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Lisa A Mcconnachie, Loren M Kinman, Josefin Koehn, John C Kraft, Sarah Lane, Wonsok Lee, Ann C Collier, Rodney J Y Ho
Daily oral antiretroviral therapy (ART) regimens produce limited drug exposure in tissues where residual HIV persists, and suffer from poor patient adherence and disparate drug kinetics, which all negatively impact outcomes. To address this, we developed a tissue- and cell-targeted long-acting 4-in-1 nanosuspension composed of lopinavir (LPV), ritonavir (RTV), tenofovir (TFV), lamivudine (3TC). In four macaques dosed subcutaneously, drug levels over 5 weeks in plasma, lymph node, and peripheral blood mononuclear cells (LNMCs, PBMCs) were analyzed by LC-MS/MS...
March 13, 2018: Journal of Pharmaceutical Sciences
Maartje Dijkstra, Rik H W Van Lunsen, Katherine W Kooij, Udi Davidovich, Rosan A Van Zoest, Ferdinand W M N Wit, Maria Prins, Peter Reiss, Maarten F Schim Van Der Loeff
INTRODUCTION: HIV-1-infected men who have sex with men (MSM) more often experience sexual dysfunctions than the general population. We assessed associations between HIV-1 status and decreased sexual functioning among MSM. METHODS: We used cross-sectional data from 399 HIV-1-infected MSM mostly on combination antiretroviral therapy (cART) and 366 HIV-1-uninfected MSM aged ≥45 years participating in the AGEhIV Cohort Study. The study questionnaire included questions on erectile function, sexual satisfaction, and sexual desire...
March 15, 2018: AIDS
Neill J Liptrott, Marco Giardiello, Tom O McDonald, Steve P Rannard, Andrew Owen
BACKGROUND: Recent work has developed solid drug nanoparticles (SDNs) of efavirenz that have been demonstrated, preclinically, improved oral bioavailability and the potential to enable up to a 50% dose reduction, and is currently being studied in a healthy volunteer clinical trial. Other SDN formulations are being studied for parenteral administration, either as intramuscular long-acting formulations, or for direct administration intravenously. The interaction of nanoparticles with the immunological and haematological systems can be a major barrier to successful translation but has been understudied for SDN formulations...
March 15, 2018: Journal of Nanobiotechnology
Ovokeroye A Abafe, Jana Späth, Jerker Fick, Stina Jansson, Chris Buckley, Annegret Stark, Bjoern Pietruschka, Bice S Martincigh
South Africa has the largest occurrence of the human immune deficiency virus (HIV) in the world but has also implemented the largest antiretroviral (ARV) treatment programme. It was therefore of interest to determine the presence and concentrations of commonly used antiretroviral drugs (ARVDs) and, also, to determine the capabilities of wastewater treatment plants (WWTPs) for removing ARVDs. To this end, a surrogate standard based LC-MS/MS method was optimized and applied for the detection of thirteen ARVDs used in the treatment and management of HIV/acquired immune deficiency syndrome (HIV/AIDS) in two major and one modular WWTP in the eThekwini Municipality in KwaZulu-Natal, South Africa...
February 20, 2018: Chemosphere
Nico Holmstock, Marlies Oorts, Jan Snoeys, Pieter Annaert
Hepatic drug transporters play a pivotal role in the excretion of drugs from the body, in drug-drug interactions as well as in drug-induced liver toxicity. Hepatocytes cultured in sandwich configuration are an advantageous model to investigate the interactions of drug candidates with apical efflux transporters in a bio-relevant manner. However, the commonly used 'offline' assays (i.e. that rely on measuring intracellular accumulated amounts after cell lysis) are time and resource consuming while data output is often high and variable...
March 9, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Erik Mogalian, Luisa M Stamm, Anu Osinusi, Diana M Brainard, Gong Shen, Kah Hiing John Ling, Anita Mathias
Background: Combining antiviral regimens in the HCV/HIV coinfected population can be complex as they share overlapping mechanisms for elimination that may result in potential drug interactions. The pharmacokinetics, safety, and tolerability of concomitantly administered sofosbuvir/velpatasvir (SOF/VEL) with multiple commonly prescribed antiretroviral (ARV) regimens were evaluated. Methods: Healthy volunteers were enrolled into two phase 1, open-label, randomized, multiple-dose, cross-over studies...
