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https://www.readbyqxmd.com/read/28230617/acute-kidney-injury-following-efavirenz-tenofovir-disoproxil-fumarate-emtricitabine-atripla%C3%A2-overdose
#1
Thomas Havenith, David Burger, Maarten Visschers, Jolanda Schippers, Astrid Oude Lashof
We describe a patient with acute renal failure and irreversible kidney damage after an overdose with the fixed dose combination of efavirenz/tenofovir disoproxil fumarate/emtricitabine (Atripla). The acute kidney injury was most probably caused by tenofovir. Efavirenz and emtricitabine seemed relatively safe in overdose. The pharmacokinetics in overdose of all three drugs and the effect of hemodialysis on the tenofovir clearance were studied by measuring the plasma concentrations and by the use of clinical pharmacokinetic software...
February 20, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28225830/ex-vivo-activation-of-cd4-t-cells-from-donors-on-suppressive-art-can-lead-to-sustained-production-of-infectious-hiv-1-from-a-subset-of-infected-cells
#2
John K Bui, Elias K Halvas, Elizabeth Fyne, Michele D Sobolewski, Dianna Koontz, Wei Shao, Brian Luke, Feiyu F Hong, Mary F Kearney, John W Mellors
The fate of HIV-infected cells after reversal of proviral latency is not well characterized. Simonetti, et al. recently showed that CD4+ T-cells containing intact proviruses can clonally expand in vivo and produce low-level infectious viremia. We hypothesized that reversal of HIV latency by activation of CD4+ T-cells can lead to the expansion of a subset of virus-producing cells rather than their elimination. We established an ex vivo cell culture system involving stimulation of CD4+ T-cells from donors on suppressive antiretroviral therapy (ART) with PMA/ionomycin (day 1-7), followed by rest (day 7-21), and then repeat stimulation (day 21-28), always in the presence of high concentrations of raltegravir and efavirenz to effectively block new cycles of viral replication...
February 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28222098/multicenter-study-of-skin-rashes-and-hepatotoxicity-in-antiretroviral-na%C3%A3-ve-hiv-positive-patients-receiving-non-nucleoside-reverse-transcriptase-inhibitor-plus-nucleoside-reverse-transcriptase-inhibitors-in-taiwan
#3
Pei-Ying Wu, Chien-Yu Cheng, Chun-Eng Liu, Yi-Chien Lee, Chia-Jui Yang, Mao-Song Tsai, Shu-Hsing Cheng, Shih-Ping Lin, De-Yu Lin, Ning-Chi Wang, Yi-Chieh Lee, Hsin-Yun Sun, Hung-Jen Tang, Chien-Ching Hung
OBJECTIVES: Two nucleos(t)ide reverse-transcriptase inhibitors (NRTIs) plus 1 non-NRTI (nNRTI) remain the preferred or alternative combination antiretroviral therapy (cART) for antiretroviral-naive HIV-positive patients in Taiwan. The three most commonly used nNRTIs are nevirapine (NVP), efavirenz (EFV) and rilpivirine (RPV). This study aimed to determine the incidences of hepatotoxicity and skin rashes within 4 weeks of initiation of cART containing 1 nNRTI plus 2 NRTIs. METHODS: Between June, 2012 and November, 2015, all antiretroviral-naive HIV-positive adult patients initiating nNRTI-containing cART at 8 designated hospitals for HIV care were included in this retrospective observational study...
2017: PloS One
https://www.readbyqxmd.com/read/28213595/qualitative-study-of-the-breather-trial-short-cycle-antiretroviral-therapy-is-it-acceptable-to-young-people-living-with-hiv
#4
Sarah Bernays, Sara Paparini, Janet Seeley, Stella Namukwaya Kihika, Diana Gibb, Tim Rhodes
OBJECTIVES: A qualitative study of the BREATHER (PENTA 16) randomised clinical trial, which compared virological control of Short Cycle Therapy (SCT) (5 days on: 2 days off) with continuous efavirenz (EFV)-based antiretroviral therapy (CT) in children and young people (aged 8-24) living with HIV with viral load <50 c/mL to examine adaptation, acceptability and experience of SCT to inform intervention development. SETTING: Paediatric HIV clinics in the UK (2), Ireland (1), the USA (1) and Uganda (1)...
