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https://www.readbyqxmd.com/read/28805110/lack-of-interaction-of-lopinavir-solid-drug-nanoparticles-with-cells-of-the-immune-system
#1
Neill J Liptrott, Marco Giardiello, Tom O McDonald, Steven P Rannard, Andrew Owen
AIM: We previously demonstrated that solid drug nanoparticles (SDNs) lopinavir (LPV) dispersed into aqueous media display favorable pharmacokinetics. METHODS: The impact of LPV SDNs on the function and phenotype of primary human T cells and macrophages (primary sites of HIV replication) was investigated. RESULTS: LPV significantly increased IL-1β (ninefold higher than untreated cells; p = 0.045) and TNF-α (sixfold higher than untreated cells; p = 0...
August 14, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28800382/suboptimal-cotrimoxazole-prophylactic-concentrations-in-hiv-infected-children-according-to-the-who-guidelines
#2
C Pressiat, V Mea-Assande, C Yonaba, J-M Treluyer, D-L Dahourou, M Amorissani-Folquet, S Blanche, F Eboua, D Ye, G Lui, K Malateste, Y Zheng, V Leroy, D Hirt
AIMS: A clinical study was conduct in HIV-infected children to evaluate the prophylactic doses of cotrimoxazole (sulfamethoxazole (SMX) and trimethoprim (TMP)) advised by WHO. METHODS: Children received lopinavir-based antiretroviral therapy with cotrimoxazole prophylaxis (200 mg of SMX/ 40 mg of TMP once daily). Nonlinear mixed effects modelling approach was used to analyze plasma concentrations. Factors that could impact the pharmacokinetic profile were investigate...
August 11, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28797181/hiv-resistance-with-correlation-to-pmtct-regimen-in-hiv-infected-infants-in-northern-tanzania
#3
Dorothy Elizabeth Dow, Werner Schimana, Balthazar M Nyombi, Blandina T Mmbaga, Aisa M Shayo, John A Bartlett, Charles G Massambu, Emmanuel G Kifaro, Elizabeth L Turner, Todd DeMarco, Fangping Cai, Coleen Cunningham, Ann M Buchanan
Prevention of mother-to-child transmission (PMTCT) guidelines recommend that all HIV-infected pregnant woman receive antiretroviral therapy (Option B) and HIV-infected infants should initiate therapy with a protease inhibitor based regimen; however, implementation of these guidelines has lagged in many resource-limited settings. Tanzania only recently implemented these guidelines with little country specific data to inform whether HIV non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance was present among infected infants under the Option A guidelines...
August 11, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28783807/comparative-safety-of-antiretroviral-treatment-regimens-in-pregnancy
#4
Rebecca Zash, Denise L Jacobson, Modiegi Diseko, Gloria Mayondi, Mompati Mmalane, Max Essex, Chipo Petlo, Shahin Lockman, Joseph Makhema, Roger L Shapiro
Importance: Maternal antiretroviral treatment (ART) started before conception may increase the risk for adverse birth outcomes among women with human immunodeficiency virus (HIV) infection, but whether the risk differs by ART regimen is unknown. Objective: To compare the risk for selected birth outcomes by maternal ART regimen. Design, Setting, and Participants: This observational birth outcomes surveillance study compared all live births and stillbirths with a gestational age of at least 24 weeks in 8 geographically dispersed government hospitals throughout Botswana (approximately 45% of births nationwide)...
August 7, 2017: JAMA Pediatrics
https://www.readbyqxmd.com/read/28770596/high-rates-of-viral-suppression-in-adults-and-children-with-high-cd4-counts-using-a-streamlined-art-delivery-model-in-the-search-trial-in-rural-uganda-and-kenya
#5
Dalsone Kwarisiima, Moses R Kamya, Asiphas Owaraganise, Florence Mwangwa, Dathan M Byonanebye, James Ayieko, Albert Plenty, Doug Black, Tamara D Clark, Bridget Nzarubara, Katherine Snyman, Lillian Brown, Elizabeth Bukusi, Craig R Cohen, Elvin H Geng, Edwin D Charlebois, Theodore D Ruel, Maya L Petersen, Diane Havlir, Vivek Jain
INTRODUCTION: The 2015 WHO recommendation of antiretroviral therapy (ART) for all HIV-positive persons calls for treatment initiation in millions of persons newly eligible with high CD4+ counts. Efficient and effective care models are urgently needed for this population. We evaluated clinical outcomes of asymptomatic HIV-positive adults and children starting ART with high CD4+ counts using a novel streamlined care model in rural Uganda and Kenya. METHODS: In the 16 intervention communities of the HIV test-and-treat Sustainable East Africa Research for Community Health Study (NCT01864603), all HIV-positive individuals irrespective of CD4 were offered ART (efavirenz [EFV]/tenofovir disoproxil fumarate + emtricitabine (FTC) or lamivudine (3TC)...