March 7, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
(no author information available yet)
No abstract text is available yet for this article.
March 13, 2018: AIDS
Sanjay Pujari, Sunil Gaikwad, Vivek Bele, Kedar Joshi, Digamber Dabhade
BACKGROUND: There is no information on the clinical effectiveness of Maraviroc (MVC) amongst People Living with HIV (PLHIV) in India infected with HIV-1 Subtype C viruses. METHODS: We conducted a retrospective chart review of adult PLHIV on MVC based Antiretroviral (ARV) regimens for at least 6 months. Maraviroc was initiated amongst PLHIV with documented R5 tropic viruses (determined by in-house population sequencing of the V3 loop in triplicate and interpreted using the Geno2Pheno algorithm) in combination with an Optimized Background regimen (designed using genotypic resistance testing and past ARV history)...
January 2018: Journal of the International Association of Providers of AIDS Care
Nicole S Delino, Manabu Aoki, Hironori Hayashi, Shin-Ichiro Hattori, Simon B Chang, Yuki Takamatsu, Cuthbert D Martyr, Debananda Das, Arun K Ghosh, Hiroaki Mitsuya
We identified four novel nonpeptidic human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs), GRL-078, -079, -077, and -058, containing an alkylamine at the C5 position of P2-tetrahydropyrano-tetrahydrofuran (Tp-THF) and a P2' -cyclopropyl (Cp)(or isopropyl)-aminobenzothiazole (Abt). Their 50% effective concentrations (EC50 s) were 2.5-30 nM against wild-type HIV-1NL4-3 , 0.3-6.7 nM against HIV-2EHO , and 0.9-90 nM against laboratory-selected-PI-resistant HIV-1 and clinical HIV-1 variants resistant to multiple FDA-approved PIs (HIVMDR )...
February 20, 2018: Antimicrobial Agents and Chemotherapy
Zachary J Tabb, Blandina T Mmbaga, Monica Gandhi, Alexander Louie, Karen Kuncze, Hideaki Okochi, Aisa M Shayo, Elizabeth L Turner, Coleen K Cunningham, Dorothy E Dow
OBJECTIVE: We assessed the relationship of self-reported adherence versus antiretroviral therapy (ART) concentrations in hair with virologic outcomes among young people living with HIV. DESIGN: This was a cross-sectional study that enrolled young people living with HIV age 11-24 years, who attended a youth HIV clinic in Moshi, Tanzania. METHODS: ART adherence was assessed by self-report, drug concentration in hair samples, and plasma HIV-1 RNA measurements...
February 12, 2018: AIDS
Tomokazu Tanaka, Harumasa Nakazawa, Naohide Kuriyama, Masao Kaneki
Highly active antiretroviral therapy (HAART) has successfully reduced the mortality rate of patients with human immune deficiency virus (HIV) and HIV protease inhibitors (HIV PIs) are key components of HAART. Complications of HAART, particularly those associated with HIV PIs including lipodystrophy and metabolic disturbance, have emerged as an important public health issue. No specific treatment is available to prevent and/or treat HIV PI-associated lipodystrophy and metabolic syndrome. The present study demonstrated that a relatively low-dose of farnesyltransferase inhibitor (FTI), tipifarnib (3 mg/kg/day, subcutaneous injection) and lonafarnib (5 mg/kg/day, subcutaneous injection), prevented the onset of lipodystrophy and metabolic syndrome induced by the combination of two HIV PIs, lopinavir (50 mg/kg/day, intraperitoneal injection) and ritonavir (12...
