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drug interaction HIV

Jacqueline L Olin, Olga Klibanov, Alexandre Chan, Linda M Spooner
OBJECTIVE: To describe data with selected malignancies in people living with HIV (PLWH) and HIV in individuals affected by both conditions and to summarize drug-drug interactions (DDIs) with clinical recommendations for point-of-care review of combination therapies. DATA SOURCES: Literature searches were performed (2005 to December 2018) in MEDLINE and EMBASE to identify studies of malignancies in PLWH in the modern era. STUDY SELECTION AND DATA EXTRACTION: Article bibliographies and drug interaction databases were reviewed...
February 15, 2019: Annals of Pharmacotherapy
Qingbo Liu, Yen-Ting Lai, Peng Zhang, Mark K Louder, Amarendra Pegu, Reda Rawi, Mangaiarkarasi Asokan, Xuejun Chen, Chen-Hsiang Shen, Gwo-Yu Chuang, Eun Sung Yang, Huiyi Miao, Yuge Wang, Anthony S Fauci, Peter D Kwong, John R Mascola, Paolo Lusso
Broadly neutralizing antibodies (bNAbs) represent a promising alternative to antiretroviral drugs for HIV-1 prevention and treatment. Selected antibodies to the CD4-binding site bolster envelope trimer binding via quaternary contacts. Here, we rationally engraft a new paratope, i.e., the extended heavy-chain framework region 3 (FR3) loop of VRC03, which mediates quaternary interaction, onto several potent bNAbs, enabling them to reach an adjacent gp120 protomer. The interactive quaternary surface is delineated by solving the crystal structure of two FR3 loop-chimeric antibodies...
February 13, 2019: Nature Communications
Robert van Domselaar, Duncan T Njenda, Rohit Rao, Anders Sönnerborg, Kamalendra Singh, Ujjwal Neogi
Human immunodeficiency virus type 1 subtype C (HIV-1C) has a natural deletion of a YPxL motif in its Gag-p6 late domain. This domain mediates the binding of Gag to host cell protein ALIX and subsequently facilitates viral budding. In a subset of HIV-1C infected individuals, the tetrapeptide insertion PYxE has been identified at the deleted YPxL motif site. Here, we report the consequences of PYxE insertion on the interaction with ALIX and the relevance regarding replication fitness and drug sensitivity. In our three HIV-1C cohorts, PYKE and PYQE were most prevalent among PYxE variants...
February 13, 2019: Journal of Virology
Soo Chan Carusone, Adrian Guta, Samantha Robinson, Darrell H Tan, Curtis Cooper, Bill O'Leary, Karen de Prinse, Grant Cobb, Ross Upshur, Carol Strike
BACKGROUND: Drug use is associated with increased morbidity and mortality but people who use drugs experience significant barriers to care. Data are needed about the care experiences of people who use drugs to inform interventions and quality improvement initiatives. The objective of this study is to describe and characterize the experience of acute care for people who use drugs. METHODS: We conducted a qualitative descriptive study. We recruited people with a history of active drug use at the time of an admission to an acute care hospital, who were living with HIV or hepatitis C, in Toronto and Ottawa, Canada...
February 13, 2019: Harm Reduction Journal
E Kelly Hester, Kevin Astle
OBJECTIVE: To review the efficacy and safety of dolutegravir (DTG) with rilpivirine (RPV) as a dual therapy regimen in the treatment of HIV-1 infection. DATA SOURCES: A literature search was performed using PubMed (1966 to January 2019) and Google Scholar (2014 to January 2019) with the search terms dolutegravir, rilpivirine, dual, and switch. Other resources included review articles and the manufacturer product label. STUDY SELECTION AND DATA EXTRACTION: All relevant English-language articles of studies assessing the efficacy and safety of switch therapy to DTG with RPV and review articles were included...
February 13, 2019: Annals of Pharmacotherapy
V Marie, M Gordon
Motivation: Commonly, protease inhibitor failure is characterized by the development of multiple protease resistance mutations (PRMs). While the impact of PRMs on therapy failure are understood, the introduction of Gag mutations with protease remains largely unclear. Results: Here, we utilized phylogenetic analyses and Bayesian network learning as tools to understand Gag-protease coevolution and elucidate the pathways leading to Lopinavir failure in HIV-1 subtype C infected patients...
February 12, 2019: Bioinformatics
Krishnan Balasubramanian
We review various mathematical and computational techniques for drug discovery exemplifying some recent works pertinent to group theory of nested structures of relevance to phylogeny, topological, computational and combinatorial methods for drug discovery for multiple viral infections. We have reviewed techniques from topology, combinatorics, graph theory and knot theory that facilitate topological and mathematical characterizations of protein-protein interactions, molecular-target interactions, proteomics, genomics and statistical data reduction procedures for a large set of starting chemicals in drug discovery...
