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Dolutegravir

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https://www.readbyqxmd.com/read/28637235/monotherapy-with-either-dolutegravir-or-raltegravir-fails-to-durably-suppress-hiv-viraemia-in-humanized-mice
#1
Alonso Heredia, Said Hassounah, Sandra Medina-Moreno, Juan C Zapata, Nhut M Le, Yingshan Han, James S Foulke, Charles Davis, Joseph Bryant, Robert R Redfield, Mark A Wainberg
Objectives: To compare the effectiveness of HIV integrase inhibitor monotherapy between raltegravir and dolutegravir as an approach to simplify therapy. Methods: We evaluated and compared the efficacy of 20 week monotherapy with dolutegravir or raltegravir in humanized mice (HSC-NSG) infected with HIV BaL . Plasma HIV RNA was measured by quantitative RT-PCR (limit of detection of 150 copies/45 μL of plasma) and drug levels by LC-MS/MS. Escape viruses were genotyped and analysed for replication capacity and drug susceptibility in tissue culture...
June 13, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28632474/evaluation-of-the-concurrent-use-of-dolutegravir-and-metformin-in-human-immunodeficiency-virus-infected-patients
#2
Anne Masich, Melissa E Badowski, Michelle D Liedtke, Patricia P Fulco
An analysis of the interaction between dolutegravir and metformin was conducted in the HIV ambulatory clinic setting. This was a multicenter, retrospective case series evaluating adult, HIV-infected patients concurrently prescribed dolutegravir and metformin. Historical electronic medical records were utilized to collect case-specific data. Laboratory parameters including serum creatinine (SCr), hemoglobin A1c (HgbA1c), plasma HIV RNA, CD4 cell count, and lactate were reviewed. Adverse drug reactions were assessed using patient-reported gastrointestinal intolerance and hypoglycemic symptoms...
January 1, 2017: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/28627771/clinical-experience-with-the-integrase-inhibitors-dolutegravir-and-elvitegravir-in-hiv-infected-patients-efficacy-safety-and-tolerance
#3
Purificación Cid-Silva, Josep María Llibre, Noelia Fernández-Bargiela, Luis Margusino-Framiñán, Vanesa Balboa-Barreiro, Berta Pernas-Souto, Isabel Martín-Herranz, Ángeles Castro-Iglesias, Eva Poveda-López
Two integrase inhibitors (INSTIs), Dolutegravir (DTG) and Elvitegravir/Cobicistat (EVG/COBI) have joined recently the pharmacotherapy arsenal against HIV. This study evaluated the efficacy and tolerability of these INSTIs in the last two years. A retrospective observational study in patients who started DTG or EVG/COBI from January 2015 to January 2017 at a reference hospital in Northwestern Spain was done. Epidemiological, clinical and immunovirological data were recorded. A statistical analysis was performed using SPSS software...
June 19, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28621159/dual-antiretroviral-therapy-for-hiv-infection
#4
Vicente Soriano
For two decades' triple combinations of antiretrovirals have been the standard treatment for HIV infection. The challenges of such lifelong therapy include long-term side effects, high costs and reduced drug adherence. The recent advent of more potent and safer antiretrovirals has renewed the interest for simpler HIV regimens. Areas covered: We discuss the pros and cons of dual antiretroviral therapies in both drug-naïve and in treatment-experienced patients with viral suppression (switch strategy). Expert Opinion: Some dual antiretroviral regimens are safe and efficacious, particularly as maintenance therapy...
June 16, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28605418/should-we-be-testing-for-baseline-integrase-resistance-in-patients-newly-diagnosed-with-hiv
#5
Yiannis Koullias, Paul E Sax, Naomi F Fields, Rochelle P Walensky, Emily P Hyle
Background: Current guidelines recommend genotype resistance testing at diagnosis to guide initial selection of antiretroviral therapy (ART). Many standard resistance genotypes exclude testing for resistance to integrase inhibitors ("IR-testing"), although this class of drugs is a component of most recommended first-line regimens. Methods: We compared the 96-week clinical outcomes and cost-effectiveness of two strategies: no IR-testing vs. IR-testing performed at HIV diagnosis...
