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https://www.readbyqxmd.com/read/28621159/dual-antiretroviral-therapy-for-hiv-infection
#1
Vicente Soriano
For two decades' triple combinations of antiretrovirals have been the standard treatment for HIV infection. The challenges of such lifelong therapy include long-term side effects, high costs and reduced drug adherence. The recent advent of more potent and safer antiretrovirals has renewed the interest for simpler HIV regimens. Areas covered: We discuss the pros and cons of dual antiretroviral therapies in both drug-naïve and in treatment-experienced patients with viral suppression (switch strategy). Expert Opinion: Some dual antiretroviral regimens are safe and efficacious, particularly as maintenance therapy...
June 16, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28598790/croi-2017-advances-in-antiretroviral-therapy
#2
Joyce Jones, Barbara S Taylor, Hong-Van Tieu, Timothy J Wilkin
The 2017 Conference on Retroviruses and Opportunistic Infections (CROI) featured exciting preclinical data on investigational antiretroviral agents with good in vitro efficacy and long half-lives. Investigational medications, including bictegravir, demonstrated excellent efficacy and tolerability, as did dual-agent therapy with dolutegravir paired with rilpivirine or with lamivudine. Dolutegravir monotherapy proved inadvisable due to virologic failure and resistance. The gap between high- and low-income settings along the HIV care continuum is narrowing, with Zimbabwe, Malawi, and Zambia approaching the 90-90-90 targets established by the joint United Nations Programme on HIV/AIDS (UNAIDS), whereas communities in the Southern United States are falling behind...
May 2017: Topics in Antiviral Medicine
https://www.readbyqxmd.com/read/28595298/lowered-rilpivirine-exposure-during-third-trimester-of-pregnancy-in-hiv-1-positive-women
#3
Stein Schalkwijk, Angela Colbers, Deborah Konopnicki, Andrea Gingelmaier, John Lambert, Marchina van der Ende, José Moltó, David Burger
Background: The use of antiretroviral therapy during pregnancy is important for control of maternal HIV disease and the prevention of perinatal HIV transmission. Physiological changes during pregnancy can reduce antiretroviral exposure. We studied the pharmacokinetics of rilpivirine 25 mg once daily (QD) in HIV-1-positive women during late pregnancy. Methods: We conducted a non-randomized, open-label, multi-centre, phase-IV study. HIV-positive pregnant women receiving rilpivirine 25 mg QD were included...
June 8, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
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
#4
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/28579016/executive-summary-of-the-gesida-national-aids-plan-consensus-document-on-antiretroviral-therapy-in-adults-infected-by-the-human-immunodeficiency-virus-updated-january-2017
#5
(no author information available yet)
Antiretroviral therapy (ART) is recommended for all patients infected by HIV-1. The objective of ART is to achieve an undetectable plasma viral load (PVL). Initial ART should be based on a combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors (tenofovir in either of its two formulations plus emtricitabine or abacavir plus lamivudine) and another drug from a different family. Four of the recommended regimens, all of which have an integrase inhibitor as the third drug (dolutegravir, elvitegravir boosted with cobicistat or raltegravir), are considered preferential, whereas a further 3 regimens (based on elvitegravir/cobicistat, rilpivirine, or darunavir boosted with cobicistat or ritonavir) are considered alternatives...
May 31, 2017: Enfermedades Infecciosas y Microbiología Clínica
https://www.readbyqxmd.com/read/28569550/ultra-deep-sequencing-analysis-on-hiv-drug-resistant-associated-mutations-among-hiv-infected-individuals-first-report-from-the-philippines
#6
Ivo Novita SahBandar, Genesis Samonte, Elizabeth Telan, Nalyn Siripong, Mahdi Belcaid, David Schanzenbach, Susan Leano, Haorile Chagan-Yasutan, Toshio Hattori, Cecilia Shikuma, Lishomwa C Ndhlovu
OBJECTIVE: A sharp increase in the number of people living with HIV (PLHIV) has been documented in the Philippines. In response, the government has instituted antiretroviral therapy (ART) nationwide through HIV treatment hubs. However, no data presently exists on the status of ART drug-resistant-associated mutations (DRMs). In this study, we aim to analyze DRM profiles in the Philippines and provide comprehensive data on DRMs to guide treatment decisions and prevent viral failures. DESIGN AND METHODS: We conducted a cross-sectional study in 119 volunteers tested positive for HIV from over 8,000 participants screened for HIV across the nation through 2013 Integrated HIV Behavioral and Serologic Surveillance (IHBSS) program...
