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https://www.readbyqxmd.com/read/28626835/disrupted-er-to-golgi-trafficking-underlies-anti-hiv-drugs-and-alcohol-induced-cellular-stress-and-hepatic-injury
#1
Hui Han, Yuxin He, Jay Hu, Rhema Lau, Harrison Lee, Cheng Ji
Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are involved in anti-human immunodeficiency virus (HIV) drugs and alcohol-induced liver disease in a significant number of patients infected with HIV. However, the precise mechanism by which the drugs and alcohol cause ER stress remains elusive. We found that ritonavir-boosted lopinavir (RL) activated two canonical UPR branches without activation of the third canonical activating transcription factor 6 (ATF6) branch in either HepG2 cells or primary mouse hepatocytes...
April 2017: Hepatol Commun
https://www.readbyqxmd.com/read/28592814/impairment-of-the-activin-a-autocrine-loop-by-lopinavir-reduces-self-renewal-of-distinct-human-adipose-progenitors
#2
Christophe Ravaud, Martin Paré, Stéphane Azoulay, Christian Dani, Annie Ladoux
Maintenance of the adipose tissue requires a proper balance between self-renewal and differentiation of adipose progenitors (AP). Any deregulation leads either to fat overexpansion and obesity or fat loss and consequent lipodystrophies. Depending on the fat pad location, APs and adipocytes are heterogeneous. However, information on the pharmacological sensitivity of distinct APs to drugs known to alter the function of adipose tissue, especially HIV protease inhibitors (PIs) is scant. Here we show that PIs decreased proliferation and clonal expansion of APs, modifying their self-renewal potential...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28591025/neurocognitive-development-in-hiv-positive-children-is-correlated-with-plasma-viral-loads-in-early-childhood
#3
Valentin Weber, Daniel Radeloff, Bianca Reimers, Emilia Salzmann-Manrique, Peter Bader, Dirk Schwabe, Christoph Königs
Because of neurocognitive impairments in perinatally human immunodeficiency virus (HIV)-infected children and adolescents, this study aimed to demonstrate the effect of plasma viral loads and early initiation of sufficient combined antiretroviral therapy (cART) on neurocognitive development.In total, 14 perinatally infected HIV-positive children (median age 8.24 years [range: 6.0-16.74]) receiving lopinavir/ritonavir (LPV/r)-based ART underwent neurocognitive testing using the Wechsler Intelligence Score for Children, 4th Edition (WISC-IV)...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28582463/drug-resistance-testing-through-remote-genotyping-and-predicted-treatment-options-in-human-immunodeficiency-virus-type-1-infected-tanzanian-subjects-failing-first-or-second-line-antiretroviral-therapy
#4
Jenny Svärd, Sabina Mugusi, Doreen Mloka, Ujjwal Neogi, Genny Meini, Ferdinand Mugusi, Francesca Incardona, Maurizio Zazzi, Anders Sönnerborg
INTRODUCTION: Antiretroviral therapy (ART) has been successfully introduced in low-middle income countries. However an increasing rate of ART failure with resistant virus is reported. We therefore described the pattern of drug resistance mutations at antiretroviral treatment (ART) failure in a real-life Tanzanian setting using the remote genotyping procedure and thereafter predicted future treatment options using rule-based algorithm and the EuResist bioinformatics predictive engine. According to national guidelines, the default first-line regimen is tenofovir + lamivudine + efavirenz, but variations including nevirapine, stavudine or emtricitabine can be considered...
2017: PloS One
https://www.readbyqxmd.com/read/28579821/opioid-analgesics-related-pharmacokinetic-drug-interactions-from-the-perspectives-of-evidence-based-on-randomized-controlled-trials-and-clinical-risk-management
#5
REVIEW
Xiu-Qin Feng, Ling-Ling Zhu, Quan Zhou
BACKGROUND: Multimorbidity results in complex polypharmacy which may bear a risk of drug interactions. A better understanding of opioid analgesics combination therapy used for pain management could help warrant medication safety, efficacy, and economic relevance. Until now there has been no review summarizing the opioid analgesics-related pharmacokinetic drug interactions from the perspective of evidence based on randomized controlled trials (RCTs). METHOD: A literature search was performed using PubMed, MEDLINE, and the Cochrane Library, using a PRISMA flowchart...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28569994/physiologically-based-pharmacokinetic-modeling-for-predicting-the-effect-of-intrinsic-and-extrinsic-factors-on-darunavir-or-lopinavir-exposure-coadministered-with-ritonavir
#6
Christian Wagner, Ping Zhao, Vikram Arya, Charu Mullick, Kimberly Struble, Stanley Au
Management of comorbidities and medications is complex in HIV-1-infected patients. The overall objective of this project was to develop separate physiologically based pharmacokinetic (PBPK) substrate models for the protease inhibitors darunavir and lopinavir. These protease inhibitors are used in the treatment of HIV infection. Both darunavir and lopinavir are coadministered with another medication that inhibits cytochrome (CYP) 3A. The current project focused on PBPK modeling for darunavir and lopinavir coadministered with ritonavir...
