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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/28210500/drug-release-characteristics-and-tissue-distribution-of-rifapentine-polylactic-acid-sustained-release-microspheres-in-rabbits-after-paravertebral-implantation
#2
Zheng Zhang, Linbo Wu, Haijian Li, Zhicheng Long, Xinghua Song
BACKGROUND: Rates of drug-resistant tuberculosis (TB) and TB associated with human immunodeficiency virus (HIV) infection have increased dramatically, intensifying challenges in TB control. New formulations of TB treatment drugs that control drug release and increase local drug concentrations will have a significant impact on mitigating the toxic side effects and increasing the clinical efficacy of anti-TB drugs. OBJECTIVES: The aim was to observe the sustained release characteristics of rifapentine polylactic acid sustained-release microspheres in vivo and the accumulation of rifapentine in other tissues following paravertebral implantation...
November 2016: Iranian Red Crescent Medical Journal
https://www.readbyqxmd.com/read/28208121/2017-update-of-the-drug-resistance-mutations-in-hiv-1
#3
Annemarie M Wensing, Vincent Calvez, Huldrych F Günthard, Victoria A Johnson, Roger Paredes, Deenan Pillay, Robert W Shafer, Douglas D Richman
The 2017 edition of the IAS-USA drug resistance mutations list updates the figures last published in November 2015. The mutations listed are those that have been identified by specific criteria for evidence and drugs described. The figures are designed to assist practitioners in identifying key mutations associated with resistance to antiretroviral drugs and, therefore, in making clinical decisions regarding antiretroviral therapy.
December 2017: Topics in Antiviral Medicine
https://www.readbyqxmd.com/read/28207500/strategic-use-of-dual-regimens-of-boosted-protease-inhibitors-plus-maraviroc-in-poorly-adherent-subjects-in-view-of-long-acting-drugs-a-retrospective-study
#4
Amedeo Ferdinando Capetti, Mariangela Micale, Laura Carenzi, Fosca Niero, Simona Landonio, Stefania Vimercati, Gianfranco Dedivitiis, Giuliano Rizzardini
In view of the forthcoming long-acting antiretrovirals, measures should be taken to prevent the selection of HIV drug resistance mutations. All subjects who had been switched to boosted protease inhibitors plus maraviroc (bPIs/MVC) with baseline HIV-1 RNA >50 copies/mL between June, 2014, and April, 2015, were retrospectively evaluated. HIV-1 RNA, CD4+ T-cells, serum glucose, creatinine, ALT, and adverse events were controlled every 3 to 4 months. We retrospectively analyzed 44 patients: 18 were taking darunavir/ritonavir (DRV/r) and 26 atazanavir/ritonavir (ATV/r) once daily, plus MVC 300 mg once daily...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28206979/effect-of-gender-and-age-on-the-relative-bioavailability-of-doravirine-results-of-a-phase-i-trial-in-healthy-subjects
#5
Martin O Behm, Ka L Yee, Li Fan, Paul Fackler
BACKGROUND: Doravirine is a potent, once-daily, non-nucleoside reverse transcriptase inhibitor with a distinct resistance profile in Phase 3 development for the treatment of HIV-1. As doravirine may be administered to women and the elderly, we investigated the impact of gender and age in doravirine pharmacokinetics. METHODS: In this Phase 1, open-label, single-period, parallel-group investigation, doravirine 100 mg was administered to 36 healthy subjects in 3 groups: elderly men (n=12, 65-80 years), elderly women (n=12, 65-80 years), and young women (n=12, 18-50 years)...
February 16, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28202766/inhibition-of-hiv-1-maturation-via-small-molecule-targeting-of-the-amino-terminal-domain-in-the-viral-capsid-protein
#6
Weifeng Wang, Jing Zhou, Upul D Halambage, Kellie A Jurado, Augusta V Jamin, Yujie Wang, Alan N Engelman, Christopher Aiken
The HIV-1 capsid protein is an attractive therapeutic target owing to its multifunctionality in virus replication and the high fitness cost of amino acid substitutions in capsid to HIV-1 infectivity. To date, small molecule inhibitors have been identified that inhibit HIV-1 capsid assembly and/or impair its function in target cells. Here we describe the mechanism of action of the previously reported capsid-targeting HIV-1 inhibitor, BI compound 1 (C1). We show that C1 acts during HIV-1 maturation to prevent assembly of a mature viral capsid...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28202762/maternal-binding-and-neutralizing-igg-responses-targeting-the-c-terminal-region-of-the-v3-loop-are-predictive-of-reduced-peripartum-hiv-1-transmission-risk
#7
David R Martinez, Nathan Vandergrift, Ayooluwa O Douglas, Erin McGuire, John Bainbridge, Nathan I Nicely, David C Montefiori, Georgia D Tomaras, Genevieve G Fouda, Sallie R Permar
The development of an effective maternal HIV-1 vaccine that could synergize with antiretroviral therapy (ART) to eliminate pediatric HIV-1 infection will require the characterization of maternal immune responses capable of blocking transmission of autologous HIV viruses to the infant. We previously identified that maternal plasma antibody binding to linear epitopes within the variable loop 3 (V3) region of HIV envelope (Env) and neutralizing responses against easy to neutralize tier 1 viruses were associated with reduced risk of peripartum HIV infection in the historic U...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28202091/isolation-unit-for-multidrug-resistant-tuberculosis-patients-in-a-low-endemic-country-a-step-towards-the-world-health-organization-end-tb-strategy
#8
M C Payen, J P VAN Vooren, O Vandenberg, N Clumeck, S DE Wit
Tuberculosis (TB) remains a threat to public health and is the second cause of death due to a single infectious agent after HIV/AIDS. The worldwide distribution of TB is heterogeneous. The incidence is decreasing in most high-income regions, but the situation remains worrying in many parts of the world. The emergence of Mycobacterium tuberculosis strains resistant to key agents used in treatment (rifampin and isoniazid) contributes to TB transmission around the world. To achieve TB elimination, both high and low endemic countries must upscale their efforts to decrease disease transmission and improve cure rates...
