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https://www.readbyqxmd.com/read/28099191/long-acting-combination-anti-hiv-drug-suspension-enhances-and-sustains-higher-drug-levels-in-lymph-node-cells-than-in-blood-cells-and-plasma
#1
John C Kraft, Lisa A McConnachie, Josefin Koehn, Loren Kinman, Carol Collins, Danny D Shen, Ann C Collier, Rodney J Y Ho
OBJECTIVE: To determine if a combination of anti-HIV drugs-tenofovir (TFV), lopinavir (LPV), and ritonavir (RTV)-in a lipid-stabilized nanosuspension (called TLC-ART101) could enhance and sustain intracellular drug levels and exposures in lymph node and blood cells above those in plasma. DESIGN: Four macaques were given a single dose of TLC-ART101 subcutaneously. Drug concentrations in plasma and mononuclear cells of the blood (PBMCs) and lymph nodes (LNMCs) were analyzed using a validated combination LC-MS/MS assay...
January 17, 2017: AIDS
https://www.readbyqxmd.com/read/28038962/confirming-model-predicted-pharmacokinetic-interactions-between-bedaquiline-and-lopinavir-ritonavir-or-nevirapine-in-patients-with-hiv-and-drug-resistant-tuberculosis
#2
Margreke J E Brill, Elin M Svensson, Mishal Pandie, Gary Maartens, Mats O Karlsson
Bedaquiline and its metabolite M2 are metabolised by CYP3A4. The antiretrovirals ritonavir-boosted lopinavir (LPV/r) and nevirapine inhibit and induce CYP3A4, respectively. Here we aimed to quantify nevirapine and LPV/r drug-drug interaction effects on bedaquiline and M2 in patients co-infected with HIV and multidrug-resistant tuberculosis (MDR-TB) using population pharmacokinetic (PK) analysis and compare these with model-based predictions from single-dose studies in subjects without TB. An observational PK study was performed in three groups of MDR-TB patients during bedaquiline maintenance dosing: HIV-seronegative patients (n = 17); and HIV-infected patients using antiretroviral therapy including nevirapine (n = 17) or LPV/r (n = 14)...
December 14, 2016: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/27936233/malaria-in-hiv-infected-children-receiving-hiv-protease-inhibitor-compared-with-non-nucleoside-reverse-transcriptase-inhibitor-based-antiretroviral-therapy-impaact-p1068s-substudy-to-p1060
#3
Charlotte V Hobbs, Erin E Gabriel, Portia Kamthunzi, Gerald Tegha, Jean Tauzie, Elizabeth Petzold, Linda Barlow-Mosha, Benjamin H Chi, Yonghua Li, Tiina Ilmet, Brian Kirmse, Jillian Neal, Sunil Parikh, Nagamah Deygoo, Patrick Jean Philippe, Lynne Mofenson, William Prescott, Jingyang Chen, Philippa Musoke, Paul Palumbo, Patrick E Duffy, William Borkowsky
BACKGROUND: HIV and malaria geographically overlap. HIV protease inhibitors kill malaria parasites in vitro and in vivo, but further evaluation in clinical studies is needed. METHODS: Thirty-one children from Malawi aged 4-62 months were followed every 3 months and at intercurrent illness visits for ≤47 months (September 2009-December 2011). We compared malaria parasite carriage by blood smear microscopy (BS) and confirmed clinical malaria incidence (CCM, or positive BS with malaria symptoms) in children initiated on HIV antiretroviral therapy (ART) with zidovudine, lamivudine, and either nevirapine (NVP), a non-nucleoside reverse transcriptase inhibitor, or lopinavir-ritonavir (LPV-rtv), a protease inhibitor...