June 9, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28598790/croi-2017-advances-in-antiretroviral-therapy
#6
Joyce Jones, Barbara S Taylor, Hong-Van Tieu, Timothy J Wilkin
The 2017 Conference on Retroviruses and Opportunistic Infections (CROI) featured exciting preclinical data on investigational antiretroviral agents with good in vitro efficacy and long half-lives. Investigational medications, including bictegravir, demonstrated excellent efficacy and tolerability, as did dual-agent therapy with dolutegravir paired with rilpivirine or with lamivudine. Dolutegravir monotherapy proved inadvisable due to virologic failure and resistance. The gap between high- and low-income settings along the HIV care continuum is narrowing, with Zimbabwe, Malawi, and Zambia approaching the 90-90-90 targets established by the joint United Nations Programme on HIV/AIDS (UNAIDS), whereas communities in the Southern United States are falling behind...
May 2017: Topics in Antiviral Medicine
https://www.readbyqxmd.com/read/28583191/hiv-drug-resistance-against-strand-transfer-integrase-inhibitors
#7
REVIEW
Kaitlin Anstett, Bluma Brenner, Thibault Mesplede, Mark A Wainberg
Integrase strand transfer inhibitors (INSTIs) are the newest class of antiretroviral drugs to be approved for treatment and act by inhibiting the essential HIV protein integrase from inserting the viral DNA genome into the host cell's chromatin. Three drugs of this class are currently approved for use in HIV-positive individuals: raltegravir (RAL), elvitegravir (EVG), and dolutegravir (DTG), while cabotegravir (CAB) and bictegravir (BIC) are currently in clinical trials. RAL and EVG have been successful in clinical settings but have relatively low genetic barriers to resistance...
June 5, 2017: Retrovirology
https://www.readbyqxmd.com/read/28579016/executive-summary-of-the-gesida-national-aids-plan-consensus-document-on-antiretroviral-therapy-in-adults-infected-by-the-human-immunodeficiency-virus-updated-january-2017
#8
(no author information available yet)
Antiretroviral therapy (ART) is recommended for all patients infected by HIV-1. The objective of ART is to achieve an undetectable plasma viral load (PVL). Initial ART should be based on a combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors (tenofovir in either of its two formulations plus emtricitabine or abacavir plus lamivudine) and another drug from a different family. Four of the recommended regimens, all of which have an integrase inhibitor as the third drug (dolutegravir, elvitegravir boosted with cobicistat or raltegravir), are considered preferential, whereas a further 3 regimens (based on elvitegravir/cobicistat, rilpivirine, or darunavir boosted with cobicistat or ritonavir) are considered alternatives...
May 31, 2017: Enfermedades Infecciosas y Microbiología Clínica
https://www.readbyqxmd.com/read/28576126/effective-treatment-of-sivcpz-induced-immunodeficiency-in-a-captive-western-chimpanzee
#9
Hannah J Barbian, Raven Jackson-Jewett, Corrine S Brown, Frederic Bibollet-Ruche, Gerald H Learn, Timothy Decker, Edward F Kreider, Yingying Li, Thomas N Denny, Paul M Sharp, George M Shaw, Jeffrey Lifson, Edward P Acosta, Michael S Saag, Katharine J Bar, Beatrice H Hahn
BACKGROUND: Simian immunodeficiency virus of chimpanzees (SIVcpz), the progenitor of human immunodeficiency virus type 1 (HIV-1), is associated with increased mortality and AIDS-like immunopathology in wild-living chimpanzees (Pan troglodytes). Surprisingly, however, similar findings have not been reported for chimpanzees experimentally infected with SIVcpz in captivity, raising questions about the intrinsic pathogenicity of this lentivirus. FINDINGS: Here, we report progressive immunodeficiency and clinical disease in a captive western chimpanzee (P...
June 2, 2017: Retrovirology
https://www.readbyqxmd.com/read/28574967/dolutegravir-and-weight-gain-an-unexpected-bothering-side-effect
#10
Amélie Menard, Line Meddeb, Herve Tissot-Dupont, Isabelle Ravaux, Catherine Dhiver, Saadia Mokhtari, Christelle Tomei, Philippe Brouqui, Philippe Colson, Andreas Stein
No abstract text is available yet for this article.
