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Hiv and pharmacokinetics

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https://www.readbyqxmd.com/read/28530033/concomitant-contraceptive-implant-and-efavirenz-use-in-women-living-with-hiv-perspectives-on-current-evidence-and-policy-implications-for-family-planning-and-hiv-treatment-guidelines
#1
REVIEW
Rena C Patel, Chelsea Morroni, Kimberly K Scarsi, Tabitha Sripipatana, James Kiarie, Craig R Cohen
INTRODUCTION: Preventing unintended pregnancies is important among all women, including those living with HIV. Increasing numbers of women, including HIV-positive women, choose progestin-containing subdermal implants, which are one of the most effective forms of contraception. However, drug-drug interactions between contraceptive hormones and efavirenz-based antiretroviral therapy (ART) may reduce implant effectiveness. We present four inter-related perspectives on this issue. DISCUSSION: First, as a case study, we discuss how limited data prompted country-level guidance against the use of implants among women concomitantly using efavirenz in South Africa and its subsequent negative effects on the use of implants in general...
May 11, 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/28507222/meeting-the-goal-of-concurrent-adolescent-and-adult-licensure-of-hiv-prevention-and-treatment-strategies
#2
Michelle Hume, Linda L Lewis, Robert M Nelson
The ability of adolescents to access safe and effective new products for HIV prevention and treatment is optimised by adolescent licensure at the same time these products are approved and marketed for adults. Many adolescent product development programmes for HIV prevention or treatment products may proceed simultaneously with adult phase III development programmes. Appropriately implemented, this strategy is not expected to delay licensure as information regarding product efficacy can often be extrapolated from adults to adolescents, and pharmacokinetic properties of drugs in adolescents are expected to be similar to those in adults...
May 15, 2017: Journal of Medical Ethics
https://www.readbyqxmd.com/read/28507108/safety-pharmacokinetics-and_antiviral-activity-of-a-novel-hiv-antiviral-abx464-in-treatment-na%C3%A3-ve-hiv-infected-subjects-a-phase-ii-randomized-controlled-study
#3
Jean-Marc Steens, Didier Scherrer, Paul Gineste, P Noel Barrett, Supparatpino Kuanchai, Ratanasuwan Winai, Kiat Ruxrungtham, Jamal Tazi, Robert Murphy, Hartmut Ehrlich
We investigated the safety and anti-viral effects of an anti-HIV compound (ABX464) with a unique mechanism of viral replication inhibition. This was a randomized, double blind, placebo controlled, dose- ranging study in treatment naïve HIV infected patients. Participants were assigned to eight groups; each group included 8 subjects receiving either the study compound, ABX464 (n=6) or corresponding placebo (n=2), according to a randomization code. The first dose administered was 25 mg, given once or 3 times a day over a 2 to 3-week period...
May 15, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28483965/pharmacokinetics-of-efavirenz-in-2-3-years-old-children-a-high-dose-of-25-mg-kg-per-day
#4
Claire Pressiat, Madeleine Amorissani-Folquet, Caroline Yonaba, Jean-Marc Treluyer, Désiré Lucien Dahourou, François Eboua, Stéphane Blanche, Véronique Mea-Assande, Naïm Bouazza, Frantz Foissac, Karen Malateste, Sylvie Ouedraogo, Gabrielle Lui, Valériane Leroy, Déborah Hirt
Background: The MONOD ANRS 12206 trial was designated to assess simplification of a successful LPV-based antiretroviral treatment in young HIV-infected children using efavirenz (25 mg/kg/day) to preserve the protease inhibitors class before the age of 3. In this sub-study, EFV concentrations were measured to check the consistency of a 25 mg/kg EFV dose and to compare it with the 2016 FDA recommended dose.Methods: Fifty-two children underwent blood sampling for pharmacokinetic study at 6-month and 12-month after switching to EFV...
