bertagnolio
BACKGROUND: There is concern over increasing prevalence of non-nucleoside reverse-transcriptase inhibitor (NNRTI) resistance in people initiating antiretroviral therapy (ART) in low-income and middle-income countries. We assessed the effectiveness and cost-effectiveness of alternative public health responses in countries in sub-Saharan Africa where the prevalence of pretreatment drug resistance to NNRTIs is high. METHODS: The HIV Synthesis Model is an individual-based simulation model of sexual HIV transmission, progression, and the effect of ART in adults, which is based on extensive published data sources and considers specific drugs and resistance mutations...
November 22, 2017: Lancet HIV
https://www.readbyqxmd.com/read/29173177/integrase-strand-transfer-inhibitors-and-the-emergence-of-immune-reconstitution-inflammatory-syndrome-iris
#10
Mina Psichogiou, Dimitrios Basoulis, Maria Tsikala-Vafea, Stefanos Vlachos, Christos J Kapelios, Georgios L Daikos
BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) is a major concern when starting highly active anti-retroviral therapy (HAART) in new patients and especially late presenters. This study attempts to identify risk factors for IRIS and investigate whether certain treatment regimens increase the probability of IRIS for patients at risk. METHODS: Retrospective single-centre study of HIV patients treated with HAART. RESULTS: A total of 417 patients were included...
November 22, 2017: Current HIV Research
https://www.readbyqxmd.com/read/29150412/clinical-benefits-of-using-inulin-clearance-and-cystatin-c-for-determining-glomerular-filtration-rate-in-hiv-1-infected-individuals-treated-with-dolutegravir
#11
Satomi Yukawa, Dai Watanabe, Tomoko Uehira, Takuma Shirasaka
INTRODUCTION: Dolutegravir may inhibit creatinine transporters in renal tubules and elevate serum creatinine levels. We investigated the usefulness of glomerular filtration rate (GFR) measured using inulin clearance (Cin), creatinine clearance (Ccr), and estimated GFR based on both serum creatinine (eGFRcre) and serum cystatin C (eGFRcys). PATIENTS & METHODS: HIV-1-infected Japanese patients with suppressed viremia and whose antiretroviral drug was switched to dolutegravir from other drugs were included (n = 108, Study 1)...
November 14, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/29145807/durability-of-switch-regimens-based-on-rilpivirine-or-on-integrase-inhibitors-both-in-association-with-tenofovir-and-emtricitabine-in-hiv-infected-virologically-suppressed-patients
#12
Nicola Gianotti, Andrea Poli, Silvia Nozza, Laura Galli, Nadia Galizzi, Marco Ripa, Marco Merli, Alessia Carbone, Vincenzo Spagnuolo, Adriano Lazzarin, Antonella Castagna
BACKGROUND: Switch strategies based on rilpivirine/tenofovir/emtricitabine or on an integrase inhibitor (InSTI) plus tenofovir/emtricitabine have never been compared in randomized clinical trials. The main aim of the study was to investigate the durability of these two switch regimens in virologically suppressed, HIV-infected patients. METHODS: Retrospective analysis of patients who started rilpivirine or an InSTI (both with tenofovir and emtricitabine) with <50 HIV-RNA copies/mL and had at least one HIV-RNA assessed while receiving the study regimen...
November 16, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29112070/switching-from-a-ritonavir-boosted-protease-inhibitor-to-a-dolutegravir-based-regimen-for-maintenance-of-hiv-viral-suppression-in-patients-with-high-cardiovascular-risk
#13
José M Gatell, Lambert Assoumou, Graeme Moyle, Laura Waters, Margaret Johnson, Pere Domingo, Julie Fox, Esteban Martinez, Hans-Jürgen Stellbrink, Giovanni Guaraldi, Mar Masia, Mark Gompels, Stephane De Wit, Eric Florence, Stefan Esser, François Raffi, Anton L Pozniak
OBJECTIVE: To compare the efficacy, safety, and impact on lipid fractions of switching from a ritonavir-boosted protease inhibitor (PI/r) to a dolutegravir (DTG) regimen. METHODS: HIV type 1-infected adults more than 50 years or with a Framingham score more than 10% were eligible if plasma HIV RNA less than 50 copies per ml for at least 24 weeks while on a PI/r regimen. Patients were randomized to switch to DTG or to remain on PI/r. Primary endpoints were: proportion maintaining HIV RNA less than 50 copies per ml and percentage change from baseline of total cholesterol at week 48...
