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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
#1
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/28520611/treatment-outcomes-of-third-line-antiretroviral-regimens-in-hiv-infected-thai-adolescents
#2
Wasana Prasitsuebsai, Jiratchaya Sophonphan, Kulkanya Chokephaibulkit, Jurai Wongsawat, Suparat Kanjanavanit, Pope Kosalaraksa, Chaiwat Ngampiyakul, Pakarat Sangkla, Rawiwan Hansudewechakul, Stephen J Kerr, Thanyawee Puthanakit, Jintanat Ananworanich
BACKGROUND: Efficacy and safety data of third-line antiretroviral (ARV) regimens in adolescents are limited. METHODOLOGY: This study enrolled HIV-infected Thais who were treated with third-line regimens consisting of darunavir/ritonavir (DRV/r), etravirine (ETR), tipranavir/ritonavir (TPV/r) or raltegravir (RAL). RESULTS: Fifty-four adolescents 2-17 years of age were enrolled from 8 sites and followed for 48 weeks. Reasons for switch were second-line failure (n=44) and toxicity to second-line regimens (n=10)...
May 16, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28481112/structure-based-optimization-of-thiophene-3-2-d-pyrimidine-derivatives-as-potent-hiv-1-non-nucleoside-reverse-transcriptase-inhibitors-with-improved-potency-against-resistance-associated-variants
#3
Dongwei Kang, Zengjun Fang, Boshi Huang, Xueyi Lu, Heng Zhang, Haoran Xu, Zhipeng Huo, Zhongxia Zhou, Zhao Yu, Qing Meng, Gaochan Wu, Xiao Ding, Ye Tian, Dirk Daelemans, Erik De Clercq, Christophe Pannecouque, Peng Zhan, Xinyong Liu
This work follows on from our initial discovery of a series of piperidine-substituted thiophene[3,2-d]pyrimidine HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTI) ( J. Med. Chem. 2016 , 59 , 7991 - 8007 ). In the present study, we designed, synthesized, and biologically tested several series of new derivatives in order to investigate previously unexplored chemical space. Some of the synthesized compounds displayed single-digit nanomolar anti-HIV potencies against wild-type (WT) virus and a panel of NNRTI-resistant mutant viruses in MT-4 cells...
May 25, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28403052/second-and-third-line-antiretroviral-therapy-for-children-and-adolescents-a-scoping-review
#4
REVIEW
Erica Lazarus, Simone Nicol, Lisa Frigati, Martina Penazzato, Mark F Cotton, Elizabeth Centeno-Tablante, Avy Violari, Liesl Nicol
BACKGROUND: The World Health Organization identified a need for evidence to inform revision of second- and third-line antiretroviral therapy (ART) options in children failing ART. We performed an in-depth scoping review of all available literature on second-line and subsequent ART regimens in children younger than 18 years. METHODS: We comprehensively searched, without language or date limitations, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, the World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials...
May 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28390117/different-cell-cycle-modulation-in-skov-3-ovarian-cancer-cell-line-by-anti-hiv-drugs
#5
Angelica Perna, Angela Lucariello, Carmine Sellitto, Iolanda Agliata, Maria Carleo, Vincenzo Sangiovanni, Vincenzo Esposito, Germano Guerra, Luigi Cobellis, Antonio De Luca
Anti-retroviral drugs used for the treatment of Human Immunodeficiency Virus (HIV) have proven to be effective even against cancer. Drawing from this background the aim of our research project was to evaluate the effects of anti-HIV drugs that belong to the Nucleoside and Nucleotide Reverse Transcriptase Inhibitors (NRTI, abacavir and tenofovir), Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI, efavirenz and etravirine) and Protease Inhibitors (PI, darunavir) on ovarian adenocarcinoma cell line (Skov-3)...
March 26, 2017: Oncology Research
https://www.readbyqxmd.com/read/28382208/etravirine-combined-with-antiretrovirals-other-than-darunavir-ritonavir-for-hiv-1-infected-treatment-experienced-adults-week-48-results-of-a-phase-iv-trial
#6
Eduardo Arathoon, Asad Bhorat, Rodica Silaghi, Herta Crauwels, Ludo Lavreys, Lotke Tambuyzer, Ben Van Baelen, Simon Vanveggel, Magda Opsomer
OBJECTIVE: VIOLIN (TMC125IFD3002; NCT01422330) evaluated the safety, tolerability, and pharmacokinetics of etravirine with antiretrovirals other than darunavir/ritonavir in HIV-1-infected patients. METHODS: In a 48-week, phase IV, single-arm, multicenter study, patients on prior antiretroviral therapy (⩾8 weeks) who needed to change regimen for virologic failure (viral load ⩾ 500 copies/mL) or simplification/adverse events (viral load < 50 copies/mL) received etravirine 200 mg bid with ⩾1 other active antiretroviral, excluding darunavir/ritonavir or only nucleoside/tide reverse transcriptase inhibitors...
