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Hiv and pharmacokinetics

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https://www.readbyqxmd.com/read/28426519/toward-a-universal-antiretroviral-regimen-special-considerations-of-pregnancy-and-breast-feeding
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/28349328/the-effect-of-food-on-doravirine-bioavailability-results-from-two-pharmacokinetic-studies-in-healthy-subjects
#10
Martin O Behm, Ka Lai Yee, Rachael Liu, Vanessa Levine, Deborah Panebianco, Paul Fackler
BACKGROUND AND OBJECTIVE: Doravirine is a novel non-nucleoside reverse transcriptase inhibitor being developed for the treatment of HIV-1. In two open-label, single-dose, randomized, two-period, crossover trials, the bioavailability of doravirine administered alone or in a fixed-dose combination (FDC) was determined under fed and fasted conditions. METHODS: Doravirine 100 mg alone or with lamivudine and tenofovir disoproxil fumarate (each 300 mg) were administered to healthy subjects fasted or 30 min after a high-fat, high-calorie breakfast...
March 27, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28348149/pharmacokinetics-and-placental-transfer-of-elvitegravir-and-dolutegravir-and-other-antiretrovirals-during-pregnancy
#11
Bassam H Rimawi, Erica Johnson, Augustine Rajakumar, Sijia Tao, Yong Jiang, Scott Gillespie, Raymond F Schinazi, Mark Mirochnick, Martina L Badell, Rana Chakraborty
The integrase inhibitors, elvitegravir (EVG) and dolutegravir (DTG), rapidly decrease plasma HIV-1 viral load, a key factor in the prevention of maternal-to-fetal transmission of HIV-1. No data have been reported on the concentration of these drugs in cord blood, maternal peripheral blood mononuclear cells (PBMC) concentrations or placental tissue in pregnant women. We present in vivo pharmacokinetic data on antiretrovirals (ARV) within maternal and cord blood, and within placentae from HIV-1-infected pregnant women...
March 27, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28344011/the-epidemiology-pathogenesis-transmission-diagnosis-and-management-of-multidrug-resistant-extensively-drug-resistant-and-incurable-tuberculosis
#12
REVIEW
Keertan Dheda, Tawanda Gumbo, Gary Maartens, Kelly E Dooley, Ruth McNerney, Megan Murray, Jennifer Furin, Edward A Nardell, Leslie London, Erica Lessem, Grant Theron, Paul van Helden, Stefan Niemann, Matthias Merker, David Dowdy, Annelies Van Rie, Gilman K H Siu, Jotam G Pasipanodya, Camilla Rodrigues, Taane G Clark, Frik A Sirgel, Aliasgar Esmail, Hsien-Ho Lin, Sachin R Atre, H Simon Schaaf, Kwok Chiu Chang, Christoph Lange, Payam Nahid, Zarir F Udwadia, C Robert Horsburgh, Gavin J Churchyard, Dick Menzies, Anneke C Hesseling, Eric Nuermberger, Helen McIlleron, Kevin P Fennelly, Eric Goemaere, Ernesto Jaramillo, Marcus Low, Carolina Morán Jara, Nesri Padayatchi, Robin M Warren
Global tuberculosis incidence has declined marginally over the past decade, and tuberculosis remains out of control in several parts of the world including Africa and Asia. Although tuberculosis control has been effective in some regions of the world, these gains are threatened by the increasing burden of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis. XDR tuberculosis has evolved in several tuberculosis-endemic countries to drug-incurable or programmatically incurable tuberculosis (totally drug-resistant tuberculosis)...
March 15, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28341759/a-phase-ib-study-of-sorafenib-bay-43-9006-in-patients-with-kaposi-sarcoma
#13
Thomas S Uldrick, Priscila H Gonçalves, Kathleen M Wyvill, Cody J Peer, Wendy Bernstein, Karen Aleman, Mark N Polizzotto, David Venzon, Seth M Steinberg, Vickie Marshall, Denise Whitby, Richard F Little, John J Wright, Michelle A Rudek, William D Figg, Robert Yarchoan
LESSONS LEARNED: Oral targeted agents are desirable for treatment of Kaposi sarcoma (KS); however, in patients with HIV, drug-drug interactions must be considered. In this study to treat KS, sorafenib was poorly tolerated at doses less than those approved by the U.S. Food and Drug Administration for hepatocellular carcinoma and other cancers, and showed only modest activity.Sorafenib's metabolism occurs via the CYP3A4 pathway, which is inhibited by ritonavir, a commonly used antiretroviral agent used by most patients in this study...
March 24, 2017: Oncologist
https://www.readbyqxmd.com/read/28335648/inflammation-and-pharmacokinetics-potential-implications-for-hiv-infection
#14
Sharon M Seifert, Jose R Castillo-Mancilla, Kristine M Erlandson, Peter L Anderson
The physiological changes accompanying inflammation may alter the pharmacokinetics (PK) of certain medications. Individuals infected with HIV have chronically elevated inflammatory markers despite viral suppression following effective antiretroviral therapy (ART), as well as age-related inflammation. Understanding the potential clinical implications of inflammation on the PK of medications is important for understanding dose-response relationships and necessitates future research. Areas covered: An extensive literature search was carried out using PubMed and associated bibliographies to summarize the current state of knowledge regarding altered PK in response to inflammation and its application to the field of HIV...
