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https://www.readbyqxmd.com/read/28741965/cost-effectiveness-of-dolutegravir-abacavir-lamivudine-in-hiv-1-treatment-na%C3%A3-ve-tn-patients-in-france
#1
Gilles Pialoux, Anne-Geneviève Marcelin, Hélène Cawston, Caroline Guilmet, Laurent Finkielsztejn, Audrey Laurisse, Céline Aubin
OBJECTIVES: To evaluate the cost-effectiveness of an integrase inhibitor (INI), dolutegravir (DTG), in combination with abacavir (ABC)/lamivudine (3TC) in France, in treatment-naïve (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 25, 2017: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/28737946/structure-guided-optimization-of-hiv-integrase-strand-transfer-inhibitors
#2
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 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...
July 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28735382/combined-medication-of-antiretroviral-drugs-tenofovir-disoproxil-fumarate-emtricitabine-and-raltegravir-reduces-neural-progenitor-cell-proliferation-in-vivo-and-in-vitro
#3
Peipei Xu, Yingchun Wang, Zhao Qin, Lisha Qiu, Min Zhang, Yunlong Huang, Jialin C Zheng
The application of combination antiretroviral therapy has greatly reduced the death rate from AIDS. However, up to 50% of patients on combination antiretroviral therapy develop HIV-associated neurocognitive disorders (HAND), which is associated with residual neuroinflammation and oxidative injury in the brain. Neural stem cells (NSCs) and progenitors play a vital role in repairing neuronal injuries. Therefore, we hypothesize that combination antiretroviral therapy may adversely affect NSCs/progenitors, contributing to the increasing prevalence of HAND...
July 22, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28723333/enhanced-prophylaxis-plus-antiretroviral-therapy-for-advanced-hiv-infection-in-africa
#4
James Hakim, Victor Musiime, Alex J Szubert, Jane Mallewa, Abraham Siika, Clara Agutu, Simon Walker, Sarah L Pett, Mutsa Bwakura-Dangarembizi, Abbas Lugemwa, Symon Kaunda, Mercy Karoney, Godfrey Musoro, Sheila Kabahenda, Kusum Nathoo, Kathryn Maitland, Anna Griffiths, Margaret J Thomason, Cissy Kityo, Peter Mugyenyi, Andrew J Prendergast, A Sarah Walker, Diana M Gibb
BACKGROUND: In sub-Saharan Africa, among patients with advanced human immunodeficiency virus (HIV) infection, the rate of death from infection (including tuberculosis and cryptococcus) shortly after the initiation of antiretroviral therapy (ART) is approximately 10%. METHODS: In this factorial open-label trial conducted in Uganda, Zimbabwe, Malawi, and Kenya, we enrolled HIV-infected adults and children 5 years of age or older who had not received previous ART and were starting ART with a CD4+ count of fewer than 100 cells per cubic millimeter...
July 20, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28721059/cost-effectiveness-analysis-of-dolutegravir-plus-backbone-compared-with-raltegravir-plus-backbone-darunavir-ritonavir-plus-backbone-and-efavirenz-tenofovir-emtricitabine-in-treatment-na%C3%A3-ve-and-experienced-hiv-positive-patients
#5
Umberto Restelli, Giuliano Rizzardini, Andrea Antinori, Adriano Lazzarin, Marzia Bonfanti, Paolo Bonfanti, Davide Croce
BACKGROUND: In January 2014, the European Medicines Agency issued a marketing authorization for dolutegravir (DTG), a second-generation integrase strand transfer inhibitor for HIV treatment. The study aimed at determining the incremental cost-effectiveness ratio (ICER) of the use of DTG+backbone compared with raltegravir (RAL)+backbone, darunavir (DRV)+ritonavir(r)+backbone and efavirenz/tenofovir/emtricitabine (EFV/TDF/FTC) in HIV-positive treatment-naïve patients and compared with RAL+backbone in treatment-experienced patients, from the Italian National Health Service's point of view...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28719012/the-impact-of-immunoglobulin-in-acute-hiv-infection-on-the-hiv-reservoir-a-randomized-controlled-trial
#6
J Tiraboschi, S Ray, K Patel, A Teague, M Pace, P Phalora, N Robinson, E Hopkins, J Meyerowitz, Y Wang, J Cason, S Kaye, J Sanderson, P Klenerman, S Fidler, J Frater, J Fox
OBJECTIVES: Antiretroviral therapy (ART) during acute HIV infection (AHI) restricts the HIV reservoir, but additional interventions are necessary to induce a cure. Intravenous immunoglobulin (IVIG) is not HIV-specific but is safe and temporarily reduces the HIV reservoir in chronic HIV infection. We present a randomized controlled trial to investigate whether IVIG plus ART in AHI reduces the HIV reservoir and immune activation compared with ART alone. METHODS: Ten men with AHI (Fiebig II-IV) initiated ART (tenofovir, entricitabine, ritonavir boosted darunavir and raltegravir) at HIV-1 diagnosis and were randomized to ART alone or ART plus 5 days of IVIG, once virally suppressed (week 19)...