2017: SAGE Open Medicine
https://www.readbyqxmd.com/read/28375119/physical-characterization-and-dissolution-performance-assessment-of-etravirine-solid-dispersions-prepared-by-spray-drying-process
#7
Pavan Kommavarapu, Arthanareeswari Maruthapillai, Kamaraj Palanisamy, Ravi Teja Koya
The aim of the current exertion was to prepare Solid Dispersion of Etravirine by Spray drying technique to enhance aqueous solubility and dissolution rate. Solid dispersions (SD) of Etravirine were prepared using Copovidone and Povidone-Copovidone in dichloromethane and physical properties were characterized by Scanning electron microscopy (SEM), X-Ray diffractometry (PXRD), Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC). SD's were evaluated for equilibrium solubility and in vitro drug release profile by dissolution testing...
November 2016: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28249574/reactivation-of-occult-hbv-infection-in-an-hiv-hcv-co-infected-patient-successfully-treated-with-sofosbuvir-ledipasvir-a-case-report-and-review-of-the-literature
#8
Gabriele Fabbri, Ilaria Mastrorosa, Alessandra Vergori, Valentina Mazzotta, Carmela Pinnetti, Susanna Grisetti, Mauro Zaccarelli, Adriana Ammassari, Andrea Antinori
BACKGROUND: Reactivation of occult or inactive Hepatitis B virus (HBV) infection during immunosuppressant treatments is well known and widely described in literature. The same observation has been made in Hepatitis C (HCV)-infected patients previously exposed to HBV and treated with interferon-free DAA treatments. Because of common transmission routes, persons may have been exposed to HCV, HBV and HIV, but few cases have been reported in this scenario to date. Frequency of HBV reactivation in HIV/HCV co-infected patients previously exposed to HBV and treated with DAA remains unclear...
March 1, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28207816/hiv-drug-therapy-duration-a-swedish-real-world-nationwide-cohort-study-on-infcarehiv-2009-2014
#9
Amanda Häggblom, Stefan Lindbäck, Magnus Gisslén, Leo Flamholc, Bo Hejdeman, Andreas Palmborg, Amy Leval, Eva Herweijer, Sverrir Valgardsson, Veronica Svedhem
BACKGROUND: As HIV infection needs a lifelong treatment, studying drug therapy duration and factors influencing treatment durability is crucial. The Swedish database InfCareHIV includes high quality data from more than 99% of all patients diagnosed with HIV infection in Sweden and provides a unique opportunity to examine outcomes in a nationwide real world cohort. METHODS: Adult patients who started a new therapy defined as a new 3rd agent (all antiretrovirals that are not N[t]RTIs) 2009-2014 with more than 100 observations in treatment-naive or treatment-experienced patients were included...
2017: PloS One
https://www.readbyqxmd.com/read/28177134/the-influence-of-combination-use-of-cyp450-inducers-on-the-pharmacokinetics-of-voriconazole-a-systematic-review
#10
REVIEW
T-Y Li, W Liu, K Chen, S-Y Liang, F Liu
WHAT IS KNOWN AND OBJECTIVES: Voriconazole is a triazole antifungal agent and is extensively metabolized via cytochrome P450 (CYP450); therefore, special precautions need to be taken when co-administered with a known CYP450 inducer, which may lead to treatment failure. The influence of some CYP450 inducers on the pharmacokinetics of voriconazole has been described in previous studies, but a systematic review was lacking. In this study, we carried out a systematic review to assess the influence of CYP450 inducers on the pharmacokinetic (PK) parameters of voriconazole...
April 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28129253/hiv-drug-resistance-mutations-in-non-b-subtypes-after-prolonged-virological-failure-on-nnrti-based-first-line-regimens-in-sub-saharan-africa
#11
Cissy Kityo, Jennifer Thompson, Immaculate Nankya, Anne Hoppe, Emmanuel Ndashimye, Colin Warambwa, Ivan Mambule, Joep J van Oosterhout, Kara Wools-Kaloustian, Silvia Bertagnolio, Philippa J Easterbrook, Peter Mugyenyi, A Sarah Walker, Nicholas I Paton
OBJECTIVE: To determine drug resistance mutation (DRM) patterns in a large cohort of patients failing nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line antiretroviral therapy regimens in programs without routine viral load (VL) monitoring and to examine intersubtype differences in DRMs. DESIGN: Sequences from 787 adults/adolescents who failed an NNRTI-based first-line regimen in 13 clinics in Uganda, Kenya, Zimbabwe, and Malawi were analyzed...