May 8, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28481112/structure-based-optimization-of-thiophene-3-2-d-pyrimidine-derivatives-as-potent-hiv-1-non-nucleoside-reverse-transcriptase-inhibitors-with-improved-potency-against-resistance-associated-variants
#5
Dongwei Kang, Zengjun Fang, Boshi Huang, Xueyi Lu, Heng Zhang, Haoran Xu, Zhipeng Huo, Zhongxia Zhou, Zhao Yu, Qing Meng, Gaochan Wu, Xiao Ding, Ye Tian, Dirk Daelemans, Erik De Clercq, Christophe Pannecouque, Peng Zhan, Xinyong Liu
This work follows on from our initial discovery of a series of piperidine-substituted thiophene[3,2-d]pyrimidine HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTI) ( J. Med. Chem. 2016 , 59 , 7991 - 8007 ). In the present study, we designed, synthesized, and biologically tested several series of new derivatives in order to investigate previously unexplored chemical space. Some of the synthesized compounds displayed single-digit nanomolar anti-HIV potencies against wild-type (WT) virus and a panel of NNRTI-resistant mutant viruses in MT-4 cells...
May 15, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28480762/steady-state-pharmacokinetics-of-tenofovir-disoproxil-fumarate-in-human-immunodeficiency-virus-infected-chinese-patients
#6
Xiaoli Du, Huijuan Kou, Qiang Fu, Yanling Li, Zhu Zhu, Taisheng Li
BACKGROUND: The pharmacokinetic (PK) profile of tenofovir disoproxil fumarate in Chinese adults infected with HIV is unknown. RESEARCH DESIGN AND METHODS: A pilot, prospective, open-label study was performed to investigate the steady-state PK profile of tenofovir disoproxil fumarate in 15 Chinese HIV-infected patients among whom eight patients were treated with 300 mg tenofovir disoproxil fumarate, 300 mg lamivudine and 400/100 mg lopinavir/ritonavir, and seven with 300 mg tenofovir disoproxil fumarate, 300 mg lamivudine and 400 mg nevirapine...
May 8, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28472448/markers-of-gut-dysfunction-do-not-explain-low-rifampicin-bioavailability-in-hiv-associated-tb
#7
Christopher Vinnard, Shruthi Ravimohan, Neo Tamuhla, Jotam Pasipanodya, Shashikant Srivastava, Chawangwa Modongo, Nicola M Zetola, Drew Weissman, Tawanda Gumbo, Gregory P Bisson
Background: Rifampicin is the key drug responsible for sterilizing activities in the first-line TB treatment regimen. Damage to the gut during acute and chronic HIV infection may inhibit drug absorptive capacity. We sought to test the hypothesis that markers of intestinal damage, bacterial translocation and systemic immune activation would relate to rifampicin bioavailability among HIV/TB patients. Patients and methods: We conducted a prospective cohort study of rifampicin pharmacokinetics in HIV/TB patients in Gaborone, Botswana...
May 2, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28462920/evaluating-the-association-of-single-nucleotide-polymorphisms-with-tenofovir-exposure-in-a-diverse-prospective-cohort-of-women-living-with-hiv
#8
S M Baxi, R M Greenblatt, P Bacchetti, M Cohen, J A DeHovitz, K Anastos, S J Gange, M A Young, B E Aouizerat
Higher exposure to tenofovir (TFV) increases the risk for kidney function decline, but the impact of genetic factors on TFV exposure is largely unknown. We investigated whether single-nucleotide polymorphisms (SNPs, n=211) in 12 genes are potentially involved in TFV exposure. Participants (n=91) from the Women's Interagency HIV Study, underwent a 24 h intensive pharmacokinetic sampling of TFV after witnessed dose and TFV area under the time-concentration curves (AUCs) were calculated for each participant...
May 2, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28453026/-the-clinical-relevance-of-drug-interactions-in-patients-with-human-immunodeficiency-virus-infection-update-2009-2014
#9
Newar A Giraldo, Pedro Amariles, Daniel E Pino Marín, María José Faus
OBJECTIVE: To update information about drug interactions in patients with HIV/AIDS. METHODS: Comprehensive literature review in MEDLINE/PubMed database from May of 2009 to December of 2014, using the Mesh terms: Anti-retroviral agents and drug interactions or herb-drug interactions or food-drug interactions. Publications with drug interactions in humans, in English or Spanish, and with full text were retrieved. Additionally, citation lists from identified articles were reviewed...