March 24, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28334018/development-of-an-evidence-evaluation-and-synthesis-system-for-drug-drug-interactions-and-its-application-to-a-systematic-review-of-hiv-and-malaria-co-infection
#15
Kay Seden, Sara Gibbons, Catia Marzolini, Jonathan M Schapiro, David M Burger, David J Back, Saye H Khoo
BACKGROUND: In all settings, there are challenges associated with safely treating patients with multimorbidity and polypharmacy. The need to characterise, understand and limit harms resulting from medication use is therefore increasingly important. Drug-drug interactions (DDIs) are prevalent in patients taking antiretrovirals (ARVs) and if unmanaged, may pose considerable risk to treatment outcome. One of the biggest challenges in preventing DDIs is the substantial gap between theory and clinical practice...
2017: PloS One
https://www.readbyqxmd.com/read/28317117/comparative-pharmacokinetic-evaluation-of-lopinavir-and-lopinavir-loaded-solid-lipid-nanoparticles-in-hepatic-impaired-rat-model
#16
Punna Rao Ravi, Rahul Vats
OBJECTIVE: Drug-induced hepatotoxicity is a major cause of concern in patients receiving HIV/TB co-treatment. Lopinavir (LPV), an anti-HIV drug, shows poor plasma exposure due to hepatic first-pass metabolism. In this study, we investigated the effect of hepatotoxicity on pharmacokinetics of free LPV and LPV-loaded solid lipid nanoparticles (LPV SLNs) in male Wistar rats. METHODS: Hepatic impairment model in rats was developed by injecting CCl4 (i.p., 2 ml/kg). Comparative pharmacokinetic (n = 5) and tissue distribution studies (n = 3) were conducted following oral administration (20 mg/kg) of free LPV and LPV SLNs in normal and hepatic impaired rats...
March 19, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28296019/health-care-provider-communication-training-in-rural-tanzania-empowers-hiv-infected-patients-on-antiretroviral-therapy-to-discuss-adherence-problems
#17
S Erb, E Letang, T R Glass, A Natamatungiro, D Mnzava, H Mapesi, M Haschke, U Duthaler, B Berger, L Muri, J Bader, C Marzolini, L Elzi, T Klimkait, W Langewitz, M Battegay
OBJECTIVES: Self-reported adherence assessment in HIV-infected patients on antiretroviral therapy (ART) is challenging and may overestimate adherence. The aim of this study was to improve the ability of health care providers to elicit patients' reports of nonadherence using a "patient-centred" approach in a rural sub-Saharan African setting. METHODS: A prospective interventional cohort study of HIV-infected patients on ART for ≥ 6 months attending an HIV clinic in rural Tanzania was carried out...
March 13, 2017: HIV Medicine
https://www.readbyqxmd.com/read/28293270/effect-of-moringa-oleifera-lam-leaf-powder-on-the-pharmacokinetics-of-nevirapine-in-hiv-infected-adults-a-one-sequence-cross-over-study
#18
Tsitsi G Monera-Penduka, Charles C Maponga, Alan R Wolfe, Lubbe Wiesner, Gene D Morse, Charles F B Nhachi
BACKGROUND: Moringa oleifera Lam., an herb commonly consumed by HIV-infected people on antiretroviral therapy, inhibits cytochrome P450 3A4, 1A2 and 2D6 activity in vitro; and may alter the pharmacokinetics (PK) of antiretroviral drugs metabolized via the same pathways. However, in vitro drug interaction activity may not translate to a clinically significant effect. Therefore, the effect of moringa leaf powder on the PK of nevirapine in HIV-infected people was investigated. METHODS: Adult patients at steady-state dosing with nevirapine were admitted for 12-h intensive PK sampling following a 21-day herbal medicine washout...
2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28288665/effect-of-moringa-oleifera-lam-leaf-powder-on-the-pharmacokinetics-of-nevirapine-in-hiv-infected-adults-a-one-sequence-cross-over-study
#19
Tsitsi G Monera-Penduka, Charles C Maponga, Alan R Wolfe, Lubbe Wiesner, Gene D Morse, Charles F B Nhachi
BACKGROUND: Moringa oleifera Lam., an herb commonly consumed by HIV-infected people on antiretroviral therapy, inhibits cytochrome P450 3A4, 1A2 and 2D6 activity in vitro; and may alter the pharmacokinetics (PK) of antiretroviral drugs metabolized via the same pathways. However, in vitro drug interaction activity may not translate to a clinically significant effect. Therefore, the effect of moringa leaf powder on the PK of nevirapine in HIV-infected people was investigated. METHODS: Adult patients at steady-state dosing with nevirapine were admitted for 12-h intensive PK sampling following a 21-day herbal medicine washout...
March 14, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28287204/-biliary-and-kidney-lithiasis-during-treatment-with-daclatasvir-sofosbuvir-ribavirin-and-atazanavir-ritonavir-abacavir-lamivudine-in-an-hiv-hcv-genotype-4-infected-patient-a-case-report
#20
Andrea Vavassori, Paola Lanza, Ilaria Izzo, Salvatore Casari, Silvia Odolini, Serena Zaltron, Elena Festa, Francesco Castelli
New Direct-acting Antiviral Agents (DAA)-based anti-HCV therapies currently provide extraordinary opportunities to cure patients. Drug-drug interactions are however a real challenge during treatment. In particular, in HIV-infected patients in cART, DAA choice is limited by such interactions, which can result both in reduced efficacy and toxicity. We report the case of a HIV-infected patient on cART with atazanavir/ritonavir/abacavir/lamivudine, who presented kidney and biliary lithiasis, the latter treated with endoscopic retrograde cholangiopancreatography and endoscopic biliary sphincterotomy, after beginning anti-HCV treatment with daclatasvir/sofosbuvir/ribavirin...
February 2017: Recenti Progressi in Medicina
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