June 1, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28566227/boosted-protease-inhibitor-monotherapy-versus-boosted-protease-inhibitor-plus-lamivudine-dual-therapy-as-second-line-maintenance-treatment-for-hiv-1-infected-patients-in-sub-saharan-africa-anrs12-286-mobidip-a-multicentre-randomised-parallel-open-label-superiority
#7
Laura Ciaffi, Sinata Koulla-Shiro, Adrien Bruno Sawadogo, Cheik Tidiane Ndour, Sabrina Eymard-Duvernay, Pretty Rosereine Mbouyap, Liliane Ayangma, Jacques Zoungrana, Ndeye Fatou Ngom Gueye, Mohamadou Diallo, Suzanne Izard, Guillaume Bado, Coumba Toure Kane, Avelin Fobang Aghokeng, Martine Peeters, Pierre Marie Girard, Vincent Le Moing, Jacques Reynes, Eric Delaporte
BACKGROUND: Despite satisfactory efficacy of WHO-recommended second-line antiretroviral treatment for patients with HIV in low-income countries, the need for simplified, low-cost, and less-toxic maintenance strategies remains high. We compared boosted protease inhibitor monotherapy with dual therapy with boosted protease inhibitor plus lamivudine in patients on second-line antiretrovial therapy (ART). METHODS: We did a multicentre, randomised, parallel, open-label, superiority, trial in the HIV services of five hospitals in sub-Saharan Africa (Yaoundé, Cameroon; Dakar, Senegal; and Bobo Dioulasso, Burkina Faso)...
May 26, 2017: Lancet HIV
https://www.readbyqxmd.com/read/28557187/automated-high-throughput-analysis-of-antiretroviral-drugs-in-dried-blood-spots
#8
U Duthaler, B Berger, S Erb, M Battegay, E Letang, S Gaugler, S Krähenbühl, M Haschke
For therapeutic drug monitoring (TDM) in remote settings, dried blood spots (DBS) are particularly advantageous, as blood sample collection and handling is uncomplicated. The aim of this study was to develop and validate an automated extraction method for the analysis of nevirapine, efavirenz, and lopinavir in DBS samples. Automated extraction was performed with methanol:water (70:30 v/v), using a DBS-MS 500 autosampler coupled to a LC-MS/MS system. The autosampler used digital images of each DBS to position the extraction head, sprayed 10 μL internal standard (IS) onto each DBS and extracted a 4 mm disk (Ø) from the centre of each spot by unilateral flow using 25 μl extraction solvent...
May 29, 2017: Journal of Mass Spectrometry: JMS
https://www.readbyqxmd.com/read/28553123/the-hiv-protease-inhibitor-nelfinavir-as-a-novel-therapeutic-approach-for-the-treatment-of-refractory-pediatric-leukemia
#9
Vanessa Meier-Stephenson, Justin Riemer, Aru Narendran
PURPOSE: Refractory pediatric leukemia remains one of the leading causes of death in children. Intensification of current chemotherapy regimens to improve the outcome in these children is often limited by the effects of drug resistance and cumulative toxicity. Hence, the search for newer agents and novel therapeutic approaches are urgently needed to formulate the next-generation early-phase clinical trials for these patients. MATERIALS AND METHODS: A comprehensive library of antimicrobials, including eight HIV protease inhibitors (nelfinavir [NFV], saquinavir, indinavir, ritonavir, amprenavir, atazanavir, lopinavir, and darunavir), was tested against a panel of pediatric leukemia cells by in vitro growth inhibition studies...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28532134/assessing-the-efficacy-of-second-line-antiretroviral-treatment-for-hiv-patients-failing-first-line-antiretroviral-therapy-in-iran-a-cohort-study
#10
Mehrnaz Rasooli-Nejad, Maryam Khazaee-Pool, Ladan Abbasian, Zahra Bayat Jozani, Sara Ahsani-Nasab, Banafsheh Moradmand Badie, Afsaneh Pargar, Gholamreza Esmaeeli Djavid
There are limited documents about HIV patients switched to second-line antiretroviral therapy (ART) in resource-limited countries. We aimed to assess the efficacy of second-line ART for HIV patients following first-line ART failure. This was a cohort study of HIV/AIDS patients with first-line ART treatment failure switched to second-line ART between January 2004 and March 2014, who followed for at least 12 months after switching. Fifty of studied patients (85%) were treated with regimens containing lopinavir/ritonavir (Kaletra) and nine of them (15%) treated with other regimes...