July 21, 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/28764578/developments-in-early-diagnosis-and-therapy-of-hiv-infection-in-newborns
#6
Francisco Canals, Mar Masiá, Félix Gutiérrez
Infants who acquire HIV have an exceptionally high risk of morbidity and mortality if they do not receive antiretroviral therapy (ART). Areas covered: This review aims to summarize the currently available evidence on ART in HIV-infected neonates. Data were obtained from literature searches from PubMed, abstracts from International Conferences (2000-2017), and authors' files. Expert opinion: Current evidence favors early diagnosis and prompt ART of HIV infection in newborns. The precise timing of initiation of ART remains undetermined...
August 2, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28758024/serum-lipid-and-glucose-profiles-in-hiv-positive-nigerian-children
#7
EDITORIAL
Olukemi O Ige, Christopher S Yilgwan, Augustine O Ebonyi, Ruth Adah, Idris Adedeji, Esther S Yiltok, Stephen Oguche, Fidelia Bode-Thomas
OBJECTIVES: To describe the fasting serum lipid and glucose profiles of HIV-positive Nigerian children and determine the prevalence and risk factors for dyslipidaemia and hyperglycaemia, which are risk factors for cardiovascular diseases. METHODS: This was a comparative cross-sectional study carried out at the Paediatric Infectious Disease Clinic (PIDC) of the Jos University Teaching Hospital (JUTH) for HIV-positive children and at two primary schools in Jos for HIV-negative children as controls...
July 1, 2017: Journal of Virus Eradication
https://www.readbyqxmd.com/read/28753637/collaborative-update-of-a-rule-based-expert-system-for-hiv-1-genotypic-resistance-test-interpretation
#8
Roger Paredes, Philip L Tzou, Gert van Zyl, Geoff Barrow, Ricardo Camacho, Sergio Carmona, Philip M Grant, Ravindra K Gupta, Raph L Hamers, P Richard Harrigan, Michael R Jordan, Rami Kantor, David A Katzenstein, Daniel R Kuritzkes, Frank Maldarelli, Dan Otelea, Carole L Wallis, Jonathan M Schapiro, Robert W Shafer
INTRODUCTION: HIV-1 genotypic resistance test (GRT) interpretation systems (IS) require updates as new studies on HIV-1 drug resistance are published and as treatment guidelines evolve. METHODS: An expert panel was created to provide recommendations for the update of the Stanford HIV Drug Resistance Database (HIVDB) GRT-IS. The panel was polled on the ARVs to be included in a GRT report, and the drug-resistance interpretations associated with 160 drug-resistance mutation (DRM) pattern-ARV combinations...
2017: PloS One
https://www.readbyqxmd.com/read/28741965/cost-effectiveness-of-dolutegravir-abacavir-lamivudine-in-hiv-1-treatment-naive-tn-patients-in-france
#9
Gilles Pialoux, Anne-Geneviève Marcelin, Hélène Cawston, Caroline Guilmet, Laurent Finkielsztejn, Audrey Laurisse, Céline Aubin
BACKGROUND: To evaluate the cost-effectiveness of an integrase inhibitor (INI), dolutegravir (DTG), in combination with abacavir (ABC)/lamivudine (3TC) in France, in treatment-naive (TN) HIV adult patients. METHODS: The ARAMIS microsimulation Markov model, evaluates costs and effects of DTG vs. first-line ARVs options including INIs (raltegravir, elvitegravir/c), protease inhibitors (PIs) (darunavir/r, atazanavir/r, lopinavir/r), non-nucleoside reverse transcriptase inhibitors (efavirenz and rilpivirine)...
July 31, 2017: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/28718515/impact-of-single-nucleotide-polymorphisms-on-plasma-concentrations-of-efavirenz-and-lopinavir-ritonavir-in-chinese-children-infected-with-the-human-immunodeficiency-virus
#10
Xia Liu, Qing Ma, Yan Zhao, Weiwei Mu, Xin Sun, Yuewu Cheng, Huiping Zhang, Ye Ma, Fujie Zhang
Single-nucleotide polymorphisms (SNPs) in the genes that encode the cytochrome P450 (CYP) drug metabolizing enzymes and drug transporters have been reported to influence antiretroviral drug pharmacokinetics. While primarily metabolized by CYP2B6 and -3A, efavirenz (EFV) and lopinavir/ritonavir (LPV/r) are substrates of P-glycoprotein and solute carrier organic (SLCO) anion transporter, respectively OBJECTIVE: To investigate the association between SNPs and efavirenz (EFV) or lopinavir/ritonavir (LPV/r) concentrations in Chinese children infected with the human immunodeficiency virus (HIV) METHODS: Genotyping was performed on CYP2B6 516G→T, -1459C→T, and -983T→C, ABCB1 3435C→T, and SLCO1B1 521T→C in 229 HIV-infected Chinese pediatric patients with an age range from 4...