July 18, 2017: HIV Medicine
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
#7
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/28692533/adverse-events-of-raltegravir-and-dolutegravir
#8
Luigia Elzi, Stefan Erb, Hansjakob Furrer, Matthias Cavassini, Alexandra Calmy, Pietro Vernazza, Huldrych Günthard, Enos Bernasconi, Manuel Battegay
OBJECTIVE: To compare the frequency and risk factors of toxicity-related treatment discontinuations between raltegravir and dolutegravir. DESIGN: Prospective cohort study. METHODS: All antiretroviral therapy (ART)-naïve and ART-experienced HIV-infected individuals from the Swiss HIV Cohort Study who initiated raltegravir or dolutegravir between 2006 and 2015 were investigated concerning treatment modification within the first year. RESULTS: Of 4041 patients initiating ART containing raltegravir (n = 2091) or dolutegravir (n = 1950), 568 patients discontinued ART during the first year, corresponding to a rate of 15...
August 24, 2017: AIDS
https://www.readbyqxmd.com/read/28683697/assessment-of-off-label-prescribing-profile-evidence-and-evolution
#9
Encarnación Blanco-Reina, Azucena Muñoz-García, Manuel Jesús Cárdenas-Aranzana, Ricardo Ocaña-Riola, José Ramón Del Prado-Llergo
OBJECTIVES: The objectives of the study were to describe the extent and profile of off-label prescriptions, to evaluate the level of evidence supporting these indications, to assess the research activity in these conditions, and to determine to what extent these were authorized as new indications five years after the application. METHODS: A cross-sectional study including all applications conducted in the Hospital Universitario Reina Sofía in Córdoba during 2010...
July 1, 2017: Farmacia Hospitalaria
https://www.readbyqxmd.com/read/28683645/substitution-of-nevirapine-or-raltegravir-for-protease-inhibitor-vs-rosuvastatin-treatment-for-the-management-of-dyslipidaemia-in-hiv-infected-patients-on-stable-antiretroviral-therapy-nevrast-study
#10
Leonardo Calza, Eleonora Magistrelli, Vincenzo Colangeli, Marco Borderi, Linda Bussini, Isabella Bon, Maria Carla Re, Pierluigi Viale
OBJECTIVES: An observational, prospective, cohort study was performed to compare efficacy and safety of a switch from ritonavir-boosted protease inhibitor (PI/r) to nevirapine or raltegravir with that of rosuvastatin addition to current antiretroviral therapy in HIV-infected patients with hyperlipidaemia. METHODS: All HIV-infected patients receiving a stable PI/r-based antiretroviral regimen, with persistently suppressed viremia, naïve to non-nucleoside analogues and to integrase strand transfer inhibitors, with mixed hyperlipidaemia, and who underwent a switch from PI/r to nevirapine (Group A) or raltegravir (Group B) or who started rosuvastatin at 10 mg daily (group C) with unchanged antiretroviral regimen were enrolled into the study...
July 6, 2017: Infectious Diseases
https://www.readbyqxmd.com/read/28678879/treatment-with-integrase-inhibitor-suggests-a-new-interpretation-of-hiv-rna-decay-curves-that-reveals-a-subset-of-cells-with-slow-integration
#11
E Fabian Cardozo, Adriana Andrade, John W Mellors, Daniel R Kuritzkes, Alan S Perelson, Ruy M Ribeiro
The kinetics of HIV-1 decay under treatment depends on the class of antiretrovirals used. Mathematical models are useful to interpret the different profiles, providing quantitative information about the kinetics of virus replication and the cell populations contributing to viral decay. We modeled proviral integration in short- and long-lived infected cells to compare viral kinetics under treatment with and without the integrase inhibitor raltegravir (RAL). We fitted the model to data obtained from participants treated with RAL-containing regimes or with a four-drug regimen of protease and reverse transcriptase inhibitors...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28664942/darunavir-stands-up-as-preferred-hiv-protease-inhibitor
#12
Josep Mallolas
Current antiretroviral therapy reaches and maintains viral suppression over the years in more than 90% of treated HIV-infected individuals. Although integrase inhibitors are the preferred third agent in antiretroviral therapy in the current guidelines, rilpivirine, a non-nucleoside reverse transcrip- tase inhibitor, and darunavir (DRV), a second-generation protease inhibitor, are the preferred third companion to be used along with a backbone of two nucleos(t)ide reverse transcriptase inhibitors as first-line triple HIV combination treatment...