April 2017: Acta Medica Iranica
https://www.readbyqxmd.com/read/28528404/a-direct-comparison-of-the-effects-of-the-antiretroviral-drugs-stavudine-tenofovir-and-the-combination-lopinavir-ritonavir-on-bone-metabolism-in-a-rat-model
#11
M M Conradie, M van de Vyver, E Andrag, M Conradie, W F Ferris
Antiretroviral (ARV) treatment may induce metabolic complications in HIV patients on long-term therapy that can affect bone health. In this study, the effects of the ARVs Stavudine (d4T), Tenofovir (TDF) and Lopinavir/ritonavir (LPV/r) on bone metabolism and lipodystrophy were directly compared in rats to negate the consequences of HIV-associated confounding factors. Healthy 12-14-week-old male Wistar rats (n = 40) were divided into four treatment groups and received an oral animal equivalent dose of either Stavudine (6...
May 20, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/28499879/developing-a-flexible-pediatric-dosage-form-for-antiretroviral-therapy-a-fast-dissolving-tablet
#12
Manjari Lal, Manshun Lai, Marcus Estrada, Changcheng Zhu
Current presentations of the anti-HIV drugs lopinavir and ritonavir make appropriate dosing for children difficult. We conducted a feasibility study to develop a formulation for these drugs with child-safe excipients in a flexible dosage form for children across the pediatric age spectrum. The freeze-drying in blister approach was used to produce fast-dissolving tablets (FDTs), as these can be dispersed in fluids for easy administration, even to infants, and appropriate portions of the dispersion can be given for different ages/weights...
May 10, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28495562/nucleoside-reverse-transcriptase-inhibitor-cross-resistance-and-outcomes-from-second-line-antiretroviral-therapy-in-the-public-health-approach-an-observational-analysis-within-the-randomised-open-label-earnest-trial
#13
Nicholas I Paton, Cissy Kityo, Jennifer Thompson, Immaculate Nankya, Leonard Bagenda, Anne Hoppe, James Hakim, Andrew Kambugu, Joep J van Oosterhout, Mary Kiconco, Silvia Bertagnolio, Philippa J Easterbrook, Peter Mugyenyi, A Sarah Walker
BACKGROUND: Cross-resistance after first-line antiretroviral therapy (ART) failure is expected to impair activity of nucleoside reverse-transcriptase inhibitors (NRTIs) in second-line therapy for patients with HIV, but evidence for the effect of cross-resistance on virological outcomes is limited. We aimed to assess the association between the activity, predicted by resistance testing, of the NRTIs used in second-line therapy and treatment outcomes for patients infected with HIV. METHODS: We did an observational analysis of additional data from a published open-label, randomised trial of second-line ART (EARNEST) in sub-Saharan Africa...
May 8, 2017: Lancet HIV
https://www.readbyqxmd.com/read/28489856/randomized-trial-of-stopping-or-continuing-art-among-postpartum-women-with-pre-art-cd4-%C3%A2-400-cells-mm3
#14
Judith S Currier, Paula Britto, Risa M Hoffman, Sean Brummel, Gaerolwe Masheto, Esau Joao, Breno Santos, Linda Aurpibul, Marcelo Losso, Marie F Pierre, Adriana Weinberg, Devasena Gnanashanmugam, Nahida Chakhtoura, Karin Klingman, Renee Browning, Anne Coletti, Lynne Mofenson, David Shapiro, Jose Pilotto
BACKGROUND: Health benefits of postpartum antiretroviral therapy (ART) for human immunodeficiency virus (HIV) positive women with high CD4+ T-counts have not been assessed in randomized trials. METHODS: Asymptomatic, HIV-positive, non-breastfeeding women with pre-ART CD4+ T-cell counts ≥ 400 cells/mm3 started on ART during pregnancy were randomized up to 42 days after delivery to continue or discontinue ART. Lopinavir/ritonavir plus tenofovir/emtricitabine was the preferred ART regimen...
2017: PloS One
https://www.readbyqxmd.com/read/28486519/changes-in-body-mass-index-and-hemoglobin-concentration-in-breastfeeding-women-living-with-hiv-with-a-cd4-count-over-350-results-from-4-african-countries-the-anrs-12174-trial
#15
Eric Nagaonlé Somé, Ingunn M S Engebretsen, Nicolas Nagot, Nicolas Y Meda, Roselyne Vallo, Chipepo Kankasa, James K Tumwine, Mandisa Singata, Justus G Hofmeyr, Philippe Van de Perre, Thorkild Tylleskär
INTRODUCTION: Breastfeeding is recommended for infants born to HIV-infected women in low-income settings. Both breastfeeding and HIV-infection are energy demanding. Our objective was to explore how exclusive and predominant breastfeeding changes body mass index (BMI) among breastfeeding HIV1-positive women participating in the ANRS12174 trial (clinical trial no NCT0064026). METHODS: HIV-positive women (n = 1 267) with CD4 count >350, intending to breastfeed HIV-negative infants were enrolled from Burkina Faso, South Africa, Uganda and Zambia and counselled on breastfeeding...