June 19, 2017: AIDS
https://www.readbyqxmd.com/read/28570368/prioritizing-the-most-needed-formulations-to-accelerate-paediatric-antiretroviral-therapy-scale-up
#11
Martina Penazzato, Claudia Palladino, Nandita Sugandhi
PURPOSE OF REVIEW: Initiatives are in place to reach super-fast targets by 2018 for paediatric patients living with HIV. However, these efforts are unlikely to be successful until better paediatric antiretrovirals and treatment strategies are available. This commentary reviews the specific features, challenges, and recent developments in paediatric HIV treatment to determine optimal regimen sequencing and use of available drug options. It also outlines a medium and long-term vision for treatment optimization as endorsed by the paediatric antiretroviral drug optimization group...
July 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28556353/decreased-absorption-of-dolutegravir-and-tenofovir-disoproxil-fumarate-but-not-emtricitabine-in-an-hiv-infected-patient-following-oral-and-jejunostomy-tube-administration
#12
Kristina M Brooks, Katy L Garrett, Safia S Kuriakose, Jomy M George, Gayle Balba, Bria Bailey, Megan Anderson, H Clifford Lane, Frank Maldarelli, Alice K Pau
The use of enteral feeding tubes to administer antiretroviral medication administration is necessary in certain patients with human immunodeficiency virus (HIV) infection. However, adequacy of drug exposures after these administration routes are largely unknown, making dosing recommendations and the attainment of viral suppression challenging in this patient population. This report describes a patient with advanced HIV infection and a complicated medical history, including long-term intractable nausea/vomiting necessitating antiretroviral medication administration via a Roux-en-Y jejunostomy (J)-tube...
May 27, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28538284/the-advance-study-a-groundbreaking-trial-to-evaluate-a-candidate-universal-antiretroviral-regimen
#13
Willem D F Venter, Polly Clayden, Celicia Serenata
PURPOSE OF REVIEW: Current WHO-recommended first-line therapy in low-income and middle-income countries has been very successful in saving millions of lives but still has toxicity concerns and a low barrier to resistance. RECENT FINDINGS: Two candidate antiretrovirals may substantially transform first-line therapy in low-income and middle-income countries, yielding a safer, more robust and cheaper regimen. Tenofovir alafenamide carries toxicity and cost benefits over tenofovir disoproxil fumarate...
July 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28537061/dolutegravir-lamivudine-as-initial-therapy-in-hiv-1-infected-arv-naive-patients-48-week-results-of-the-paddle-pilot-antiretroviral-design-with-dolutegravir-lamivudine-study
#14
Pedro Cahn, María José Rolón, María Inés Figueroa, Ana Gun, Patricia Patterson, Omar Sued
INTRODUCTION: A proof-of-concept study was designed to evaluate the antiviral efficacy, safety and tolerability of a two-drug regimen with dolutegravir 50 mg once daily (QD) plus lamivudine 300 mg once daily as initial highly active antiretroviral therapy (HAART) among antiretroviral (ARV)-naive patients. METHODS: PADDLE is a pilot study including 20 treatment-naive adults. To be selected, participants had no IAS-USA-defined resistance, HIV-1 RNA ≤100,000 copies/mL at screening and negative HBsAg...