October 2016: Revista Chilena de Infectología: órgano Oficial de la Sociedad Chilena de Infectología
https://www.readbyqxmd.com/read/28448874/regulation-and-roles-of-cd26-dppiv-in-hematopoiesis-and-diseases
#10
REVIEW
Zeynab Aliyari Serej, Abbas Ebrahimi Kalan, Ahmad Mehdipour, Hojjatollah Nozad Charoudeh
Dipeptidyl peptidase IV (DPPIV),(1) on the surface of certain cells, where it is also referred to as CD26, is involved in a vast majority of biological and pathological processes. CD26/DPPIV function contributes to cancer and tumor metastasis as well as inhibition of its expression which alters the expression of immune response-related genes. CD26/DPPIV is a widely distributed multifunctional integral membrane and secreted protein that is defined as early predictive biomarker in HIV, cancer and autoimmunity diseases like diabetes and multiple sclerosis...
April 24, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28443391/atazanavir-sulfate-cobicistat-for-the-treatment-of-hiv-infection
#11
Francisco Antunes
During last two decades several drugs were developed to offer long-term benefits in terms of virologic efficacy, favourable tolerability and toxicity profiles in treatment of HIV infection. Pharmacokinetics boosting of protease inhibitor allows a higher genetic barrier, as few or no drug-resistant mutations are detected in patients with virologic failure. Areas covered: Atazanavir sulfate + cobicistat (ATV/c) was recently approved for the treatment of HIV-1 infection. Bioequivalence between cobicistat (COBI) and ritonavir (RTV) as a pharmacoenhancer of ATV was established...
May 9, 2017: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/28426519/toward-a-universal-antiretroviral-regimen-special-considerations-of-pregnancy-and-breast-feeding
#12
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/28419277/prevention-of-tb-using-rifampicin-plus-isoniazid-reduces-nevirapine-concentrations-in-hiv-exposed-infants
#13
Helen McIlleron, Paolo Denti, Silvia Cohn, Fildah Mashabela, Jennifer D Hoffmann, Saba Shembe, Regina Msandiwa, Lubbe Wiesner, Sithembiso Velaphi, Sanjay G Lala, Richard E Chaisson, Neil Martinson, Kelly E Dooley
Background: Newborns of HIV-infected mothers are given daily doses of nevirapine to prevent HIV-1 acquisition. Infants born to mothers with TB should also receive TB preventive therapy. TB preventive regimens include isoniazid for 6 months or rifampicin plus isoniazid for 3 months (RH preventive therapy). The effect of concomitant RH preventive therapy on nevirapine concentrations in infants is unknown. Patients and methods: Tshepiso was a prospective case-control cohort study of pregnant HIV-infected women with and without TB whose newborn infants received standard doses of nevirapine for HIV prophylaxis...
April 16, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28416548/pharmacokinetics-and-preliminary-safety-of-pod-intravaginal-rings-delivering-the-monoclonal-antibody-vrc01-n-for-hiv-prophylaxis-in-a-macaque-model
#14
Chunxia Zhao, Manjula Gunawardana, Francois Villinger, Marc M Baum, Mariana Remedios-Chan, Thomas R Moench, Larry Zeitlin, Kevin J Whaley, Ognian Bohorov, Thomas J Smith, Deborah J Anderson, John A Moss
The broadly neutralizing antibody (bNAb) VRC01, capable of neutralizing 91% of known HIV-1 isolates in vitro, is a promising candidate microbicide for preventing sexual HIV infection when administered topically to the vagina; however, accessibility to antibody-based prophylactic treatment by target populations in sub-Saharan Africa and other under-developed regions may be limited by the high cost and limited manufacturing capacity of conventionally produced antibodies. Intravaginal rings of the pod design (pod-IVRs) delivering Nicotiana-manufactured VRC01-N over a range of release rates have been developed...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28408224/one-drug-for-two-targets-biological-evaluation-of-antiretroviral-agents-endowed-with-antiproliferative-activity
#15
Lorenzo Botta, Giorgio Maccari, Pierpaolo Calandro, Marika Tiberi, Annalaura Brai, Claudio Zamperini, Filippo Canducci, Mario Chiariello, Rosa Martí-Centelles, Eva Falomir, Miguel Carda
AIDS-related cancer diseases are malignancies with low incidence on healthy people that affect mostly subjects already immunocompromised. The connection between HIV/AIDS and these cancers has not been established yet, but a weakened immune system is certainly the main cause. We envisaged the possibility to screen a small library of compounds synthesized in our laboratory against opportunistic tumors mainly due to HIV infection like Burkitt's Lymphoma. From cellular assays and gene expression analysis we identified two promising compounds...