February 16, 2017: Epidemiology and Infection
https://www.readbyqxmd.com/read/28198788/high-rates-of-baseline-drug-resistance-and-virologic-failure-among-art-na%C3%A3-ve-hiv-infected-children-in-mali
#9
Claudia S Crowell, Almoustapha I Maiga, Mariam Sylla, Babafemi Taiwo, Niaboula Kone, Assaf P Oron, Robert L Murphy, Anne-Geneviève Marcelin, Ban Traore, Djeneba B Fofana, Gilles Peytavin, Ellen G Chadwick
BACKGROUND: Limited data exist on drug resistance and antiretroviral treatment (ART) outcomes in HIV-1 infected children in West Africa. We determined the prevalence of baseline resistance and correlates of virologic failure (VF) in a cohort of ART naïve HIV-1 infected children <10 years of age initiating ART in Mali. METHODS: Reverse transcriptase and protease genes were sequenced at baseline (before ART) and at 6 months. Resistance was defined according to the Stanford HIV Genotypic Resistance database...
February 13, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28198351/therapeutic-drug-monitoring-guided-raltegravir-dosing-for-prevention-of-vertical-transmission-in-a-premature-neonate-born-to-a-woman-living-with-perinatally-acquired-hiv
#10
Denise Kreutzwiser, Nancy Sheehan, Natalie Dayneka, Benoît Lemire, Alison Wong, Lindy Samson, Jason Brophy
We report a case of therapeutic drug monitoring guided raltegravir use for the prevention of vertical HIV transmission in a premature neonate born to a woman living with perinatally acquired HIV and documented resistance to multiple HIV drugs. Maternal viral load was above 1,000 copies/mL at delivery. This case demonstrates delayed raltegravir elimination in a neonate born at 33 weeks gestational age and a need for less frequent raltegravir dosing than is used in older infants and children.
February 15, 2017: Antiviral Therapy
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
#11
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/28196511/antiretroviral-therapy-related-adverse-effects-can-sub-saharan-africa-cope-with-the-new-test-and-treat-policy-of-the-world-health-organization
#12
Jobert Richie N Nansseu, Jean Joel R Bigna
BACKGROUND: Recent studies have shown that early antiretroviral therapy (ART) initiation results in significant HIV transmission reduction. This is the rationale behind the "test and treat" policy of the World Health Organization (WHO). Implementation of this policy will lead to an increased incidence of ART-related adverse effects, especially in sub-Saharan Africa (SSA). Is the region yet ready to cope with such a challenging issue? MAIN BODY: The introduction and widespread use of ART have drastically changed the natural history of HIV/AIDS, but exposure to ART leads to serious medication-related adverse effects mainly explained by mitochondrial toxicities, and the situation will get worse in the near future...
February 15, 2017: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/28195728/room-temperature-neutron-crystallography-of-drug-resistant-hiv-1-protease-uncovers-limitations-of-x-ray-structural-analysis-at-100k
#13
Oksana O Gerlits, David A Keen, Matthew P Blakeley, John M Louis, Irene T Weber, Andrey Y Kovalevsky
HIV-1 protease inhibitors are crucial for treatment of HIV-1/AIDS, but their effectiveness is thwarted by rapid emergence of drug resistance. To better understand binding of clinical inhibitors to resistant HIV-1 protease, we used room-temperature joint X-ray/Neutron (XN) crystallography to obtain an atomic-resolution structure of the protease triple mutant (V32I/I47V/V82I) in complex with amprenavir. The XN structure reveals a D+ ion located midway between the inner Oδ1 oxygen atoms of the catalytic aspartic acid residues...
February 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28191538/lipodystrophy-hiv-related-and-fgf21-a-new-marker-to-follow-the-progression-of-lipodystrophy
#14
Stefano Benedini, Livio Luzi
Recently new evidence about fibroblast growth factor 21 (FGF21) highlights the opportunities to use this molecule in new pharmaceutical formulations to combat type 2 diabetes and metabolic syndrome. It is well known that HIV is per se a condition of insulin resistance and in particular the patient with HIV-related lipodystrophy has a condition strictly related to metabolic syndrome. Lipodystrophy is associated with severe metabolic side effects, including dyslipidemia, hepatic insulin resistance, and lipid oxidation impairment...