February 17, 2017: BMJ Open
https://www.readbyqxmd.com/read/28207816/hiv-drug-therapy-duration-a-swedish-real-world-nationwide-cohort-study-on-infcarehiv-2009-2014
#5
Amanda Häggblom, Stefan Lindbäck, Magnus Gisslén, Leo Flamholc, Bo Hejdeman, Andreas Palmborg, Amy Leval, Eva Herweijer, Sverrir Valgardsson, Veronica Svedhem
BACKGROUND: As HIV infection needs a lifelong treatment, studying drug therapy duration and factors influencing treatment durability is crucial. The Swedish database InfCareHIV includes high quality data from more than 99% of all patients diagnosed with HIV infection in Sweden and provides a unique opportunity to examine outcomes in a nationwide real world cohort. METHODS: Adult patients who started a new therapy defined as a new 3rd agent (all antiretrovirals that are not N[t]RTIs) 2009-2014 with more than 100 observations in treatment-naive or treatment-experienced patients were included...
2017: PloS One
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
#6
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/28194792/semisimultaneous-midazolam-administration-to-evaluate-the-time-course-of-cyp3a-activation-by-a-single-oral-dose-of-efavirenz
#7
Gerd Mikus, Tilman Heinrich, Julia Bödigheimer, Claudia Röder, Anne-Kathrin Matthee, Johanna Weiss, Jürgen Burhenne, Walter E Haefeli
This study aimed to assess whether a single oral dose of the nonnucleoside reverse transcriptase inhibitor efavirenz can alter CYP3A in vivo. In 12 healthy participants individual CYP3A activity was quantified using a semisimultaneous methodology (midazolam orally and 6 hours later intravenously) both alone and during a period of 22 days after a single oral dose of 400 mg efavirenz. Twelve hours after efavirenz administration, midazolam apparent oral clearance was significantly increased by 70%, and midazolam systemic clearance after intravenous administration was significantly increased by 27%...
February 14, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28192529/first-line-antiretroviral-drug-discontinuations-in-children
#8
Melony Fortuin-de Smidt, Reneé de Waal, Karen Cohen, Karl-Günter Technau, Kathryn Stinson, Gary Maartens, Andrew Boulle, Ehimario U Igumbor, Mary-Ann Davies
INTRODUCTION: There are a limited number of paediatric antiretroviral drug options. Characterising the long term safety and durability of different antiretrovirals in children is important to optimise management of HIV infected children and to determine the estimated need for alternative drugs in paediatric regimens. We describe first-line antiretroviral therapy (ART) durability and reasons for discontinuations in children at two South African ART programmes, where lopinavir/ritonavir has been recommended for children <3 years old since 2004, and abacavir replaced stavudine as the preferred nucleoside reverse transcriptase inhibitor in 2010...
2017: PloS One
https://www.readbyqxmd.com/read/28188763/hiv-antiretroviral-drug-efavirenz-induces-anxiety-like-and-depression-like-behavior-in-rats-evaluation-of-neurotransmitter-alterations-in-the-striatum
#9
Giuliana Ignácio Teixeira Cavalcante, Adriano José Maia Chaves Filho, Maria Isabel Linhares, Camila Nayane de Carvalho Lima, Edith Teles Venâncio, Emiliano Ricardo Vasconcelos Rios, Francisca Cléa Florenço de Souza, Silvânia Maria Mendes Vasconcelos, Danielle Macêdo, Marta Maria de França Fonteles
Efavirenz (EFV) is an effective antiretroviral drug with a favorable pharmacokinetic profile and widely used in combination regimens to treat HIV infection. However, there are major concerns about the safety of this drug. Patients treated with EFV often experience neuropsychiatric adverse effects, which frequently lead to switching to alternative EFV-free regimens. The mechanisms involved in the central action of EFV are intrinsically unclear. Thus, this study aimed to investigate the effects of acute and subchronic (2 weeks) EFV administration in a series of behavioral tests for anxiety-like and depression-like behavior in healthy rats...
February 7, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28187506/the-effect-of-gene-variants-on-levonorgestrel-pharmacokinetics-when-combined-with-antiretroviral-therapy-containing-efavirenz-or-nevirapine
#10
M Neary, M Lamorde, A Olagunju, K M Darin, C Merry, P Byakika-Kibwika, D J Back, M Siccardi, A Owen, K K Scarsi
Reduced levonorgestrel concentrations from the levonorgestrel contraceptive implant was previously seen when given concomitantly with efavirenz. We sought to assess whether single nucleotide polymorphisms (SNPs) in genes involved in efavirenz and nevirapine metabolism were linked to these changes in levonorgestrel concentration. SNPs in CYP2B6, CYP2A6, NR1I2 and NR1I3 were analysed. Associations of participant demographics and genotype with levonorgestrel pharmacokinetics were evaluated in HIV-positive women using the levonorgestrel implant plus efavirenz- or nevirapine-based ART, in comparison to ART-naïve women using multivariate linear regression...