February 2018: Experimental and Therapeutic Medicine
John C Kraft, Lisa A McConnachie, Josefin Koehn, Loren Kinman, Jianguo Sun, Ann C Collier, Carol Collins, Danny D Shen, Rodney J Y Ho
Existing oral antiretroviral (ARV) agents have been shown in human studies to exhibit limited lymph node penetration and lymphatic drug insufficiency. As lymph nodes are a reservoir of HIV, it is critical to deliver and sustain effective levels of ARV combinations in these tissues. To overcome lymph node drug insufficiency of oral combination ARV therapy (cART), we developed and reported a long-acting and lymphocyte-targeting injectable that contains three ARVs-hydrophobic lopinavir (LPV) and ritonavir (RTV), and hydrophilic tenofovir (TFV)-stabilized by lipid excipients in a nanosuspension...
February 9, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Julie Jesson, Désiré L Dahourou, Madeleine Amorissani Folquet, Karen Malateste, Caroline Yonaba, Marie-Sylvie N'Gbeche, Sylvie Ouédraogo, Véronique Mea-Assande, Clarisse Amani-Bossé, Stéphane Blanche, Marguerite Timité-Konan, Valériane Leroy
BACKGROUND: There is limited information about malnutrition, growth evolution and metabolic changes among children initiated early on lopinavir-based antiretroviral therapy (ART) in Africa. METHODS: HIV-1-infected children, age <2 years were initiated on ART, as part of the MONOD ANRS 12206 project, conducted in Burkina Faso and Côte d'Ivoire. Weight-for-age, height-for-age and weight-for-height Z-scores (WAZ, HAZ, WHZ) defined malnutrition (Z-score <-2 standard deviations [SD]) using WHO growth references...
February 3, 2018: Pediatric Infectious Disease Journal
J R Santos, A Cozzi-Lepri, A Phillips, S De Wit, C Pedersen, P Reiss, A Blaxhult, A Lazzarin, M Sluzhynska, C Orkin, C Duvivier, J Bogner, P Gargalianos-Kakolyris, P Schmid, G Hassoun, I Khromova, M Beniowski, V Hadziosmanovic, D Sedlacek, R Paredes, J D Lundgren
OBJECTIVES: The aim of the study was to evaluate the long-term response to antiretroviral treatment (ART) based on atazanavir/ritonavir (ATZ/r)-, darunavir/ritonavir (DRV/r)-, and lopinavir/ritonavir (LPV/r)-containing regimens. METHODS: Data were analysed for 5678 EuroSIDA-enrolled patients starting a DRV/r-, ATZ/r- or LPV/r-containing regimen between 1 January 2000 and 30 June 2013. Separate analyses were performed for the following subgroups of patients: (1) ART-naïve subjects (8%) at ritonavir-boosted protease inhibitor (PI/r) initiation; (2) ART-experienced individuals (44%) initiating the new PI/r with a viral load (VL) ≤500 HIV-1 RNA copies/mL; and (3) ART-experienced patients (48%) initiating the new PI/r with a VL >500 copies/mL...
February 1, 2018: HIV Medicine
Yaseen M Arabi, Adel Alothman, Hanan H Balkhy, Abdulaziz Al-Dawood, Sameera AlJohani, Shmeylan Al Harbi, Suleiman Kojan, Majed Al Jeraisy, Ahmad M Deeb, Abdullah M Assiri, Fahad Al-Hameed, Asim AlSaedi, Yasser Mandourah, Ghaleb A Almekhlafi, Nisreen Murad Sherbeeni, Fatehi Elnour Elzein, Javed Memon, Yusri Taha, Abdullah Almotairi, Khalid A Maghrabi, Ismael Qushmaq, Ali Al Bshabshe, Ayman Kharaba, Sarah Shalhoub, Jesna Jose, Robert A Fowler, Frederick G Hayden, Mohamed A Hussein
BACKGROUND: It had been more than 5 years since the first case of Middle East Respiratory Syndrome coronavirus infection (MERS-CoV) was recorded, but no specific treatment has been investigated in randomized clinical trials. Results from in vitro and animal studies suggest that a combination of lopinavir/ritonavir and interferon-β1b (IFN-β1b) may be effective against MERS-CoV. The aim of this study is to investigate the efficacy of treatment with a combination of lopinavir/ritonavir and recombinant IFN-β1b provided with standard supportive care, compared to treatment with placebo provided with standard supportive care in patients with laboratory-confirmed MERS requiring hospital admission...