2016: PloS One
https://www.readbyqxmd.com/read/27935971/costs-of-care-of-hiv-infected-children-initiating-lopinavir-ritonavir-based-antiretroviral-therapy-before-the-age-of-two-in-cote-d-ivoire
#4
Sophie Desmonde, Divine Avit, Junie Petit, Madeleine Amorissani Folquet, Francois Tanoh Eboua, Clarisse Amani Bosse, Evelyne Dainguy, Véronique Mea, Marguerite Timite-Konan, Sylvie Ngbeché, Andrea Ciaranello, Valeriane Leroy
OBJECTIVES: To access the costs of care for Ivoirian children before and after initiating LPV/r-based antiretroviral therapy (ART) before the age of two. METHODS: We assessed the direct costs of care for all HIV-infected children over the first 12 months on LPV/r-based ART initiated <2 years of age in Abidjan. We recorded all drug prescriptions, ART and cotrimoxazole prophylaxis delivery, medical analyses/examinations and hospital admissions. We compared these costs to those accrued in the month prior to ART initiation...
2016: PloS One
https://www.readbyqxmd.com/read/27925066/dioctophyme-renale-nematoda-enoplida-in-domestic-dogs-and-cats-in-the-extreme-south-of-brazil
#5
Josaine Cristina da Silva Rappeti, Carolina Siqueira Mascarenhas, Soliane Carra Perera, Gertrud Müller, Fabiane Borelli Grecco, Luísa Mariano Cerqueira da Silva, Carolina da Fonseca Sapin, Stella Falkenberg Rausch, Marlete Brum Cleff
Dioctophyme renale is a zoonotic nematode that parasites the kidneys of wild and domestic carnivores, and it has been reported frequently in Brazil. The aim here was to register the number of cases of dogs and cats diagnosed with dioctophymosis by necropsy (1981 to 2014) and ultrasound examination (2010 to 2015) in Pelotas-RS. In this context, a survey was conducted on dioctophymosis cases diagnosed at the Veterinary Pathology Laboratory (LPV) and Veterinary Clinical Hospital (HCV) of the Federal University of Pelotas (UFPel), and at a specialist veterinary imaging diagnostics clinic...
December 1, 2016: Revista Brasileira de Parasitologia Veterinária, Brazilian Journal of Veterinary Parasitology
https://www.readbyqxmd.com/read/27925025/initiatives-to-challenge-patent-barriers-and-their-relationship-with-the-price-of-medicines-procured-by-the-brazilian-unified-national-health-system
#6
Carolinne Thays Scopel, Gabriela Costa Chaves
Since 1996, when antiretroviral (ARV) treatments started being guaranteed to people living with HIV in Brazil, the government has faced the challenge of ensuring sustainability of this policy within a context of incorporating patented medicines. This article sought to analyze the historical series of the price of lopinavir/ritonavir (LPV/r) in Brazil and in the international market also considering the initiatives to challenge patent barriers between 2001 and 2012. The methods used were mapping initiatives to challenge LPV/r patent barriers and the analysis of historical series of its price in Brazil and in the international market...
December 1, 2016: Cadernos de Saúde Pública
https://www.readbyqxmd.com/read/27906013/combination-of-long-acting-hiv-fusion-inhibitor-albuvirtide-and-lpv-r-showed-potent-efficacy-in-hiv-1-patients
#7
Hongwei Zhang, Ronghua Jin, Cheng Yao, Tong Zhang, Meixia Wang, Wei Xia, Haiyan Peng, Xiaojuan Wang, Rongjian Lu, Changjin Wang, Dong Xie, Hao Wu
BACKGROUND: Long acting antiretroviral drugs represent a promising approach for chronic treatment of HIV infection. Here, we study the efficacy and safety of albuvirtide (ABT), an HIV-1 fusion inhibitor with a half life of 11-12 days in human. METHODS: ABT was evaluated in a 7-week, open-label and randomized trial, combining with LPV/r. Twenty HIV-1-infected adults were assigned to two dose groups, receiving ABT (160 or 320 mg) given weekly and LPV/r given twice daily...
February 10, 2016: AIDS Research and Therapy
https://www.readbyqxmd.com/read/27900210/a-new-lpv-modeling-approach-using-pca-based-parameter-set-mapping-to-design-a-pss
#8
Mohammad B Abolhasani Jabali, Mohammad H Kazemi
This paper presents a new methodology for the modeling and control of power systems based on an uncertain polytopic linear parameter-varying (LPV) approach using parameter set mapping with principle component analysis (PCA). An LPV representation of the power system dynamics is generated by linearization of its differential-algebraic equations about the transient operating points for some given specific faults containing the system nonlinear properties. The time response of the output signal in the transient state plays the role of the scheduling signal that is used to construct the LPV model...