June 1, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28540638/in-silico-dose-prediction-for-long-acting-rilpivirine-and-cabotegravir-administration-to-children-and-adolescents
#7
Rajith K R Rajoli, David J Back, Steve Rannard, Caren Freel Meyers, Charles Flexner, Andrew Owen, Marco Siccardi
BACKGROUND AND OBJECTIVES: Long-acting injectable antiretrovirals represent a pharmacological alternative to oral formulations and an innovative clinical option to address adherence and reduce drug costs. Clinical studies in children and adolescents are characterised by ethical and logistic barriers complicating the identification of dose optimisation. Physiologically-based pharmacokinetic modelling represents a valuable tool to inform dose finding prior to clinical trials. The objective of this study was to simulate potential dosing strategies for existing long-acting injectable depot formulations of cabotegravir and rilpivirine in children and adolescents (aged 3-18 years) using physiologically-based pharmacokinetic modelling...
May 24, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28507107/in-vitro-cross-resistance-profiles-of-rilpivirine-dapivirine-and-miv-150-nnrti-microbicides-in-clinical-development-for-the-prevention-of-hiv-1-infection
#8
Nicholas S Giacobbi, Nicolas Sluis-Cremer
Rilpivirine, dapivirine (DPV) and MIV-150 are in development as microbicides. It is not known whether they will block infection of circulating NNRTI-resistant HIV-1 variants. Here, we demonstrate that the activity of DPV and MIV-150 are compromised by many resistant viruses containing single or double substitutions. High DPV genital tract concentrations from DPV-ring use may block replication of resistant viruses. However, MIV-150 genital tract concentrations may be insufficient to inhibit many resistant viruses, including those harboring K103N or Y181C...
May 15, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28484509/factors-associated-with-pre-treatment-hiv-rna-application-for-the-use-of-abacavir-and-rilpivirine-as-the-first-line-regimen-for-hiv-infected-patients-in-resource-limited-settings
#9
Sasisopin Kiertiburanakul, David Boettiger, Oon Tek Ng, Nguyen Van Kinh, Tuti Parwati Merati, Anchalee Avihingsanon, Wing-Wai Wong, Man Po Lee, Romanee Chaiwarith, Adeeba Kamarulzaman, Pacharee Kantipong, Fujie Zhang, Jun Yong Choi, Nagalingeswaran Kumarasamy, Rossana Ditangco, Do Duy Cuong, Shinichi Oka, Benedict Lim Heng Sim, Winai Ratanasuwan, Penh Sun Ly, Evy Yunihastuti, Sanjay Pujari, Jeremy L Ross, Matthew Law, Somnuek Sungkanuparph
BACKGROUND: Abacavir and rilpivirine are alternative antiretroviral drugs for treatment-naïve HIV-infected patients. However, both drugs are only recommended for the patients who have pre-treatment HIV RNA <100,000 copies/mL. In resource-limited settings, pre-treatment HIV RNA is not routinely performed and not widely available. The aims of this study are to determine factors associated with pre-treatment HIV RNA <100,000 copies/mL and to construct a model to predict this outcome...
2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28476131/factors-associated-with-pre-treatment-hiv-rna-application-for-the-use-of-abacavir-and-rilpivirine-as-the-first-line-regimen-for-hiv-infected-patients-in-resource-limited-settings
#10
Sasisopin Kiertiburanakul, David Boettiger, Oon Tek Ng, Nguyen Van Kinh, Tuti Parwati Merati, Anchalee Avihingsanon, Wing-Wai Wong, Man Po Lee, Romanee Chaiwarith, Adeeba Kamarulzaman, Pacharee Kantipong, Fujie Zhang, Jun Yong Choi, Nagalingeswaran Kumarasamy, Rossana Ditangco, Do Duy Cuong, Shinichi Oka, Benedict Lim Heng Sim, Winai Ratanasuwan, Penh Sun Ly, Evy Yunihastuti, Sanjay Pujari, Jeremy L Ross, Matthew Law, Somnuek Sungkanuparph
BACKGROUND: Abacavir and rilpivirine are alternative antiretroviral drugs for treatment-naïve HIV-infected patients. However, both drugs are only recommended for the patients who have pre-treatment HIV RNA <100,000 copies/mL. In resource-limited settings, pre-treatment HIV RNA is not routinely performed and not widely available. The aims of this study are to determine factors associated with pre-treatment HIV RNA <100,000 copies/mL and to construct a model to predict this outcome...
