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Victoria Pilkington, Andrew Hill, Sophie Hughes, Nneka Nwokolo, Anton Pozniak
Background: Tenofovir/emtricitabine (TDF/FTC) used as pre-exposure prophylaxis (PrEP) has proven benefits in preventing HIV infection. Widespread use of TDF/FTC can only be justified if the preventative benefits outweigh potential risks of adverse events. A previous meta-analysis of TDF/FTC compared to alternative tenofovir alafenamide (TAF)/FTC for treatment found no significant difference in safety endpoints when used without ritonavir or cobicistat, but more evidence around the safety of TDF/FTC is needed to address concerns and inform widespread use...
October 1, 2018: Journal of Virus Eradication
Rahul Kumar, John Chen Hsiang, Jessica Tan, Prem Harichander Thurairajah
No abstract text is available yet for this article.
December 4, 2018: Clinical and Molecular Hepatology
J Gini, A Amara, Sujan D Penchala, David J Back, L Else, D Egan, J Chiong, Bala I Harri, Elkanah D Kabilis, Paul P Pama, M Stephen, Saye H Khoo
Herbal medication use amongst people living with human immunodeficiency virus (PLWH) is widespread and understudied. This study aimed to evaluate the prevalence of herbal medicine use amongst PLWH and possible contamination with antiretrovirals (ARVs). Countrywide collection of herbal samples sold by street vendors in Nigeria for the following indications: human immunodeficiency virus (HIV), acquired immune deficiency syndrome, fever and general weakness. Samples were screened using a validated liquid chromatography-mass spectrometry/mass spectrometry method for the presence of the following ARVs: efavirenz, nevirapine, lopinavir, darunavir, ritonavir, atazanavir, emtricitabine, tenofovir and lamivudine...
November 30, 2018: International Journal of STD & AIDS
Masanori Atsukawa, Akihito Tsubota, Hidenori Toyoda, Koichi Takaguchi, Makoto Nakamuta, Tsunamasa Watanabe, Toshifumi Tada, Akemi Tsutsui, Hiroki Ikeda, Hiroshi Abe, Keizo Kato, Haruki Uojima, Tadashi Ikegami, Toru Asano, Chisa Kondo, Mai Koeda, Tomomi Okubo, Taeang Arai, Ai Iwashita-Nakagawa, Norio Itokawa, Takashi Kumada, Katsuhiko Iwakiri
AIM: The aim of this study was to evaluate the efficacy and safety of community-based ombitasvir/paritaprevir/ritonavir plus ribavirin therapy for non-cirrhotic patients with hepatitis C virus (HCV) genotype 2a infection in a real-world setting. METHODS: Patients with HCV genotype 2a infection were enrolled in this study and received the therapy for 16 weeks at 11 specialized centers between October 2016 and July 2017. Among the 98 patients participating in the study, 4 patients were excluded because of the presence of cirrhosis and/or genotype 2b infection...
November 28, 2018: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Cathia Soulie, Maria Mercedes Santoro, Charlotte Charpentier, Alexandre Storto, Dimitrios Paraskevis, Domenico Di Carlo, William Gennari, Gaetana Sterrantino, Maurizio Zazzi, Carlo Federico Perno, Vincent Calvez, Diane Descamps, Francesca Ceccherini-Silberstein, Anne-Geneviève Marcelin
Background: Doravirine is a novel HIV-1 NNRTI recently shown to be non-inferior to both darunavir/ritonavir and efavirenz in combination therapy with two NRTIs in treatment-naive patients. Doravirine has an in vitro resistance profile that is distinct from other NNRTIs and retains activity against viruses containing the most frequently transmitted NNRTI mutations. Objectives: The aim of this study was to examine the prevalence of doravirine resistance-associated mutations in HIV-1-infected treatment-naive patients in Europe...
November 23, 2018: Journal of Antimicrobial Chemotherapy
Annette Bruchfeld, Karin Lindahl
Hepatitis C is a global health concern, with important implications in chronic kidney disease (CKD) due to its increased prevalence in this population. Patients with advanced CKD have until recently been excluded from the pivotal direct acting anti-viral (DAA) trials, which have demonstrated high virological cure numbers. Sofosbuvir-free DAAs dasabuvir, ombitasvir/paritaprevir/ritonavir with or without ribavirin, and elbasvir/grazoprevir are well-tolerated in patients with genotype 1 and 4 CHC with CKD 4 or 5 (including HD), with virologic cure rates of above 90%, in both single-arm and placebo-controlled studies...