January 2017: Journal of Advanced Research
https://www.readbyqxmd.com/read/27895016/are-prophylactic-and-therapeutic-target-concentrations-different-the-case-of-lopinavir-ritonavir-or-lamivudine-administered-to-infants-for-the-prevention-of-mother-to-child-hiv-1-transmission-during-breastfeeding
#9
Frantz Foissac, Jörn Blume, Jean-Marc Tréluyer, Thorkild Tylleskär, Chipepo Kankasa, Nicolas Meda, James K Tumwine, Mandisa Singata-Madliki, Kim Harper, Silvia M Illamola, Naïm Bouazza, Nicolas Nagot, Philippe Van de Perre, Stéphane Blanche, Déborah Hirt
The ANRS 12174 trial assessed the efficacy and tolerance of LPV/r versus 3TC prophylaxis administered to breastfed infants, whose HIV-infected mothers were not on ART. In this sub-study, we assessed LPV/r and 3TC pharmacokinetics to evaluate the percentage of infants with therapeutic plasma concentrations and to discuss these data in the context of a prophylactic treatment. Infants from the South African trial site underwent blood sampling for pharmacokinetic study at week 6, 26 and 38 of life. We applied a Bayesian approach to derive the 3TC and LPV pharmacokinetic parameters based on previously published pharmacokinetic models for HIV-infected children...
November 28, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27888600/-darunavir-cobicistat-monotherapy-experience-in-a-tertiary-hospital
#10
L Yunquera-Romero, R Asensi-Díez, J C Del Rio-Valencia, I Muñoz-Castillo, M A Castaño-Carracedo
OBJECTIVE: Ritonavir-boosted protease inhibitor (IP/r) monotherapy: darunavir/ritonavir (DRV/r) or lopinavir/ritonavir (LPV/r) monotherapy is only provided in the major treatment guidelines in pretreated patients to prevent toxicity associated with nucleoside/nucleotide reverse transcriptase inhibitor (NRTI), reduce costs and simplify antiretroviral treatment. To start IP/r monotherapy, according to GESIDA guidelines 2016, patients need to meet the following criteria: absence of chronic hepatitis B, plasma viral load <50 copies/ mL for at least 6 months and absence of protease inhibitors mutations or previous virologic failures to IP/r...
December 2016: Revista Española de Quimioterapia: Publicación Oficial de la Sociedad Española de Quimioterapia
https://www.readbyqxmd.com/read/27842440/caregiver-reported-antiretroviral-therapy-non-adherence-during-the-first-week-and-after-a-month-of-treatment-initiation-among-children-diagnosed-with-hiv-in-ethiopia
#11
Mulatu Biru, Degu Jerene, Pia Lundqvist, Mitikie Molla, Workeabeba Abebe, Inger Hallström
To achieve optimal virologic suppression for children undergoing antiretroviral therapy (ART), adherence must be excellent. This is defined as taking more than 95% of their prescribed doses. To our knowledge, no study in Ethiopia has evaluated the level of treatment adherence at the beginning of the child's treatment. Our aim was therefore to evaluate caregiver-reported ART non-adherence among children and any predictors for this during the early course of treatment. We conducted a prospective cohort study of 306 children with HIV in eight health facilities in Ethiopia who were registered at ART clinics between 20 December 2014 and 20 April 2015...