January 30, 2018: Trials
Alicia Ramírez-Ramírez, Elías Sánchez-Serrano, Giselle Loaiza-Flores, Noemí Plazola-Camacho, Rosa Georgina Rodríguez-Delgado, Ricardo Figueroa-Damián, Mauricio Domínguez-Castro, Margarita López-Martínez, Zayra Flores-García, Jessica Hernández-Pineda
The primary strategy to avoid mother-to-child transmission of human immunodeficiency virus (HIV) through breastfeeding is administration of highly active antiretroviral therapy (HAART) to HIV-positive pregnant women. Because significant changes in the pharmacokinetics of antiretroviral (ARV) drugs occur during pregnancy, quantifying HAART and the viral load in breast milk in this population is essential. Here, we developed an analytical assay for the simultaneous quantification of four ARV drugs in breast milk using ultra-performance liquid chromatography coupled to tandem mass spectrometry...
2018: PloS One
Thiago S Torres, Linda J Harrison, Alberto M La Rosa, Sandra W Cardoso, Lu Zheng, McNeil Ngongondo, Fatma Some, Umesh G Lalloo, Thando Mwelase, Ann C Collier, Michael D Hughes
OBJECTIVE: We evaluated improvement of quality of life (QoL) after one year of second-line antiretroviral therapy (ART) use in resource-limited settings (RLS) among adult men and women, comparing two randomized treatment arms. DESIGN: ACTG A5273 was a randomized clinical trial of second-line ART comparing lopinavir/ritonavir (LPV/r) + raltegravir (RAL) with LPV/r + nucleos(t)ide reverse transcriptase inhibitors (NRTIs) in participants failing a non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing regimen at 15 sites in 9 RLS...
January 13, 2018: AIDS
Sebastiano Leone, Milensu Shanyinde, Alessandro Cozzi Lepri, Fiona C Lampe, Pietro Caramello, Andrea Costantini, Andrea Giacometti, Andrea De Luca, Antonella Cingolani, Francesca Ceccherini Silberstein, Massimo Puoti, Andrea Gori, Antonella d'Arminio Monforte
To evaluate incidence rates of and predictors for any antiretroviral (ART) drug discontinuation by HCV infection status in a large Italian cohort of HIV infected patients. All patients enrolled in ICONA who started combination antiretroviral therapy (cART) containing abacavir or tenofovir or emtricitabine or lamivudine plus efavirenz or rilpivirine or atazanavir/r or darunavir/r (DRV/r) or lopinavir/r or dolutegravir or elvitegravir or raltegravir were included. Multivariate Poisson regression models were used to determine factors independently associated with single ART drug discontinuation...
January 9, 2018: European Journal of Clinical Microbiology & Infectious Diseases
Moherndran Archary, Helen Mcllleron, Raziya Bobat, Phillip La Russa, Thobekile Sibaya, Lubbe Wiesner, Stefanie Hennig
BACKGROUND: In developing countries, malnutrition remains a common clinical syndrome at antiretroviral treatment (ART) initiation. Physiological changes due to malnutrition and during nutritional recovery could affect the pharmacokinetics of antiretroviral drugs. METHODS: HIV-infected children admitted with severe acute malnutrition were randomised to early or delayed initiation of lopinavir/ritonavir, abacavir and lamivudine using WHO weight-band dosage charts...
December 8, 2017: Pediatric Infectious Disease Journal
S Seang, L Schneider, T Nguyen, M P Lê, C Soulie, R Calin, F Caby, M-A Valantin, R Tubiana, L Assoumou, A-G Marcelin, G Peytavin, C Katlama
Background: Darunavir/ritonavir is a potent PI with a high genetic barrier and pharmacological robustness favourably investigated as monotherapy. Whether darunavir could be dose reduced in the context of monotherapy deserves investigation. Methods: Patients with HIV suppressed viraemia (plasma viral load <50 copies/mL for 12 months) under ART who had switched to darunavir/ritonavir monotherapy at 600/100 mg/day between 2013 and 2015 were included in this observational 48 week single-centre study...
February 1, 2018: Journal of Antimicrobial Chemotherapy
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