February 10, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28187497/antiretroviral-therapy-with-efavirenz-accentuates-pregnancy-associated-reduction-of-dihydroartemisinin-piperaquine-exposure-during-malaria-chemoprevention
#11
Richard Kajubi, Liusheng Huang, Prasanna Jagannathan, Nona Chamankhah, Moses Were, Theodore Ruel, Catherine A Koss, Abel Kakuru, Norah Mwebaza, Moses Kamya, Diane Havlir, Grant Dorsey, Philip J Rosenthal, Francesca T Aweeka
Dihydroartemisinin (DHA)-piperaquine is promising for malaria chemoprevention in pregnancy. We assessed impacts of pregnancy and efavirenz-based antiretroviral therapy on exposure to DHA and piperaquine in pregnant Ugandan women. Intensive sampling was performed at 28 weeks gestation in 31 HIV-uninfected pregnant women, in 27 HIV-infected pregnant women receiving efavirenz, and in 30 HIV-uninfected non-pregnant women. DHA peak concentration and area under the concentration time curve (AUC0-8hr ) were 50% and 47% lower, respectively, and piperaquine AUC0-21d was 40% lower in pregnant women compared to non-pregnant women...
February 10, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28177134/the-influence-of-combination-use-of-cyp450-inducers-on-the-pharmacokinetics-of-voriconazole-a-systematic-review
#12
REVIEW
T-Y Li, W Liu, K Chen, S-Y Liang, F Liu
WHAT IS KNOWN AND OBJECTIVES: Voriconazole is a triazole antifungal agent and is extensively metabolized via cytochrome P450 (CYP450); therefore, special precautions need to be taken when co-administered with a known CYP450 inducer, which may lead to treatment failure. The influence of some CYP450 inducers on the pharmacokinetics of voriconazole has been described in previous studies, but a systematic review was lacking. In this study, we carried out a systematic review to assess the influence of CYP450 inducers on the pharmacokinetic (PK) parameters of voriconazole...
February 8, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28175315/effect-of-rifampicin-and-efavirenz-on-moxifloxacin-concentrations-when-co-administered-in-patients-with-drug-susceptible-tb
#13
Anushka Naidoo, Maxwell Chirehwa, Helen McIlleron, Kogieleum Naidoo, Sabiha Essack, Nonhlanhla Yende-Zuma, Eddy Kimba-Phongi, John Adamson, Katya Govender, Nesri Padayatchi, Paolo Denti
No abstract text is available yet for this article.
February 8, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28167742/structural-and-preclinical-studies-of-computationally-designed-non-nucleoside-reverse-transcriptase-inhibitors-for-treating-hiv-infection
#14
Shalley N Kudalkar, Jagadish Beloor, Albert H Chan, Won-Gil Lee, William L Jorgensen, Priti Kumar, Karen S Anderson
The clinical benefits of human immunodeficiency virus type 1 (HIV-1) non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs) are hindered by their unsatisfactory pharmacokinetic (PK) properties along with the rapid development of drug-resistant variants. However, the clinical efficacy of these inhibitors can be improved by developing compounds with enhanced pharmacological profiles and heightened antiviral activity. We used computational and structure-guided design to develop two next-generation NNRTI drug candidates, compounds I and II, which are members of a class of catechol diethers...
February 6, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28161530/effects-of-cholecalciferol-supplementation-on-serum-and-urinary-vitamin-d-metabolites-and-binding-protein-in-hiv-infected-youth
#15
Allison Ross Eckard, Myrtle Thierry-Palmer, Natalia Silvestrov, Julia C Rosebush, Mary Ann O'Riordan, Julie E Daniels, Monika Uribe-Leitz, Danielle Labbato, Joshua H Ruff, Ravinder J Singh, Vin Tangpricha, Grace A McComsey
Vitamin D insufficiency is widespread in HIV-infected patients. HIV and/or antiretroviral therapy (ART), particularly efavirenz (EFV), may interfere with vitamin D metabolism. However, few data from randomized, controlled trials exist. Here, we investigate changes in vitamin D metabolites and binding protein (VDBP) after 6 months of supplementation in a randomized, active-control, double-blind trial investigating 2 different monthly cholecalciferol (vitamin D3) doses [60,000 (medium) or 120,000 (high) IU/month] vs...
February 1, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28155312/confirmation-of-factors-that-influence-antiretroviral-regimen-change-and-the-subsequent-patient-outcomes-at-a-regional-hospital-in-rural-kwazulu-natal
#16
Vereesha Soorju, Panjasaram Naidoo
BACKGROUND: Treatment failure (TF) and adverse drug reactions (ADRs) are the main indications for antiretroviral therapy (ART) regimen change. Identification of factors influencing regimen change and subsequent health outcomes of patients after regimen change is essential in providing a sustainable and effective antiretroviral roll-out campaign. AIM: To confirm the factors that influence antiretroviral regimen change and to evaluate patient outcomes post regimen change...