November 14, 2016: AIDS Care
https://www.readbyqxmd.com/read/27798431/hemeoxygenase-1-as-a-novel-driver-in-ritonavir-induced-insulin-resistance-in-hiv-1-infected-patients
#12
Ninon Taylor, Iris Kremser, Simon Auer, Gregor Hoermann, Richard Greil, Elisabeth Haschke-Becher, Harald Esterbauer, Lukas Kenner, Hannes Oberkofler
BACKGROUND: Hemeoxygenase-1 (HO-1) has recently been identified as a major driver of metaflammation and obesity-related insulin resistance (IR). Drug-induced IR increases cardiovascular risk within the HIV-1-infected population receiving antiretroviral therapy (ART). We therefore investigated a possible role of HO-1 in ART-induced IR. METHODS: Effects of HIV-1 protease inhibitor ritonavir and integrase inhibitor raltegravir on expression levels of HO-1 and proinflammatory cytokines including interleukin-1β (IL-1β), IL-6, IL-8, tumor necrosis factor-α (TNFα), Chemokine (C-C motif) ligand 5 (CCL5) and monocyte chemotactic protein 1 (MCP-1) were studied in monocyte and hepatocyte cell lines...
October 27, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/27749514/therapeutic-drug-monitoring-of-lopinavir-in-hiv-infected-children-on-second-line-antiretroviral-therapy-in-asia
#13
Linda Aurpibul, Sirinya Teerananchai, Wasana Prasitsuebsai, Tavitiya Sudjaritruk, Pope Kosalaraksa, Nia Kurniati, Khanh Huu Truong, Viet Chau Do, Lam Van Nguyen, Kulkanya Chokephaibulkit, Thida Singtoroj, Stephen J Kerr
BACKGROUND: Failure rates of second-line boosted protease inhibitor antiretroviral therapy regimens in children rise over time. Therapeutic drug monitoring can contribute to assessments of adherence. The authors assessed the performance characteristics of the US DHHS-recommended lopinavir (LPV) concentration of 1.0 mg/L for predicting virologic failure (VF) and intermediate- to high-level LPV resistance in Asian children. METHODS: LPV concentration, HIV RNA level, and adherence data from study participants in Thailand, Vietnam, and Indonesia receiving second-line LPV-based ART and followed for ≥24 weeks were analyzed...
December 2016: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/27740537/hyperlipidaemia-in-hiv-infected-patients-on-lopinavir-ritonavir-monotherapy-in-resource-limited-settings
#14
Mitch M Matoga, Mina C Hosseinipour, Evgenia Aga, Heather J Ribaudo, Nagalingeswaran Kumarasamy, John Bartlett, Michael D Hughes
BACKGROUND: Cardiovascular disease (CVD) is an emerging concern for HIV-infected patients. Hyperlipidemia is a risk factor for CVD and a complication of protease-inhibitor-based antiretroviral therapy, but little is known about its incidence and risk factors in treated patients in resource-limited settings (RLS). METHODS: We conducted a secondary analysis of ACTG A5230 trial in which HIV-infected adults from India, Malawi, Tanzania, Thailand and South Africa, with virologic relapse on first line therapy were initiated on lopinavir/ritonavir (LPV/r) monotherapy...
October 14, 2016: Antiviral Therapy
https://www.readbyqxmd.com/read/27736953/projected-uptake-of-new-antiretroviral-arv-medicines-in-adults-in-low-and-middle-income-countries-a-forecast-analysis-2015-2025
#15
Aastha Gupta, Sandeep Juneja, Marco Vitoria, Vincent Habiyambere, Boniface Dongmo Nguimfack, Meg Doherty, Daniel Low-Beer
With anti-retroviral treatment (ART) scale-up set to continue over the next few years it is of key importance that manufacturers and planners in low- and middle-income countries (LMICs) hardest hit by the HIV/AIDS pandemic are able to anticipate and respond to future changes to treatment regimens, generics pipeline and demand, in order to secure continued access to all ARV medicines required. We did a forecast analysis, using secondary WHO and UNAIDS data sources, to estimate the number of people living with HIV (PLHIV) and the market share and demand for a range of new and existing ARV drugs in LMICs up to 2025...
2016: PloS One
https://www.readbyqxmd.com/read/27708251/an-open-label-randomized-study-of-the-impact-on-insulin-sensitivity-lipid-profile-and-vascular-inflammation-by-treatment-with-lopinavir-ritonavir-or-raltegravir-in-hiv-negative-male-volunteers
#16
Paul Randell, Akil Jackson, Ana Milinkovic, Marta Boffito, Graeme Moyle
BACKGROUND: We aimed to measure the effect of raltegravir (RAL) on insulin sensitivity and surrogates of CV risk in healthy HIV-seronegative volunteers compared to that of lopinavir/r (LPV/r), a positive control. METHODS: An open label, two phase crossover study in HIV-negative male subjects randomized 1:1 to receive either 2 weeks of LPV/r followed by a two week washout period and two weeks of RAL, or RAL initially followed by LPV/r. A hyperinsulinaemic euglycaemic clamp was performed prior to and following each 2-week dosing phase...