February 8, 2019: Current Topics in Medicinal Chemistry
Kelly Bleasby, Kerry L Fillgrove, Robert Houle, Bing Lu, Jairam Palamanda, Deborah J Newton, Meihong Lin, Grace Hoyee Chan, Rosa I Sanchez
Doravirine is a novel non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus type 1 infection. In vitro studies were conducted to assess the potential for drug interactions with doravirine via major drug-metabolizing enzymes and transporters. Kinetic studies confirmed that cytochrome P450 (CYP) 3A plays a major role in the metabolism of doravirine, with ∼20-fold higher catalytic efficiency for CYP3A4 versus CYP3A5. Doravirine was not a substrate of breast cancer resistance protein (BCRP) and likely not a substrate of organic anion transporting polypeptide (OATP) 1B1 or 1B3...
February 11, 2019: Antimicrobial Agents and Chemotherapy
Hwa-Ping Feng, Luzelena Caro, Christine Fandozzi, Xiaoyan Chu, Zifang Guo, Jennifer Talaty, Deborah Panebianco, Katherine Dunnington, Lihong Du, William D Hanley, Iain P Fraser, Anna Mitselos, Jean-Francois Denef, Inge De Lepeleire, Jan N de Hoon, Corinne Vandermeulen, William L Marshall, Patricia Jumes, Xiaobi Huang, Monika Martinho, Robert Valesky, Joan R Butterton, Marian Iwamoto, Wendy W Yeh
The combination of the hepatitis C virus (HCV) NS5A inhibitor elbasvir and NS3/4A protease inhibitor grazoprevir is a potent, once-daily therapy indicated for the treatment of chronic HCV infection in individuals coinfected with human immunodeficiency virus-1 (HIV). We explored the pharmacokinetic interactions of elbasvir and grazoprevir with ritonavir and ritonavir-boosted HIV protease inhibitors in three phase 1 trials. Drug-drug interaction trials in healthy participants were conducted to evaluate the effect of ritonavir on the pharmacokinetics of grazoprevir ( N = 10) and the potential 2-way pharmacokinetic interaction of elbasvir ( N = 30) or grazoprevir ( N = 39) when coadministered with ritonavir-boosted atazanavir, lopinavir, or darunavir...
February 11, 2019: Antimicrobial Agents and Chemotherapy
Patcharapong Thangsunan, Sakunna Wongsaipun, Sila Kittiwachana, Nuttee Suree
Development of a highly accurate prediction model for protein-ligand inhibition has been a major challenge in drug discovery. Herein we describe a novel predictive model for the inhibition of HIV-1 integrase (IN)-LEDGF/p75 protein-protein interaction. The model was constructed using energy parameters approximated from molecular dynamics (MD) simulations and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) calculations. Chemometric analysis using partial least squares (PLS) regression revealed that solvent accessible surface area energy (ΔGSASA ) is the major determinant parameter contributing greatly to the prediction accuracy...
February 12, 2019: Journal of Biomolecular Structure & Dynamics
Timothy D Becker, Ari R Ho-Foster, Ohemaa B Poku, Shathani Marobela, Haitisha Mehta, Dai Thi Xuan Cao, Lyla S Yang, Lilo I Blank, Vincent Ikageng Dipatane, Letumile Rogers Moeng, Keneilwe Molebatsi, Marlene M Eisenberg, Frances K Barg, Michael B Blank, Philip Renison Opondo, Lawrence H Yang
Mental illness is a common comorbidity of HIV and complicates treatment. In Botswana, stigma impedes treatment of mental illness. We examined explanatory beliefs about mental illness, stigma, and interactions between HIV and mental illness among 42 adults, from HIV clinic and community settings, via thematic analysis of interviews. Respondents endorse witchcraft as a predominant causal belief, in addition to drug abuse and effects of HIV. Respondents describe mental illness as occurring "when the trees blossom," underscoring a conceptualization of it as seasonal, chronic, and often incurable and as worse than HIV...
February 9, 2019: Qualitative Health Research
Aaron S Devanathan, Daijha J C Anderson, Mackenzie L Cottrell, Erin M Burgunder, Ashley C Saunders, Angela D M Kashuba
Despite development of modern antiretrovirals with lower drug interaction potential than their predecessors, drug interaction challenges remain. Standard treatment regimens still require multiple antiretrovirals that may cause, or may be the target of, drug interactions. Additionally, people living with HIV are living longer, and often present with comorbid conditions that require concomitant long-term drug therapy. Also, treatment of infectious diseases in resource-limited settings can result in significant interactions...
February 10, 2019: Clinical Pharmacology and Therapeutics
Sonia Mediouni, Krishna Chinthalapudi, Mary K Ekka, Ippei Usui, Joseph A Jablonski, Mark A Clementz, Guillaume Mousseau, Jason Nowak, Venkat R Macherla, Jacob N Beverage, Eduardo Esquenazi, Phil Baran, Ian Mitchelle S de Vera, Douglas Kojetin, Erwann P Loret, Kendall Nettles, Souvik Maiti, Tina Izard, Susana T Valente
The intrinsically disordered HIV-1 Tat protein binds the viral RNA transactivation response structure (TAR), which recruits transcriptional cofactors, amplifying viral mRNA expression. Limited Tat transactivation correlates with HIV-1 latency. Unfortunately, Tat inhibitors are not clinically available. The small molecule didehydro-cortistatin A (dCA) inhibits Tat, locking HIV-1 in persistent latency, blocking viral rebound. We generated chemical derivatives of dCA that rationalized molecular docking of dCA to an active and specific Tat conformer...