November 28, 2017: AIDS
https://www.readbyqxmd.com/read/29107563/dolutegravir-monotherapy-as-maintenance-art-bites-the-dust
#14
Janine M Trevillyan, Jennifer F Hoy
No abstract text is available yet for this article.
October 26, 2017: Lancet HIV
https://www.readbyqxmd.com/read/29107562/dolutegravir-as-maintenance-monotherapy-for-hiv-domono-a-phase-2-randomised-non-inferiority-trial
#15
Ingeborg Wijting, Casper Rokx, Charles Boucher, Jeroen van Kampen, Suzan Pas, Theodora de Vries-Sluijs, Carolina Schurink, Hannelore Bax, Maarten Derksen, Eleni-Rosalina Andrinopoulou, Marchina van der Ende, Eric van Gorp, Jan Nouwen, Annelies Verbon, Wouter Bierman, Bart Rijnders
BACKGROUND: The high genetic barrier to resistance of dolutegravir might allow for its use as maintenance monotherapy in patients with HIV. We investigated whether dolutegravir monotherapy was non-inferior to combination antiretroviral therapy (ART) for maintaining virological suppression in patients with HIV-1 infection successfully treated with combination ART. METHODS: We did this open-label, phase 2, randomised non-inferiority trial at two medical centres in the Netherlands...
October 26, 2017: Lancet HIV
https://www.readbyqxmd.com/read/29105160/strength-in-amalgamation-newer-combination-agents-for-hiv-and-implications-for-practice
#16
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/29091219/dolutegravir-plus-abacavir-lamivudine-works-in-adolescents-but-size-matters
#17
Ferran Bossacoma Busquets, Antoni Noguera-Julian, Emilia Sanchez, Claudia Fortuny
No abstract text is available yet for this article.
October 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29091218/hiv-1-dna-ultra-deep-sequencing-analysis-at-initiation-of-the-dual-therapy-dolutegravir%C3%A2-%C3%A2-lamivudine-in-the-maintenance-dolulam-pilot-study
#18
Charlotte Charpentier, Brigitte Montes, Marine Perrier, Nadia Meftah, Jacques Reynes
Background: The DOLULAM study assessed the efficacy of dolutegravir + lamivudine dual therapy to maintain virological suppression in heavily treatment-experienced HIV-1-infected adults. No virological failure occurred during the first year of the dual therapy. Objectives: A virological substudy was conducted to assess the prevalence of M184I/V mutations at dual therapy initiation using historical DNA/RNA genotypes and baseline DNA genotype obtained by next-generation sequencing (NGS)...
October 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29082041/ritonavir-boosted-darunavir-plus-two-nucleoside-reverse-transcriptase-inhibitors-versus-other-regimens-for-initial-antiretroviral-therapy-for-people-with-hiv-infection-a-systematic-review
#19
REVIEW
Tatevik Balayan, Hacsi Horvath, George W Rutherford
BACKGROUND: Darunavir is a second-generation protease-inhibitor used with ritonavir (DRV/r) and two nucleoside reverse-transcriptase inhibitors as an option in first-line antiretroviral treatment (ART). METHODS: We systematically reviewed randomized controlled trials (RCTs) of DRV/r versus other regimens in patients initiating ART. We searched five bibliographic databases and other key resources. We had no language limitations. We assessed bias risk with the Cochrane tool and used GRADE to assess evidence quality...
2017: AIDS Research and Treatment
https://www.readbyqxmd.com/read/29077927/long-term-efficacy-of-dolutegravir-in-treatment-experienced-subjects-failing-therapy-with-hiv-1-integrase-strand-inhibitor-resistant-virus
#20
Antonella Castagna, Micol Ferrara, Laura Galli, Laura Comi, Gaetana Sterrantino, Giovanni Cenderello, Mauro Zaccarelli, Emanuele Focà, Andrea Roncadori, Adriano Lazzarin
Objectives: This study evaluated the virological efficacy of dolutegravir 50 mg twice daily in 190 HIV-1 failing antiretroviral-experienced patients with previous exposure to first-generation integrase strand transfer inhibitor (INSTI) over a 5 year follow-up using data from clinical practice. Patients and methods: This analysis included HIV-1-infected patients who were ≥18 years of age, treatment experienced, had HIV-1 RNA >50 copies/mL, with INSTI-resistant virus, who started dolutegravir 50 mg twice daily plus optimized background therapy (OBT), recorded in the national prospective database PRESTIGIO (www...
October 24, 2017: Journal of Antimicrobial Chemotherapy
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