October 6, 2016: Antiviral Therapy
https://www.readbyqxmd.com/read/27705950/evolution-of-renal-function-in-african-patients-initiating-second-line-antiretroviral-treatment-findings-from-the-2lady-anrs-12169-trial
#17
Amandine Cournil, Arsène Hema, Sabrina Eymard-Duvernay, Laura Ciaffi, Stéphanie Badiou, Firmin N Kabore, Assane Diouf, Liliane Ayangma, Vincent Le Moing, Jacques Reynes, Sinata Koulla-Shiro, Eric Delaporte
BACKGROUND: To investigate change in renal function in African patients initiating second line ART including ritonavir-boosted protease inhibitor (PI/r) with or without tenofovir disoproxil fumarate (TDF). METHODS: HIV-1 positive adults, failing standard first line ART were randomized to either TDF/FTC+LPV/r; ABC+ddI+LPV/r or TDF/FTC+DRV/r and followed until 18 months. Patients with an estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1,73m(2) at baseline were included in this analysis...
October 5, 2016: Antiviral Therapy
https://www.readbyqxmd.com/read/27704010/human-immunodeficiency-virus-1-sequence-changes-and-drug-resistance-mutation-among-virologic-failures-of-lopinavir-ritonavir-monotherapy-aids-clinical-trials-group-protocol-a5230
#18
Saran Vardhanabhuti, David Katzenstein, John Bartlett, Nagalingeswaran Kumarasamy, Carole L Wallis
Background.  The mechanism of virologic failure (VF) of lopinavir/ritonavir (LPV/r) monotherapy is not well understood. We assessed sequence changes in human immunodeficiency virus-1 reverse-transcriptase (RT) and protease (PR) regions. Methods.  Human immunodeficiency virus-1 pol sequences from 34 participants who failed second-line LPV/r monotherapy were obtained at study entry (SE) and VF. Sequence changes were evaluated using phylogenetic analysis and hamming distance. Results.  Human immunodeficiency virus-1 sequence change was higher over drug resistance mutation (DRM) sites (median genetic distance, 2...
September 2016: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/27586019/qbd-based-development-of-proliposome-of-lopinavir-for-improved-oral-bioavailability
#19
Grishma M Patel, Pragna K Shelat, Anita N Lalwani
Aim of present work was to apply Quality by Design (QbD) principles for the development of proliposome of poorly soluble lopinavir (LPV). The patient-centric quality target product profile (QTPP) was defined and critical quality attributes (CQAs) earmarked. Risk assessment studies were carried out to identify the probable risks affecting the CQAs of the product. On the basis of preliminary study, lipid: drug ratio and amount of carrier were selected as critical material attributes (CMAs) and were optimized by face centered central composite design...
August 29, 2016: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27579612/dyslipidemias-and-elevated-cardiovascular-risk-on-lopinavir-based-antiretroviral-therapy-in-cambodia
#20
Setha Limsreng, Olivier Marcy, Sowath Ly, Vara Ouk, Hak Chanroeurn, Saem Thavary, Ban Boroath, Ana Canestri, Gérald Viretto, Jean-François Delfraissy, Olivier Ségéral
BACKGROUND: Lopinavir/ritonavir (LPV/r) is widely used in Cambodia with high efficacy but scarce data exist on long-term metabolic toxicity. METHODS: We carried out a cross-sectional and retrospective study evaluating metabolic disorders and cardiovascular risk in Cambodian patients on LPV/r-based antiretroviral therapy (ART) for > 1 year followed in Calmette Hospital, Phnom Penh. Data collected included cardiovascular risk factors, fasting blood lipids and glucose, and retrospective collection of bioclinical data...
2016: PloS One
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