February 5, 2019: MBio
Vinod Sharma, Aditi Sharma
With increasing trend of polypharmacy, there are higher chances of drug-drug interactions leading to adverse effects, especially in psychiatric patients with co-morbid chronic medical problems. This case demonstrates a schizoaffective 30-year-old male on highly active antiretroviral therapy (HAART) who reported an incident of priapism potentially caused by an interaction between previously prescribed atypical antipsychotic, trazodone, norepinephrine dopamine reuptake inhibitor (NDRI), HAART, and newly added selective serotonin reuptake inhibitor (SSRI)...
2019: Case Reports in Psychiatry
Fedora Grande, Maria Antonietta Occhiuzzi, Bruno Rizzuti, Giuseppina Ioele, Michele De Luca, Paola Tucci, Valentina Svicher, Stefano Aquaro, Antonio Garofalo
HIV entry in the host cell requires the interaction with the CD4 membrane receptor, and depends on the activation of one or both co-receptors CCR5 and CXCR4. Former selective co-receptor antagonists, acting at early stages of infection, are able to impair the receptor functions, preventing the viral spread toward AIDS. Due to the capability of HIV to develop resistance by switching from CCR5 to CXCR4, dual co-receptor antagonists could represent the next generation of AIDS prophylaxis drugs. We herein present a survey on relevant results published in the last few years on compounds acting simultaneously on both co-receptors, potentially useful as preventing agents or in combination with classical anti-retroviral drugs based therapy...
February 2, 2019: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Pruthu Thekkur, Ajay Nv Kumar, Palanivel Chinnakali, Sriram Selvaraju, Ramachandra Bairy, Akash Ranjan Singh, Abhay Nirgude, Kalaiselvi Selvaraj, Vinayagamoorthy Venugopal, Suresh Shastri
BACKGROUND: In India, a new care package consisting of (i) daily regimen with fixed-dose combination drugs, collected once-a-month and self-administered by the patient, (ii) 'one stop service' at antiretroviral treatment (ART) centre for both HIV and tuberculosis (TB) treatment and (iii) technology-enabled adherence support (99DOTS, which required patients to give a missed phone call after consuming drugs) was piloted for treatment of TB among HIV-infected TB patients. Conventional care included intermittent regimen (drugs consumed thrice-weekly) delivered under direct observation of treatment supporter and the patients needing to visit TB and HIV care facilities, separately for treatment...
2019: Global Health Action
Jing Kou, Yi-Qun Kuang
Chemokines are a class of chemotactic small molecule peptides whose receptors CCR5 and CXCR4 play important role in the entry of human immunodeficiency virus (HIV-1) into immune cells. Chemokines belong to G protein-coupled receptor superfamily containing seven hydrophobic transmembrane helices, causing physiological effects such as chemotaxis, immune regulation, antiviral immunity, regulation of hematopoiesis and angiogenesis, as well as cell growth and metabolism, through certain signaling pathways. Earlier studies have shown that HIV infects the human immune cells by binding to the CD4 receptor...
2019: Progress in Molecular Biology and Translational Science
Eric W Djimeu, Anna C Heard
Co-diagnosis of HIV and tuberculosis presents a treatment dilemma. Starting both treatments at the same time can cause a flood of immune response called immune reconstitution inflammatory syndrome (IRIS) which can be lethal. But, how long to delay HIV treatment is less understood. In 2011, based on the conclusions of three separate studies, WHO recommended starting HIV treatment earlier for those with later HIV disease progression. This paper conducts a replication study of one of the three studies, by Havlir and colleagues...
2019: PloS One
David D Waters, Priscilla Y Hsue
Lipid abnormalities are prevalent among persons living with HIV infection and contribute to increasing the risk of cardiovascular events. Antiretroviral therapy (ART) is associated with lipid abnormalities, most commonly hypertriglyceridemia, but also increases in low-density lipoprotein cholesterol and total cholesterol. Different classes of ART, and different drugs within classes, have differing effects on lipid levels, but in general newer drugs have more favourable effects compared with older ones. Low-level inflammation and chronic immune activation act on lipids through a variety of mechanisms to make them more atherogenic...
November 15, 2018: Canadian Journal of Cardiology
Dario Cattaneo, Amedeo Capetti, Giuliano Rizzardini
The GEMINI trials have recently shown that a 2-drug regimen of dolutegravir plus lamivudine was non-inferior to a three-drug regimen in HIV-infected naïve patients. Accordingly, it is important that physicians be aware and confident about the drug-drug interactions (DDIs) involving dolutegravir, lamivudine and other medications. Areas covered: Here, we firstly update the available information on the pharmacokinetic features of dolutegravir and lamivudine; subsequently, the articles mainly deals with the predictable drug-drug interactions (DDIs) for both antiretroviral drugs, attempting to underline their clinical implications...
January 31, 2019: Expert Opinion on Drug Metabolism & Toxicology
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