May 5, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28472812/agreement-between-estimated-and-measured-renal-function-in-an-everyday-clinical-outpatient-setting-of-human-immunodeficiency-virus-infected-individuals
#11
Magnus Glindvad Ahlström, Andreas Kjær, Jan Gerstoft, Niels Obel
INTRODUCTION: Estimated renal function (eRF) has been widely implemented as a screening tool in handling human immunodeficiency virus (HIV)-infected individuals. Our primary objective was to investigate the agreement between measured renal function (mRF) and eRF in HIV-infected individuals in an everyday clinical setting. METHODS: A single-center study at the HIV-outpatient clinic at Copenhagen University Hospital, Rigshospitalet. Study period from January 1, 2004-June 1, 2015...
May 5, 2017: Nephron
https://www.readbyqxmd.com/read/28465101/drug-like-property-driven-optimization-of-4-substituted-1-5-diarylanilines-as-potent-hiv-1-non-nucleoside-reverse-transcriptase-inhibitors-against-rilpivirine-resistant-mutant-virus
#12
Lei Wei, Hui-Ling Wang, Li Huang, Chin-Ho Chen, Susan L Morris-Natschke, Kuo-Hsiung Lee, Lan Xie
On the basis of our prior structure-activity relationship (SAR) results, our current lead optimization of 1,5-diarylanilines (DAANs) focused on the 4-substituent (R(1)) on the central phenyl ring as a modifiable position related simultaneously to improved drug resistance profiles and drug-like properties. Newly synthesized p-cyanovinyl-DAANs (8a-8g) with different R(1) side chains plus prior active p-cyanoethyl-DAANs (4a-4c) were evaluated not only for anti-HIV potency against both wild-type HIV virus and rilpivirine-resistant (E138K, E138K+M184I) viral replication, but also for multiple drug-like properties, including aqueous solubility, lipophilicity, and metabolic stability in human liver microsomes and human plasma...
June 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28449051/viral-kinetics-in-semen-with-different-antiretroviral-families-in-treatment-na%C3%A3-ve-hiv-infected-patients-a-randomized-trial
#13
Alicia Gutierrez-Valencia, Omar J Benmarzouk-Hidalgo, Inmaculada Rivas-Jeremías, Nuria Espinosa, María Trujillo-Rodríguez, Tamara Fernandez-Magdaleno, Pompeyo Viciana, Luis F López-Cortés
Background: There are several regimens for starting antiretroviral treatment, but it remains unknown whether either of them is more advantageous regarding the time course and magnitude of HIV-RNA decay in semen. Objective: To evaluate the differential effect of different antiretroviral drug families on viral kinetics in seminal plasma of treatment-naïve HIV-infected patients. Methods: Phase II, randomized, open-label study in which participants were randomized 1:1:1 to receive tenofovir-DF plus emtricitabine, and either cobicistat-boosted elvitegravir (EVGcobi), rilpivirine (RPV), or ritonavir-boosted darunavir (DRVrtv)...
April 25, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28408657/negative-regulation-of-human-pregnane-x-receptor-by-microrna-18a-5p-evidence-for-suppression-of-microrna-18a-5p-expression-by-rifampin-and-rilpivirine
#14
Devinder Sharma, Abdullah A Turkistani, Wenjun Chang, Catherine Hu, Zhaoming Xu, Thomas K H Chang
Small noncoding microRNAs act as post-transcriptional regulators of gene expression involved in diverse biologic functions. Pregnane X receptor (PXR, NR1I2), a member of the superfamily of nuclear receptors, is a transcription factor governing the transport and biotransformation of various drugs and other chemicals. In the present study, we identified a specific microRNA (miR) involved in regulating the expression and functionality of human PXR (hPXR). According to bioinformatics analysis employing three commonly used algorithms (TargetScan, miRanda, and DIANA-microT-CDS), miR-18a-5p was predicted to be the top candidate microRNA regulator of hPXR...
July 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28402970/the-genotyping-resistance-profile-of-the-pol-gene-detected-in-blood-of-newly-diagnosed-hiv-positive-men-is-durably-archived-in-the-gut-whatever-the-time-of-initiation-of-cart
#15
Anne Emmanuelle Depincé, Elodie Dussert, Delphine Vergnon-Miszczycha, Abdelaye Keita, Sylvie Pillet, Elisabeth Botelho-Nevers, Anne Frésard, Amandine Gagneux-Brunon, Frédéric R Lucht, Xavier Roblin, Bruno Pozzetto, Stéphane Paul, Thomas Bourlet
OBJECTIVE: To evaluate the mutational patterns on the pol gene of the main HIV-1 strain archived in cell genome of 10 chronically infected men according to their clinical and therapeutic history. The genotyping resistance profiles were compared between the first blood plasma available at the time of HIV diagnosis and rectal biopsies and PBMC sampled 1-5 years after the initiation of combined antiretroviral therapy (cART). METHODS: HIV-1 RNA and cell-associated HIV-1 DNA were quantified by Abbott Real-Time HIV-1 and Generic HIV® DNA cell (Biocentric) assays...