November 26, 2018: Seminars in Dialysis
Taher Nassar, Ayala Rohald, Natalya Naraykin, Dinorah Barasch, Orit Amsalem, Ponnandy Prabhu, Moshe Kotler, Simon Benita
Lopinavir (LPV), an efficient drug for HIV infection treatment, was incorporated into biodegradable PLGA nanocapsules (NCs) embedded in microparticles (MCPs) using the spray-drying technique in an attempt to bypass the P-gp efflux and protect the drug from CYP3A pre-systemic metabolism without ritonavir (RTV). SEM observations confirmed the formation of NCs and their entrapment in the MCPs. LPV-loaded NCs and free LPV were released from the MCPs at pH of 7.4 as evidenced by in vitro release studies. Results obtained from rat studies showed a 2-fold higher bioavailability of LPV following oral administration of the optimal formulation than Kaletra®, the marketed drug, showing that when properly entrapped, LPV can be effectively protected from CYP degradation in the gut as well as from the liver following systemic absorption...
November 23, 2018: Journal of Drug Targeting
Antonio Di Biagio, Lucia Taramasso, Giovanni Cenderello
The recently approved interferon-free DAA (direct antiviral agents) regimens have shown not only to be effective in terms of sustained virological response (SVR) rates (> 90%) but also well tolerated in most hepatitis C virus (HCV) infected patients. Nevertheless HCV genotypes are different and only a small percentage of trials consider genotype 4 (GT4), which was associated with lower rates of SVR compared with other genotypes before the arrival of the DAA's. In this review, we discuss the efficacy of DAA therapy in GT4 HCV infection with specific reference to more recent studies, including those conducted in a 'field-practice' scenario...
November 22, 2018: Virology Journal
Priya Bhagwat, Ighovwerha Ofotokun, Grace A McComsey, Todd T Brown, Carlee Moser, Catherine A Sugar, Judith S Currier
Background: This study investigates the association of clinical and demographic predictors with abdominal fat gain, measured using waist circumference (WC) and self-reported abdominal size. Methods: We analyzed data from ACTG A5257, a clinical trial that randomized treatment-naïve HIV-infected participants to 1 of 3 antiretroviral regimens: raltegravir (RAL) or the protease inhibitors (PIs) atazanavir/ritonavir (ATV/r) or darunavir/ritonavir (DRV/r), each in combination with tenofovir disoproxil fumarate/emtricitabine...
November 2018: Open Forum Infectious Diseases
Nicola Squillace, Giorgio Bozzi, Elisa Colella, Andrea Gori, Alessandra Bandera
A fixed-dose combination consisting of darunavir (Drv), cobicistat (Cobi), emtricitabine (2',3'-dideoxy-5-fluoro-3'-thiacytidine [FTC]), and tenofovir alafenamide (Taf) has been recently approved by the European Medicines Agency for the treatment of HIV infection, and is the first ever protease-inhibitor-based single-tablet regimen. This article provides a detailed description of its pharmacokinetic, efficacy, and safety profile. The pharmacokinetics of single compounds were analyzed, with a special focus on contrasts between Drv/Cobi and Drv/ritonavir (Rtv)...
2018: Drug Design, Development and Therapy
Vanessa V S Castilho, Keyla C S Gonçalves, Karina M Rebello, Luiz P R Baptista, Leandro S Sangenito, Helena L C Santos, Marta H Branquinha, André L S Santos, Rubem F S Menna-Barreto, Ana C Guimarães, Claudia M d'Avila-Levy
OBJECTIVE: The low investment in research, diagnosis and treatment are factors that contribute to the continuity of Chagas' disease as a neglected tropical diseases (NTDs). In this context, the repositioning of drugs represents a useful strategy, in the search for new chemotherapeutic approaches for NTDs. HIV aspartic peptidase inhibitors (HIV IPs) are good candidates for drug repurposing. Here, we modeled the three dimensional structure of an aspartyl peptidase of Trypanosoma cruzi, the causative agent of Chagas' disease, aligned it to the HIV aspartyl peptidase and performed docking binding assays with the HIV PIs...