April 1, 2017: Bioorganic & Medicinal Chemistry Letters
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
#16
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/28384599/the-effect-of-veno-venous-ecmo-on-the-pharmacokinetics-of-ritonavir-darunavir-tenofovir-and-lamivudine
#17
Mohamed A Ghazi Suliman, Kayode Ogungbenro, Christos Kosmidis, Alan Ashworth, Julian Barker, Anita Szabo-Barnes, Andrew Davies, Lee Feddy, Igor Fedor, Tim Hayes, Sarah Stirling, Ignacio Malagon
INTRODUCTION: To our knowledge, there is no published data on the pharmacokinetic (PK) profile of antiretroviral (ART) drugs on patients undergoing extracorporeal membrane oxygenation (ECMO) therapy. We present PK analyses of Ritonavir, Darunavir, Lamivudine and Tenofovir in a patient with HIV who required veno-venous ECMO (VV ECMO). METHODS: Plasma concentrations for Ritonavir, Darunavir, Tenofovir and Lamivudine were obtained while the patient was on ECMO following pre-emptive dose adjustments...
March 12, 2017: Journal of Critical Care
https://www.readbyqxmd.com/read/28382208/etravirine-combined-with-antiretrovirals-other-than-darunavir-ritonavir-for-hiv-1-infected-treatment-experienced-adults-week-48-results-of-a-phase-iv-trial
#18
Eduardo Arathoon, Asad Bhorat, Rodica Silaghi, Herta Crauwels, Ludo Lavreys, Lotke Tambuyzer, Ben Van Baelen, Simon Vanveggel, Magda Opsomer
OBJECTIVE: VIOLIN (TMC125IFD3002; NCT01422330) evaluated the safety, tolerability, and pharmacokinetics of etravirine with antiretrovirals other than darunavir/ritonavir in HIV-1-infected patients. METHODS: In a 48-week, phase IV, single-arm, multicenter study, patients on prior antiretroviral therapy (⩾8 weeks) who needed to change regimen for virologic failure (viral load ⩾ 500 copies/mL) or simplification/adverse events (viral load < 50 copies/mL) received etravirine 200 mg bid with ⩾1 other active antiretroviral, excluding darunavir/ritonavir or only nucleoside/tide reverse transcriptase inhibitors...
2017: SAGE Open Medicine
https://www.readbyqxmd.com/read/28368743/population-pharmacokinetics-analysis-of-vrc01-an-hiv-1-broadly-neutralizing-monoclonal-antibody-in-healthy-adults
#19
Yunda Huang, Lily Zhang, Julie Ledgerwood, Nicole Grunenberg, Robert Bailer, Abby Isaacs, Kelly Seaton, Kenneth H Mayer, Edmund Capparelli, Larry Corey, Peter B Gilbert
The monoclonal antibody VRC01 targets the CD4 binding site of the human immunodeficiency virus (HIV)-1 envelope. In the clinical study HVTN 104 (NCT02165267), 84 HIV-uninfected adults received multiple-dose intravenous (IV) VRC01 (10, 20, 30 or 40 mg/kg) every 4 or 8 weeks or subcutaneous (SC) VRC01 (5 mg/kg) every 2 weeks, and were followed for 32 weeks. We conducted a population pharmacokinetics (popPK) analysis based on 1117 VRC01 serum concentrations using a 2-compartment PK model with first-order elimination; for SC VRC01 a depot compartment with a first-order absorption rate constant was also included...
April 3, 2017: MAbs
https://www.readbyqxmd.com/read/28356041/recent-advances-in-antiretroviral-agents-potent-integrase-inhibitors
#20
Mina Psichogiou, Garyphalia Poulakou, Dimitrios Basoulis, Dimitrios Paraskevis, Antonios Markogiannakis, George L Daikos
Integrase strand transfer inhibitors (INSTIs) belong to a novel class of antiretroviral agents that have emerged as the new first-line treatments. Three such compounds are currently available, raltegravir, elvitegravir, dolutegravir and two more under development, bictegravir and cabotegravir. These compounds share the same mode of action but exhibit different pharmacokinetic/ pharmacodynamic properties, and drug-drug interactions. A series of studies in the past decade have established their efficacy compared to previous regimens, both in treatment-naïve and experienced patients...
March 29, 2017: Current Pharmaceutical Design
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