April 13, 2017: Intervirology
https://www.readbyqxmd.com/read/28369542/variable-endothelial-cell-function-restoration-after-initiation-of-two-antiretroviral-regimens-in-hiv-infected-individuals
#16
P Echeverría, E Gómez-Mora, S Roura, A Bonjoch, J Puig, N Pérez-Alvarez, A Bayés-Genís, B Clotet, J Blanco, E Negredo
Background: The effect of ART on endothelial cell function is incompletely characterized. Methods: We performed a 24 week prospective, case-control and comparative pilot study of ART-naive HIV-infected patients who started a darunavir- or rilpivirine-based regimen, matched with non-HIV-infected volunteers, to compare changes at week 24 from baseline in levels of circulating endothelial cells (CECs), endothelial progenitor cells (EPCs) and circulating angiogenic cells, as well as changes in immune-activation markers...
March 22, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28368868/universal-antiretroviral-regimens-thinking-beyond-one-pill-once-a-day
#17
Jeffrey M Jacobson, Charles W Flexner
PURPOSE OF REVIEW: Poor adherence to oral antiretroviral treatment in a subpopulation of persons with HIV-1 infection interferes with the potential success of the drug regimens in treating the infection. Here, we review long-acting antiretroviral strategies currently in clinical development that could prove useful for the treatment of HIV-1 infection in individuals not succeeding with short-acting oral regimens. RECENT FINDINGS: Pharmaceutical nanotechnology has succeeded in creating two novel long-acting injectable antiretroviral compounds, carbotegravir and rilpivirine, which have completed early clinical trials demonstrating the safety, tolerability and prolonged antiretroviral activity...
July 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28368071/long-acting-agents-for-hiv-infection-biological-aspects-role-in-treatment-and-prevention-and-patient-s-perspective
#18
Stefano Rusconi, Simone Marcotullio, Antonella Cingolani
Current cART regimens are highly potent and well tolerated, but long-term toxicities, drug-drug interactions, lifetime costs and scarce option for multiclass failed patients could limit the efficacy of treatment itself. Long-acting formulations of antiretrovirals, which could potentially replace daily tablets, have been developed and are under investigation for prevention and treatment of HIV infection. Cabotegravir and rilpivirine represent the first drugs studied in this context. The aim of this review is to summarize the biological bases, the available information on completed and ongoing clinical trials and the potential development of long-acting regimens for the treatment and prevention of HIV infection...
April 3, 2017: New Microbiologica
https://www.readbyqxmd.com/read/28303548/long-acting-antiretrovirals-where-are-we-now
#19
REVIEW
Amesika N Nyaku, Sean G Kelly, Babafemi O Taiwo
PURPOSE OF REVIEW: Current HIV treatment options require daily use of combination antiretroviral drugs. Many persons living with HIV experience treatment fatigue and suboptimal adherence as a result. Long-acting antiretroviral drugs are being developed to expand options for HIV treatment. Here, we review the agents in development, and evaluate data from recent clinical trials. In addition, we anticipate challenges to successful widespread use of long-acting antiretrovirals. RECENT FINDINGS: Parenteral nanosuspensions of cabotegravir and rilpivirine, and dapivirine vaginal ring are the farthest in clinical development...
April 2017: Current HIV/AIDS Reports
https://www.readbyqxmd.com/read/28279181/a-mature-macrophage-is-a-principal-hiv-1-cellular-reservoir-in-humanized-mice-after-treatment-with-long-acting-antiretroviral-therapy
#20
Mariluz Araínga, Benson Edagwa, R Lee Mosley, Larisa Y Poluektova, Santhi Gorantla, Howard E Gendelman
BACKGROUND: Despite improved clinical outcomes seen following antiretroviral therapy (ART), resting CD4+ T cells continue to harbor latent human immunodeficiency virus type one (HIV-1). However, such cells are not likely the solitary viral reservoir and as such defining where and how others harbor virus is imperative for eradication measures. To such ends, we used HIV-1ADA-infected NOD.Cg-Prkdc (scid) Il2rg (tm1Wjl) /SzJ mice reconstituted with a human immune system to explore two long-acting ART regimens investigating their abilities to affect viral cell infection and latency...
March 9, 2017: Retrovirology
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