April 2017: AIDS Reviews
https://www.readbyqxmd.com/read/28663779/antiretroviral-therapy-containing-raltegravir-to-prevent-mother-to-child-transmission-of-hiv-in-infected-pregnant-women
#13
Diego M Cecchini, Marina G Martinez, Laura M Morganti, Claudia G Rodriguez
We conducted a retrospective study in a general hospital in Buenos Aires, Argentina (2009-2015) aimed at evaluating outcomes in HIV-infected pregnant women (HIPW), who were prescribed raltegravir (RAL)-containing antiretroviral therapy (ART). A total of 239 HIPW were enrolled in our study; among them 31 received RAL (12.9%) at different clinical stages: i) intensification (INS): addition of RAL to current ART because of detectable antepartum viral load, 13 (41.9%); ii) late presenter (LP): standard ART + RAL as fourth drug, 15 (48...
May 31, 2017: Infectious Disease Reports
https://www.readbyqxmd.com/read/28653971/addition-of-etravirine-does-not-enhance-the-initial-decline-of-hiv-1-rna-in-treatment-experienced-patients-receiving-raltegravir
#14
Philippe Flandre, Anne-Geneviève Marcelin, Vincent Calvez
OBJECTIVE: The importance of an early reduction of HIV-1 RNA as a marker for positive longer term outcome is still under debate. We investigate whether antiretroviral-experienced patients receiving raltegravir plus etravirine have a higher early reduction of HIV-1 RNA compared with patients receiving raltegravir. DESIGN: An observational study of treatment-experienced patients. METHODS: The objective is to investigate 349 patients included in a raltegravir resistance study...
August 1, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28637235/monotherapy-with-either-dolutegravir-or-raltegravir-fails-to-durably-suppress-hiv-viraemia-in-humanized-mice
#15
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/28621159/dual-antiretroviral-therapy-for-hiv-infection
#16
Vicente Soriano, Jose Vicente Fernandez-Montero, Laura Benitez-Gutierrez, Carmen de Mendoza, Ana Arias, Pablo Barreiro, José M Peña, Pablo Labarga
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...
July 11, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28590329/antiretroviral-initiation-is-associated-with-increased-skeletal-muscle-area-and-fat-content
#17
Kristine M Erlandson, Suzanne Fiorillo, Fadzai Masawi, Ann Scherzinger, Grace A McComsey, Jordan E Lake, James H Stein, Judith S Currier, Todd T Brown
OBJECTIVE: A greater burden of physical function impairment occurs in HIV-infected adults; the impact of antiretroviral therapy (ART) initiation on muscle density (less dense = more fat), a measure of muscle quality, is unknown. DESIGN: AIDS Clinical Trials Group Study A5260s, a cardiometabolic substudy of A5257, randomized HIV-infected, ART-naive adults to ritonavir-boosted atazanavir, darunavir, or raltegravir with tenofovir/emtricitabine backbone. Single-slice abdominal computed tomography scans from baseline and week 96 were reanalyzed for total and lean muscle area and density...
August 24, 2017: AIDS
https://www.readbyqxmd.com/read/28583191/hiv-drug-resistance-against-strand-transfer-integrase-inhibitors
#18
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
#19
(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/28569776/hiv-integrase-inhibitor-elvitegravir-impairs-rag-functions-and-inhibits-v-d-j-recombination
#20
Mayilaadumveettil Nishana, Namrata M Nilavar, Rupa Kumari, Monica Pandey, Sathees C Raghavan
Integrase inhibitors are a class of antiretroviral drugs used for the treatment of AIDS that target HIV integrase, an enzyme responsible for integration of viral cDNA into host genome. RAG1, a critical enzyme involved in V(D)J recombination exhibits structural similarity to HIV integrase. We find that two integrase inhibitors, Raltegravir and Elvitegravir, interfered with the physiological functions of RAGs such as binding, cleavage and hairpin formation at the recombination signal sequence (RSS), though the effect of Raltegravir was limited...
June 1, 2017: Cell Death & Disease
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