2017: PloS One
https://www.readbyqxmd.com/read/28481997/patterns-of-growth-body-composition-and-lipid-profiles-in-a-south-african-cohort-of-human-immunodeficiency-virus-infected-and-uninfected-children-a-cross-sectional-study
#16
Sarah M Ramteke, Stephanie Shiau, Marc Foca, Renate Strehlau, Francoise Pinillos, Faeezah Patel, Avy Violari, Afaaf Liberty, Ashraf Coovadia, Louise Kuhn, Stephen M Arpadi
Background.: Prior research in sub-Saharan Africa reports dyslipidemia in perinatally human immunodeficiency virus (HIV)-infected children receiving ritonavir-boosted lopinavir (LPV/r) compared with efavirenz; however, interpretation of findings is limited by lack of comparison data from HIV-uninfected children. Methods.: We conducted a cross-sectional analysis of lipid profiles and growth within a larger longitudinal cohort study of perinatally HIV-infected and HIV-uninfected children aged 4-9 years in Johannesburg, South Africa...
May 6, 2017: Journal of the Pediatric Infectious Diseases Society
https://www.readbyqxmd.com/read/28480762/steady-state-pharmacokinetics-of-tenofovir-disoproxil-fumarate-in-human-immunodeficiency-virus-infected-chinese-patients
#17
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. 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...
July 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28475554/sustained-viral-suppression-in-hiv-infected-children-on-once-daily-lopinavir-ritonavir-in-clinical-practice
#18
Ivar P E Gondrie, Diane E T Bastiaans, Pieter L A Fraaij, Gertjan J A Driessen, Linda C Van Der Knaap, Eline G Visser, Petronette Van Jaarsveld, Ronald de Groot, Nico G Hartwig, David M Burger, Annemarie M C Van Rossum
BACKGROUND: The use of lopinavir/ritonavir once-daily (LPV/r QD) has not been approved for children. Good short-term clinical, virological and immunological outcomes have been observed in children on LPV/r QD. METHODS: We evaluated the long-term effectiveness of a LPV/r QD containing regimen in HIV-1 infected children in clinical practice. Selected children (aged 0-18 years) with an undetectable HIV-1 RNA viral load (<50 copies/mL) for at least 6 months on a twice-daily (BID) LPV/r-containing regimen switched to LPV/r QD...
May 4, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28463882/impact-of-intensified-antiretroviral-therapy-during-early-hiv-infection-on-gut-immunology-and-inflammatory-blood-biomarkers-a-randomized-controlled-trial
#19
Connie J Kim, Rodney Rousseau, Sanja Huibner, Colin Kovacs, Erika Benko, Kamnoosh Shahabi, Gabor Kandel, Mario Ostrowski, Rupert Kaul
OBJECTIVE: Standard antiretroviral therapy (ART) is slow to reverse gut mucosal immune defects that cause persistent inflammation and immune activation. We examined whether intensifying early-administered ART through the addition of maraviroc and raltegravir would accelerate their resolution. DESIGN: ART-naïve men with early HIV infection were randomized in a double-blind manner to receive ART (emtricitabine/tenofovir disoproxil fumarate + lopinavir/ritonavir), together with either combined raltegravir/maraviroc or placebo, for 48 weeks...
May 1, 2017: AIDS
https://www.readbyqxmd.com/read/28458904/fluticasone-furoate-induced-iatrogenic-cushing-syndrome-in-a-pediatric-patient-receiving-anti-retroviral-therapy
#20
S A A van den Berg, N E van 't Veer, J M A Emmen, R H T van Beek
SUMMARY: We present a case of iatrogenic Cushing's syndrome, induced by treatment with fluticasone furoate (1-2 dd, 27.5 µg in each nostril) in a pediatric patient treated for congenital HIV. The pediatric patient described in this case report is a young girl of African descent, treated for congenital HIV with a combination therapy of Lopinavir/Ritonavir (1 dd 320/80 mg), Lamivudine (1 dd 160 mg) and Abacavir (1 dd 320 mg). Our pediatric patient presented with typical Cushingoid features (i...
2017: Endocrinology, Diabetes & Metabolism Case Reports
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