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https://www.readbyqxmd.com/read/28538284/the-advance-study-a-groundbreaking-trial-to-evaluate-a-candidate-universal-antiretroviral-regimen
#1
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...
May 19, 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
#2
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
#3
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
#4
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...
May 16, 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
#5
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
#6
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
#7
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
#8
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...
April 19, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28410249/when-could-new-antiretrovirals-be-recommended-for-national-treatment-programmes-in-low-income-and-middle-income-countries-results-of-a-who-think-tank
#9
Marco Vitoria, Nathan Ford, Polly Clayden, Anton L Pozniak, Andrew M Hill
PURPOSE OF REVIEW: To discuss barriers and opportunities for the introduction of new antiretrovirals into national treatment programmes in low-income and middle-income countries to support further treatment scale-up. Invitees to a WHO Think Tank in February 2017 evaluated recently published results. RECENT FINDINGS: There is not sufficient clinical experience of dolutegravir (DTG), tenofovir alafenamide (TAF) or efavirenz 400 mg (EFV400) to recommend their use in pregnancy...
April 12, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28403692/severe-hypokalemia-due-to-a-possible-drug-drug-interaction-between-vinblastine-and-antiretrovirals-in-a-hiv-infected-patient-with-hodgkin-s-lymphoma
#10
Ezequiel Cordova, Laura Morganti, Andrea Odzak, Florencia Arcondo, Mariana Silva, Marcelo Zylberman, Claudia Rodriguez
A 60-year-old HIV-1 infected woman on antiretroviral therapy (emtricitabine/tenofovir, and ritonavir-boosted atazanavir) developed Hodgkin's lymphoma. The patient initiated ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) chemotherapy and presented with neutropenia and severe hypokalemia. Hypokalemia was considered as part of a proximal tubular renal dysfunction, and other causes of hypokalemia were excluded. Due to suspicion of drug--drug interactions between antiretrovirals and vinblastine, ritonavir-boosted atazanavir was switched to dolutegravir and the patient continued emtricitabine/tenofovir...
January 1, 2017: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/28403028/compatibility-of-next-generation-first-line-antiretrovirals-with-rifampicin-based-antituberculosis-therapy-in-resource-limited-settings
#11
Gary Maartens, Marta Boffito, Charles Flexner
PURPOSE OF REVIEW: Reduced dose efavirenz, dolutegravir, and/or tenofovir alafenamide (TAF) are likely to be used in the next generation of first-line antiretroviral therapy in resource limited settings, where HIV-associated tuberculosis is common. Rifampicin, which is a key component of first-line antituberculosis therapy, is a potent inducer of many drug transporters and metabolising enzymes. We reviewed the literature for potential or actual drug--drug interactions between these antiretrovirals and rifampicin...
April 11, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28401876/dolutegravir-abacavir-lamivudine-versus-current-art-in-virally-suppressed-patients-striiving-a-48-week-randomized-non-inferiority-open-label-phase-iiib-study
#12
Benoît Trottier, Jordan E Lake, Ken Logue, Cynthia Brinson, Lizette Santiago, Clare Brennan, Justin A Koteff, Brian Wynne, Judy Hopking, Catherine Granier, Michael Aboud
BACKGROUND: Simplified dosing regimens are important for patients who face challenges in adhering to HIV-1 therapy. We investigated the safety and virologic efficacy of switching to once-daily abacavir/dolutegravir/lamivudine (ABC/DTG/3TC). METHODS: The STRIIVING study was a randomized, open-label, phase IIIb study in adults with HIV-1 RNA <50 copies/mL on antiretroviral therapy (ART) at enrolment (ClinicalTrials.gov identifier, NCT02105987). Subjects were randomly assigned to switch to ABC/DTG/3TC once daily for 48 weeks (early-switch group) or continue current ART for 24 weeks and then switch to ABC/DTG/3TC (late-switch group)...
April 12, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28400541/correction-salvage-therapy-or-simplification-of-salvage-regimens-with-dolutegravir-plus-ritonavir-boosted-darunavir-dual-therapy-in-highly-cart-experienced-subjects-an-italian-cohort
#13
Amedeo F Capetti, Gaetana Sterrantino, Maria V Cossu, Giovanni Cenderello, Anna M Cattelan, Giuseppe V De Socio, Stefano Rusconi, Niccolò Riccardi, Gian M Baldin, Serena Cima, Fosca P Niero, Giuliano Rizzardini, Lolita Sasset
No abstract text is available yet for this article.
November 28, 2016: Antiviral Therapy
https://www.readbyqxmd.com/read/28397245/interactions-between-integrase-inhibitors-and-human-arginase-1
#14
Lucia Lisi, Michela Pizzoferrato, Fabiola Teresa Miscioscia, Alessandra Topai, Pierluigi Navarra
The neuro-pathogenic mechanism(s) underlying HIV-associated neurocognitive disorders are mostly unknown. HIV-infected macrophages and microglial cells play a crucial role and the metabolic fate of l-arginine may be highly relevant to microglia activation. In this context, arginase (ARG), which uses l-arginine as substrate, can be on the same time a target and source of oxidative stress and inflammation. In this study, we investigated whether integrase strand transfer inhibitors share with the other antiretroviral drugs the ability to inhibit ARG activity...