July 17, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28717974/improvement-of-oral-bioavailability-of-lopinavir-without-co-administration-of-ritonavir-using-microspheres-of-thiolated-xyloglucan
#11
Ashwini R Madgulkar, Mangesh R Bhalekar, Ashwini A Kadam
Lopinavir is a BCS Class IV drug exhibiting poor bioavailability due to P-gp efflux and limited permeation. The aim of this research was to formulate and characterize microspheres of lopinavir using thiolated xyloglucan (TH-MPs) as carrier to improve its oral bioavailability without co-administration of ritonavir. Thiomeric microspheres were prepared by ionotropic gelation between alginic acid and calcium ions. Interaction studies were performed using Fourier transform infrared spectroscopy (FT-IR). The thiomeric microspheres were characterized for its entrapment efficiency, T80, surface morphology, and mucoadhesion employing in vitro wash off test...
July 17, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28712942/structure-based-discovery-of-clinically-approved-drugs-as-zika-virus-ns2b-ns3-protease-inhibitors-that-potently-inhibit-zika-virus-infection-in%C3%A2-vitro-and-in%C3%A2-vivo
#12
Shuofeng Yuan, Jasper Fuk-Woo Chan, Helena den-Haan, Kenn Ka-Heng Chik, Anna Jinxia Zhang, Chris Chung-Sing Chan, Vincent Kwok-Man Poon, Cyril Chik-Yan Yip, Winger Wing-Nga Mak, Zheng Zhu, Zijiao Zou, Kah-Meng Tee, Jian-Piao Cai, Kwok-Hung Chan, Jorge de la Peña, Horacio Pérez-Sánchez, José Pedro Cerón-Carrasco, Kwok-Yung Yuen
Zika virus (ZIKV) infection may be associated with severe complications in fetuses and adults, but treatment options are limited. We performed an in silico structure-based screening of a large chemical library to identify potential ZIKV NS2B-NS3 protease inhibitors. Clinically approved drugs belonging to different drug classes were selected among the 100 primary hit compounds with the highest predicted binding affinities to ZIKV NS2B-NS3-protease for validation studies. ZIKV NS2B-NS3 protease inhibitory activity was validated in most of the selected drugs and in vitro anti-ZIKV activity was identified in two of them (novobiocin and lopinavir-ritonavir)...
July 14, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28686654/a-retrospective-case-cohort-study-comparing-treatment-outcomes-in-abacavir-versus-stavudine-containing-first-line-antiretroviral-treatment-regimens-in-children-3yrs-old-at-a-paediatric-programme-based-in-soweto-south-africa
#13
Haseena Cassim, Kennedy Otwombe, Erica Lazarus, Afaaf Liberty, Glenda E Gray, Oppel B W Greeff, Avy Violari
INTRODUCTION: The current World Health Organization guideline for first line antiretroviral therapy (ART) in HIV-infected children recommends the use of abacavir and lamivudine as nucleoside backbones and no longer includes stavudine. We compared treatment outcomes with abacavir (ABC) versus stavudine (d4T) in a cohort of HIV-1 infected children 6 and 12 months after antiretroviral therapy was initiated. METHODS: This was a retrospective case-cohort study, using programmatic data from children enrolled in the Paediatric Wellness Programme at the Perinatal HIV Research Unit in Soweto, South Africa between 2005 and 2013...
2017: PloS One
https://www.readbyqxmd.com/read/28676669/carfilzomib-resistance-due-to-abcb1-mdr1-overexpression-is-overcome-by-nelfinavir-and-lopinavir-in-multiple-myeloma
#14
A Besse, S C Stolze, L Rasche, N Weinhold, G J Morgan, M Kraus, J Bader, H S Overkleeft, L Besse, C Driessen
Proteasome inhibitor carfilzomib has activity superior to bortezomib and is increasingly incorporated in multiple myeloma (MM) frontline therapy and relapsed settings. Most MM patients ultimately experience proteasome inhibitor-refractory disease, an unmet medical need with poorly understood biology and dismal outcome. Pharmacologic targeting of ABCB1 improved patient outcomes, including MM, but suffered from adverse drug effects and insufficient plasma concentrations. Proteomics analysis identified ABCB1 overexpression as the most significant change in carfilzomib-resistant MM cells...
July 5, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28649306/decreasing-prevalence-of-transmitted-drug-resistance-among-art-naive-hiv-1-infected-patients-in-iceland-1996-2012
#15
Malik Sallam, Gülşen Özkaya Şahin, Hlynur Indriðason, Joakim Esbjörnsson, Arthur Löve, Anders Widell, Magnus Gottfreðsson, Patrik Medstrand
Introduction: Resistance to antiretroviral drugs can complicate the management of HIV-1 infection and impair control of its spread. The aim of the current study was to investigate the prevalence and transmission of HIV-1 drug resistance among 106 antiretroviral therapy (ART)-naïve patients diagnosed in Iceland (1996-2012). Methods: HIV-1 polymerase sequences were analysed using the Calibrated Population Resistance tool. Domestic spread of transmitted drug resistance (TDR) was investigated through maximum likelihood and Bayesian approaches...
2017: Infection Ecology & Epidemiology
https://www.readbyqxmd.com/read/28626835/disrupted-er-to-golgi-trafficking-underlies-anti-hiv-drugs-and-alcohol-induced-cellular-stress-and-hepatic-injury
#16
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
#17
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
#18
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
#19
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
#20
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
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