December 1, 2016: Journal of Translational Internal Medicine
https://www.readbyqxmd.com/read/28188461/physical-activity-is-associated-with-metabolic-health-in-men-living-with-hiv
#15
Cuisle Forde, Aisling Loy, Siobhan O'Dea, Fiona Mulcahy, John Gormley, Caroline Daly
Metabolic health is a cause for concern among those living with HIV, especially those on antiretroviral therapy. Physical activity (PA) is known to benefit metabolic health, however, few studies have objectively measured PA or investigated the relationship between PA and metabolic health among those living with HIV. In this study, PA and indices of metabolic health among twenty men living with HIV and twenty age matched HIV-negative men were measured. PA was measured using Actigraph accelerometers. Components of the metabolic syndrome and insulin resistance were measured using routine laboratory methods...
February 10, 2017: AIDS and Behavior
https://www.readbyqxmd.com/read/28188180/a-population-genomics-approach-to-assessing-the-genetic-basis-of-within-host-microevolution-underlying-recurrent-cryptococcal-meningitis-infection
#16
Johanna Rhodes, Mathew A Beale, Mathieu Vanhove, Joseph N Jarvis, Shichina Kannambath, John A Simpson, Anthea Ryan, Graeme Meintjes, Thomas S Harrison, Matthew C Fisher, Tihana Bicanic
Recurrence of meningitis due to Cryptococcus neoformans after treatment causes substantial mortality in HIV/AIDS patients across sub-Saharan Africa. In order to determine whether recurrence occurred due to relapse of the original infecting isolate or reinfection with a different isolate weeks or months after initial treatment, we used whole-genome sequencing to assess the genetic basis of infection in 17 HIV-infected individuals with recurrent cryptococcal meningitis. Comparisons revealed a clonal relationship for 15 pairs of isolates recovered before and after recurrence showing relapse of the original infection...
February 10, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28187212/an-analysis-of-drug-resistance-among-people-living-with-hiv-aids-in-shanghai-china
#17
Fengdi Zhang, Li Liu, Meiyan Sun, Jianjun Sun, Hongzhou Lu
BACKGROUND: Understanding the mechanisms of drug resistance can facilitate better management of antiretroviral therapy, helping to prevent transmission and decrease the morbidity and mortality of people living with HIV/AIDS. However, there is little data about transmitted drug resistance and acquired drug resistance for HIV/AIDS patients in Shanghai. METHODS: A retrospective cohort study of HIV-infected patients who visited the Department of Infectious Disease from June 2008 to June 2015 was conducted in Shanghai, China...
2017: PloS One
https://www.readbyqxmd.com/read/28185618/tuberculosis-a-world-health-organization-perspective
#18
Giovanni Sotgiu, Giorgia Sulis, Alberto Matteelli
Tuberculosis (TB) is an important cause of morbidity and mortality worldwide. The World Health Organization (WHO) has implemented and scaled-up three important global public health strategies (i.e., DOTS, Stop TB, and End TB) to improve the international scenario. Their epidemiological impact was relevant, as they decreased the number of potential new cases of disease and death. However, the emergence and spread of TB/HIV coinfection and multidrug-resistant TB have hindered the progress towards the elimination of TB by 2050...
January 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28185617/mycobacterium-kansasii
#19
James C Johnston, Leslie Chiang, Kevin Elwood
The incidence of Mycobacterium kansasii varies widely over time and by region, but this organism remains one of the most clinically relevant isolated species of nontuberculous mycobacteria. In contrast to other common nontuberculous mycobacteria, M. kansasii is infrequently isolated from natural water sources or soil. The major reservoir appears to be tap water. Infection is likely acquired through the aerosol route, with low infectivity in regions of endemicity. Human-to-human transmission is thought not to occur...
January 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28185538/synthesis-and-biological-evaluation-of-hybrid-1-5-and-2-5-disubstituted-indoles-as-potentially-new-antitubercular-agents
#20
Ana Soares, Mónica S Estevão, M Manuel B Marques, Vasily Kovalishyn, Diogo A R S Latino, João Aires-de-Sousa, Jorge Ramos, Miguel Viveiros, Filomena Martins
BACKGROUND: Tuberculosis (TB) is the second leading cause of mortality worldwide being a highly contagious and insidious illness caused by Mycobacterium tuberculosis, Mtb. Additionally, the emergence of multidrug-resistant and extensively drug-resistant strains of Mtb, together with significant levels of co-infection with HIV and TB (HIV/TB) makes the search for new antitubercular drugs urgent and challenging. METHODS: This work was based on the hypothesis that an active compound could be obtained if substituents present in some other active compounds were attached on a core of an important structure, in this case the indole scaffold, thus generating a hybrid compound...
February 9, 2017: Medicinal Chemistry
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