May 9, 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/28533248/impact-of-hiv-1-integrase-l74f-v75i-mutations-from-a-clinical-isolate-on-resistance-to-second-generation-integrase-strand-transfer-inhibitors
#15
Atsuko Hachiya, Karen A Kirby, Yoko Ido, Urara Shigemi, Masakazu Matsuda, Reiko Okazaki, Junji Imamura, Stefan G Sarafianos, Yoshiyuki Yokomaku, Yasumasa Iwatani
A novel HIV-1 integrase mutation pattern, L74F/V75I, which conferred resistance to first-generation integrase strand transfer inhibitors (INSTIs), was identified in a clinical case with virological failure under a raltegravir-based regimen. Addition of L74F/V75I to N155H or G140S/Q148H increased resistance levels to second-generation INSTIs, dolutegravir (>385-, 100-fold, respectively) and cabotegravir (153-, 197-fold, respectively). These findings are important for developing an accurate interpretation system of INSTI resistance and the rational design of next-generation INSTIs...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28520610/candidates-for-inclusion-in-a-universal-antiretroviral-regimen-dolutegravir
#16
Pedro Cahn
PURPOSE OF REVIEW: The review addresses the role of dolutegravir (DTG) in first-line therapy. In the era of test and treat, where United Nations AIDS Program and WHO have set the ambitious targets of 90/90/90, new efficacious, well tolerated, and simple therapeutic options are needed. RECENT FINDINGS: DTG has been tested in large clinical trials in treatment-naïve patients, showing noninferiority to raltegravir and superiority compared with efavirenz and ritonavir-boosted darunavir, respectively...
July 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28472812/agreement-between-estimated-and-measured-renal-function-in-an-everyday-clinical-outpatient-setting-of-human-immunodeficiency-virus-infected-individuals
#17
Magnus Glindvad Ahlström, Andreas Kjær, Jan Gerstoft, Niels Obel
INTRODUCTION: Estimated renal function (eRF) has been widely implemented as a screening tool in handling human immunodeficiency virus (HIV)-infected individuals. Our primary objective was to investigate the agreement between measured renal function (mRF) and eRF in HIV-infected individuals in an everyday clinical setting. METHODS: A single-center study at the HIV-outpatient clinic at Copenhagen University Hospital, Rigshospitalet. Study period from January 1, 2004-June 1, 2015...
May 5, 2017: Nephron
https://www.readbyqxmd.com/read/28472323/hiv-1-strains-belonging-to-large-phylogenetic-clusters-show-accelerated-escape-from-integrase-inhibitors-in-cell-culture-compared-with-viral-isolates-from-singleton-small-clusters
#18
Bluma G Brenner, Ruxandra-Ilinca Ibanescu, Maureen Oliveira, Michel Roger, Isabelle Hardy, Jean-Pierre Routy, Fred Kyeyune, Miguel E Quiñones-Mateu, Mark A Wainberg
Objectives: Viral phylogenetics revealed two patterns of HIV-1 spread among MSM in Quebec. While most HIV-1 strains ( n  =   2011) were associated with singleton/small clusters (cluster size 1-4), 30 viral lineages formed large networks (cluster size 20-140), contributing to 42% of diagnoses between 2011 and 2015. Herein, tissue culture selections ascertained if large cluster lineages possessed higher replicative fitness than singleton/small cluster isolates, allowing for viral escape from integrase inhibitors...
May 2, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28441180/neuropsychiatric-adverse-effects-on-dolutegravir-an-emerging-concern-in-europe
#19
Amélie Menard, Clementine Montagnac, Caroline Solas, Line Meddeb, Catherine Dhiver, Christelle Tomei, Isabelle Ravaux, Herve Tissot-Dupont, Saadia Mokhtari, Philippe Colson, Andreas Stein
No abstract text is available yet for this article.
May 15, 2017: AIDS
https://www.readbyqxmd.com/read/28426519/toward-a-universal-antiretroviral-regimen-special-considerations-of-pregnancy-and-breast-feeding
#20
Amy L Slogrove, Polly Clayden, Elaine J Abrams
PURPOSE OF REVIEW: As optimized antiretroviral therapy (ART) regimens are prepared for introduction in low-income and middle-income countries (LMIC), we consider the current evidence related to dosing, efficacy and safety during pregnancy and breastfeeding of next-generation first-line and second-line ART regimens proposed for imminent introduction in the global marketplace. RECENT FINDINGS: Pregnancy pharmacokinetic considerations include potentially insufficient efavirenz exposure if dosed at 400 mg/day, the need for twice daily darunavir dosing and the paucity of data related to tenofovir alafenamide and dolutegravir dosing, safety and efficacy...
July 2017: Current Opinion in HIV and AIDS
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