November 21, 2018: BMC Research Notes
Todd M Conner, Ronald C Reed, Tao Zhang
BACKGROUND AND OBJECTIVES: Lamotrigine (Lamictal® ) is a broad-spectrum antiepileptic drug available in both immediate-(IR) and extended-release (XR) formulations. Here, we present a new physiologically based pharmacokinetic (PBPK) model for IR and XR formulations of lamotrigine to predict disposition in adults and children, plus drug-drug interactions (DDIs). METHODS: Models for lamotrigine IR and XR formulations were constructed using a Simcyp® Simulator. Concentration-time profiles were simulated for lamotrigine IR single (SD ) and steady-state (SS) doses ranging from 25 to 200 mg in adults, as well as 2 mg/kg (SD ), and 7...
November 20, 2018: European Journal of Drug Metabolism and Pharmacokinetics
Mario R Sampson, Kelly Y Cao, Paula L Gish, Kyong Hyon, Poonam Mishra, William Tauber, Ping Zhao, Esther H Zhou, Islam R Younis
Although current quetiapine labeling recommends that its dosage should be lowered 6-fold when coadministered with strong cytochrome P450 (CYP)3A inhibitors, a reported case of coma in a patient receiving quetiapine with lopinavir and ritonavir prompted the reevaluation of labeling recommendations for the dosing of quetiapine when coadministered with human immunodeficiency virus (HIV) protease inhibitors. Literature and database (FDA Adverse Event Reporting System and United States Symphony Health Solutions' Integrated Dataverse Database) searches allowed us to identify cases of coma and related adverse events involving the coadministration of quetiapine and HIV protease inhibitors and to estimate the frequency of concomitant use...
November 19, 2018: Journal of Clinical Pharmacology
Fabrizio Fabrizi, Francesco Negro, Mark Bondin, Patrice Cacoub
Chronic HCV infection is a non-traditional (but modifiable) risk factor for chronic kidney disease and has been implicated in glomerular injury and nephrosclerotic disease. Three HCV direct-acting antiviral regimens are available for patients with severe kidney impairment: ombitasvir, paritaprevir with the pharmacokinetic enhancer ritonavir, and dasabuvir; glecaprevir plus pibrentasvir; and elbasvir plus grazoprevir. In patients with severe kidney impairment, sofosbuvir-free regimens are preferred because sofosbuvir accumulation has been associated with a progressive worsening of renal function...
2018: Antiviral Therapy
Jacinta A Holmes, Charles Carlton-Smith, Arthur Y Kim, Emily O Dumas, Joelle Brown, Jenna L Gustafson, Georg M Lauer, Sakuni T Silva, Maxwell Robidoux, Daniel Kvistad, Nadia Alatrakchi, Pierre Tonnerre, Daniel E Cohen, Hongtao Zhang, Nancy S Shulman, Raymond T Chung
The role of the endogenous interferon (IFN) system has been well characterized during IFN-based therapy for chronic hepatitis C virus (HCV) infection; less is known for direct-acting antivirals (DAAs). In this phase 3b open-label study, we assessed changes in IFN-stimulated genes (ISGs) in non-cirrhotic treatment-naïve or pegIFN/RBV-experienced HCV-GT1a-infected patients receiving paritaprevir/ritonavir/ombitasvir+dasabuvir+ribavirin (PrOD+R) for 12 weeks. ISG expression was quantified from PBMCs at baseline, treatment weeks (TW)2, TW4, TW8, end-of-treatment (EOT) and at post-treatment week 12...
November 19, 2018: Journal of Viral Hepatitis
Jose Vicente, Robbert Zusterzeel, Lars Johannesen, Roberto Ochoa-Jimenez, Jay W Mason, Carlos Sanabria, Sarah Kemp, Philip T Sager, Vikram Patel, Murali K Matta, Jiang Liu, Jeffry Florian, Christine Garnett, Norman Stockbridge, David G Strauss
Balanced multi-ion channel-blocking drugs have low torsade risk because they block inward currents. The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative proposes to use an in-silico cardiomyocyte model to determine the presence of balanced block, and absence of J-Tpeakc prolongation would be expected for balanced blockers. This study included 3 balanced blockers in a 10-subject per drug parallel-design; lopinavir/ritonavir and verapamil met the primary endpoint of ΔΔJ-Tpeakc upper bound <10 ms, while ranolazine did not (upper bounds of 8...