April 11, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28389458/probable-interaction-between-levothyroxine-and-ritonavir-case-report-and-literature-review
#15
Rahul Sahajpal, Rabia A Ahmed, Christine A Hughes, Michelle M Foisy
PURPOSE: A case of probable interaction of levothyroxine and ritonavir is presented along with a review of the relevant literature and recommendations on clinical management. SUMMARY: A 37-year-old woman with human immunodeficiency virus infection who had recently undergone thyroidectomy for a benign multinodular goiter presented to a clinic with hypothyroidism (she was also found to be pregnant), and treatment with levothyroxine 75 μg daily was initiated. While receiving antiretroviral therapy (abacavir-lamivudine and lopinavir-ritonavir) during pregnancy, the patient had persistently elevated serum thyroid-stimulating hormone (TSH) concentrations (up to 125...
April 15, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28387810/dolutegravir-monotherapy-in-hiv-infected-naive-patients-with-an-hiv-rna-load-100%C3%A2-000-copies-ml-a-medium-term-follow-up
#16
Massimiliano Lanzafame, Stefano Nicolè, Davide Gibellini, Emanuela Lattuada, Giulia Cucchetto, Fabio Rigo, Erica Diani, Ercole Concia, Sandro Vento
No abstract text is available yet for this article.
April 6, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28383299/a-cost-savings-analysis-of-a-candidate-universal-antiretroviral-regimen
#17
David Ripin, Vineet R Prabhu
PURPOSE OF REVIEW: Despite significant strides in tackling HIV/AIDS in low-income and middle-income countries (LMICs), many treatment shortcomings remain, with limited drug selection to patients emerging as a critical challenge. The potential cost-savings benefits of adopting newer drugs as near-universal first-line antiretroviral (ARV) regimens that also provide improved clinical outcomes are discussed. RECENT FINDINGS: In the near term, a fixed-dose combination of dolutegravir (DTG or D) with tenofovir disoproxil fumarate (TDF), and either lamivudine or emtricitabine (XTC), that is, tenofovir disoproxil fumarate/XTC/DTG (TXD) (X = XTC), could represent a near-universal first-line antiretroviral regimen offering significant clinical benefit, commodity savings, and overall health system savings...
April 5, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28377526/the-r263k-dolutegravir-resistance-associated-substitution-progressively-decreases-hiv-1-integration
#18
Thibault Mesplède, Jing Leng, Hanh Thi Pham, Jiaming Liang, Yudong Quan, Yingshan Han, Mark A Wainberg
Human immunodeficiency virus (HIV) infection persists despite decades of active antiretroviral therapy (ART), effectively preventing viral eradication. Treatment decreases plasma viral RNA, but viral DNA persists, mostly integrated within the genome of nucleated blood cells. Viral DNA blood levels correlate with comorbidities and the rapidity of viral rebound following treatment interruption. To date, no intervention aiming at decreasing HIV DNA levels below those attained through ART has been successful. This includes use of some integrase inhibitors either as part of ART or in treatment intensification studies...
April 4, 2017: MBio
https://www.readbyqxmd.com/read/28375875/emergent-drug-resistance-with-integrase-strand-transfer-inhibitor-based-regimens-incidence-and-risk-factors
#19
Katherine J Lepik, P Richard Harrigan, Benita Yip, Lu Wang, Marjorie A Robbins, Wendy W Zhang, Junine Toy, Linda Akagi, Viviane Dias Lima, Silvia Guillemi, Julio S G Montaner, Rolando Barrios
OBJECTIVES: To estimate the incidence of and risk factors for emergent resistance to integrase inhibitors (INSTI) and nucleoside(-tide) reverse transcriptase inhibitors (NRTI) in HIV-1-infected adults receiving an INSTI plus two NRTIs. DESIGN: Retrospective cohort study. METHODS: Persons ≥19 years were included if they received their first prescription for raltegravir, elvitegravir or dolutegravir in British Columbia, Canada in 2012-2014, and were followed to 31-Dec-2015...
April 3, 2017: AIDS
https://www.readbyqxmd.com/read/28369593/drug-resistance-mutations-in-hiv-2-patients-failing-raltegravir-and-influence-on-dolutegravir-response
#20
Silvia Requena, Ana Treviño, Teresa Cabezas, Rosa Garcia-Delgado, María José Amengual, Ana Belén Lozano, María Peñaranda, Juan Manuel Fernández, Vicente Soriano, Carmen de Mendoza
Background: A broader extent of amino acid substitutions in the integrase of HIV-2 compared with HIV-1 might enable greater cross-resistance between raltegravir and dolutegravir in HIV-2 infection. Few studies have examined the virological response to dolutegravir in HIV-2 patients that failed raltegravir. Methods: All patients recorded in the HIV-2 Spanish cohort were examined. The integrase coding region was sequenced in viraemic patients. Changes associated with resistance to raltegravir and dolutegravir in HIV-1 were recorded...
March 23, 2017: Journal of Antimicrobial Chemotherapy
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