October 31, 2016: African Journal of Primary Health Care & Family Medicine
https://www.readbyqxmd.com/read/28147708/tolerability-of-central-nervous-system-symptoms-among-hiv-1-infected-efavirenz-users-analysis-of-patient-electronic-medical-record-data
#17
Lisa Rosenblatt, Michael S Broder, Tanya G K Bentley, Eunice Chang, Sheila R Reddy, Elya Papoyan, Joel Myers
Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor indicated for treatment of HIV-1 infection. Despite concern over EFV tolerability in clinical trials and practice, particularly related to central nervous system (CNS) adverse events, some observational studies have shown high rates of EFV continuation at one year and low rates of CNS-related EFV substitution. The objective of this study was to further examine the real-world rate of CNS-related EFV discontinuation in antiretroviral therapy naïve HIV-1 patients...
February 1, 2017: AIDS Care
https://www.readbyqxmd.com/read/28145050/cytochrome-2b6-polymorphism-and-efavirenz-induced-central-nervous-system-symptoms-a-substudy-of-the-anrs-alize-trial
#18
S Gallien, V Journot, M-A Loriot, H Sauvageon, P Morlat, J Reynes, V Reliquet, G Chêne, J-M Molina
OBJECTIVES: Single nucleotide polymorphisms in the cytochrome P450 (CYP) 2B6 gene have been associated with high interindividual variation in efavirenz pharmacokinetics. However, clinical data on the relationship of CYP2B6 polymorphisms with the occurrence of efavirenz-induced central nervous system (CNS) symptoms are limited. METHODS: We analysed four polymorphisms in the CYP2B6 (516 G>T), CYP3A5 (6986 A>G) and ATP-binding cassette, sub-family B, member 1 (ABCB1) (2677 G>T/A and 3435 C>T) genes in HIV-infected adults virologically suppressed on a protease inhibitor-based regimen who switched to a regimen containing emtricitabine, didanosine and efavirenz in the setting of the ANRS ALIZE trial...
February 1, 2017: HIV Medicine
https://www.readbyqxmd.com/read/28134057/hiv-viral-kinetics-and-t-cell-dynamics-in-antiretroviral-na%C3%A3-ve-persons-starting-an-integrase-strand-transfer-inhibitor-and-protease-inhibitor-regimen
#19
Maile Y Karris, Sonia Jain, Tyler R C Day, Josué Pérez-Santiago, Miguel Goicoechea, Michael P Dubé, Xiaoying Sun, Celsa Spina, Eric S Daar, Richard H Haubrich, Sheldon Morris
BACKGROUND: Nucleos(t)ide reverse transcriptase inhibitor (NRTI)-sparing regimens may potentially minimize antiretroviral (ART) toxicities, but demonstrate mixed efficacy and toxicity results. The impact of an integrase strand transfer inhibitor (INSTI) and protease inhibitor (PI) regimen on HIV viral dynamics and T cell kinetics remains underdescribed. OBJECTIVE: To compare the effect of raltegravir + ritonavir boosted lopinavir (RAL + LPV/r) to efavirenz/tenofovir disoproxil fumarate/emtricitabine (EFV/TDF/FTC) on HIV kinetics and T cell dynamics...
January 30, 2017: HIV Clinical Trials
https://www.readbyqxmd.com/read/28125999/herv-k-activation-is-strictly-required-to-sustain-cd133-melanoma-cells-with-stemness-features
#20
Ayele Argaw-Denboba, Emanuela Balestrieri, Annalucia Serafino, Chiara Cipriani, Ilaria Bucci, Roberta Sorrentino, Ilaria Sciamanna, Alessandra Gambacurta, Paola Sinibaldi-Vallebona, Claudia Matteucci
BACKGROUND: Melanoma is a heterogeneous tumor in which phenotype-switching and CD133 marker have been associated with metastasis promotion and chemotherapy resistance. CD133 positive (CD133+) subpopulation has also been suggested as putative cancer stem cell (CSC) of melanoma tumor. Human endogenous retrovirus type K (HERV-K) has been described to be aberrantly activated during melanoma progression and implicated in the etiopathogenesis of disease. Earlier, we reported that stress-induced HERV-K activation promotes cell malignant transformation and reduces the immunogenicity of melanoma cells...
January 26, 2017: Journal of Experimental & Clinical Cancer Research: CR
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