November 17, 2018: Clinical Pharmacology and Therapeutics
Ewa Janczewska, Dorota Zarębska-Michaluk, Hanna Berak, Anna Piekarska, Andrzej Gietka, Dorota Dybowska, Włodzimierz Mazur, Teresa Belica-Wdowik, Witold Dobracki, Magdalena Tudrujek-Zdunek, Zbigniew Deroń, Iwona Buczyńska, Marek Sitko, Agnieszka Czauż-Andrzejuk, Beata Lorenc, Jolanta Białkowska-Warzecha, Jolanta Citko, Łukasz Laurans, Jerzy Jaroszewicz, Łukasz Socha, Olga Tronina, Brygida Adamek, Andrzej Horban, Waldemar Halota, Barbara Baka-Ćwierz, Krzysztof Tomasiewicz, Krzysztof Simon, Aleksander Garlicki, Marta Wawrzynowicz-Syczewska, Robert Flisiak
BACKGROUND: According to the EASL and AASLD guidelines, the recommended treatment for patients who failed to achieve a sustained virologic response (SVR) on prior interferon-based triple therapy with protease inhibitors (PI), is a combination of sofosbuvir and NS5A inhibitors. Polish national recommendations also allow the use of paritaprevir/ritonavir/ombitasvir+dasasbuvir±ribavirin (PrODR) in this group of patients. The aim of the study was to evaluate the efficacy and safety of PrODR vs...
November 16, 2018: BMC Infectious Diseases
Michael Gschwantler, Thomas Bamberger, Ivo Graziadei, Andreas Maieron, Nives Katalinic, Rudolf Stauber
BACKGROUND: The direct-acting antiviral regimen of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) ± dasabuvir (DSV) ± ribavirin (RBV) is approved to treat patients with chronic hepatitis C (CHC) infection genotypes 1 or 4, including compensated cirrhosis. The aim of the prospective, multicenter, observational REAL study was to provide evidence of the effectiveness of this regimen in an Austrian real-world setting and to determine the impact on patient-reported outcomes (PROs)...
November 14, 2018: Wiener Klinische Wochenschrift
Jason Grebely, Massimo Puoti, Heiner Wedemeyer, Curtis Cooper, Mark S Sulkowski, Graham R Foster, Thomas Berg, Erica Villa, Federico Rodriguez-Perez, David L Wyles, Gretja Schnell, Negar N Alami, Zhenzhen Zhang, Emily Dumas, Gregory J Dore
Background: We evaluated the impact of opioid substitution therapy (OST) on the completion, adherence, efficacy, and safety of the 3-direct-acting antiviral regimen of ombitasvir, paritaprevir (identified by AbbVie and Enanta) co-dosed with ritonavir, and dasabuvir ± ribavirin among patients infected with hepatitis C virus (HCV) genotype (GT) 1, with or without compensated cirrhosis. Methods: Data were pooled from GT1-infected patients enrolled in 12 phase II/III/IIIb clinical trials and categorized by use of OST...
November 2018: Open Forum Infectious Diseases
Amanda Poissonnier, Jean-Philippe Guégan, Ha Thanh Nguyen, Daniel Best, Nicolas Levoin, Guennadi Kozlov, Kalle Gehring, Raphael Pineau, Florence Jouan, Lucie Morere, Sophie Martin, Mélissa Thomas, Estibaliz Lazaro, Isabelle Douchet, Thomas Ducret, Pierre van de Weghe, Patrick Blanco, Mickael Jean, Pierre Vacher, Patrick Legembre
CD95L is a transmembrane ligand (m-CD95L) that is cleaved by metalloproteases to release a soluble ligand (s-CD95L). Unlike m-CD95L, interaction between s-CD95L and CD95 fails to recruit caspase-8 and FADD to trigger apoptosis and instead induces a Ca2+ response via docking of PLCγ1 to the calcium-inducing domain (CID) within CD95. This signaling pathway induces accumulation of inflammatory Th17 cells in damaged organs of lupus patients, thereby aggravating disease pathology. A large-scale screen revealed that the HIV protease inhibitor ritonavir is a potent disruptor of the CD95-PLCγ1 interaction...
December 2018: Nature Chemical Biology
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