June 1, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28088884/dual-raltegravir-etravirine-combination-as-maintenance-regimen-in-virologically-suppressed-hiv-1-infected-patients
#12
Leonardo Calza, Eleonora Magistrelli, Vincenzo Colangeli, Roberto Manfredi, Marco Borderi, Nicolo' Rossi, Matteo Conti, Rita Mancini, Pierluigi Viale
BACKGROUND: Nucleoside reverse transcriptase inhibitor (NRTI)- and protease inhibitor (PI)-sparing antiretroviral regimens may be useful in selected human immune deficiency virus (HIV)-infected patients with resistance or intolerance to these drug classes. METHODS: This was an observational prospective study of patients on suppressive antiretroviral therapy containing two NRTIs plus one ritonavir-boosted PI who switched to a dual regimen containing raltegravir plus etravirine...
February 16, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28065890/impact-of-obesity-on-antiretroviral-pharmacokinetics-and-immuno-virological-response-in-hiv-infected-patients-a-case-control-study
#13
Vincent Madelain, Minh P Le, Karen Champenois, Charlotte Charpentier, Roland Landman, Veronique Joly, Patrick Yeni, Diane Descamps, Yazdan Yazdanpanah, Gilles Peytavin
Background: Obesity has high prevalence among HIV-infected patients. Increased adipose tissue mass affects the pharmacokinetics of numerous drugs, but few data are available for antiretroviral drugs. Objectives: In this study we aimed to explore the pharmacokinetics of antiretroviral drugs and the immuno-virological response in obese patients with HIV infection. Patients and methods: We examined data from 2009 to 2012 in our hospital's database for HIV-1-infected patients who received an antiretroviral drug (abacavir, emtricitabine, lamivudine, tenofovir, efavirenz, etravirine, nevirapine, atazanavir/ritonavir, darunavir/ritonavir, lopinavir/ritonavir or raltegravir)...
April 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28034359/hiv-1-drug-susceptibility-to-potential-second-and-third-line-antiretroviral-regimens-among-cameroonian-patients-evidence-from-a-cross-sectional-design
#14
Aubin J Nanfack, Desire Takou, Joseph Fokam, Romina Salpini, Maria M Santoro, Giulia Cappelli, Martin Baane, Suzie M Tetang, Josef Eberle, Lutz Gürtler, Francesca Ceccherini-Silberstein, Judith N Torimiro, Vittorio Colizzi, Carlo-Federico Perno, Alexis Ndjolo
BACKGROUND: Scale-up of antiretroviral therapy (ART) and the growing number of long-term treated patients may favor multi-HIV drug resistance (HIVDR) in resource-limited settings. Understanding the burden of HIVDR with ART-exposure may provide new insights for an effective long-term management of infected patients. METHODS: Sixty-six HIV-infected individuals (18 ART-naïve, 24 failing first-line, 24 failing second-line ART) living in Yaoundé-Cameroon were evaluated by sequencing protease-reverse transcriptase (PR-RT, n=62), envelope-V3 loop (V3, n=58) and integrase (IN, n=30) regions...
December 29, 2016: Current HIV Research
https://www.readbyqxmd.com/read/28008980/antiretroviral-treatment-with-efavirenz-disrupts-the-blood-brain-barrier-integrity-and-increases-stroke-severity
#15
Luc Bertrand, Levi Dygert, Michal Toborek
The introduction of antiretroviral drugs (ARVd) changed the prognosis of HIV infection from a deadly disease to a chronic disease. However, even with undetectable viral loads, patients still develop a wide range of pathologies, including cerebrovascular complications and stroke. It is hypothesized that toxic side effects of ARVd may contribute to these effects. To address this notion, we evaluated the impact of several non-nucleoside reverse transcriptase inhibitors (NNRTI; Efavirenz, Etravirine, Rilpivirine and Nevirapine) on the integrity of the blood-brain barrier, and their impact on severity of stroke...
December 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27999009/use-of-a-physiologically-based-pharmacokinetic-model-to-simulate-drug-drug-interactions-between-antineoplastic-and-antiretroviral-drugs
#16
José Moltó, Rajith Rajoli, David Back, Marta Valle, Cristina Miranda, Andrew Owen, Bonaventura Clotet, Marco Siccardi
Background: Co-administration of antineoplastics with ART is challenging due to potential drug-drug interactions (DDIs). However, trials specifically assessing such DDIs are lacking. Our objective was to simulate DDIs between the antineoplastics erlotinib and gefitinib with key antiretroviral drugs and to predict dose adjustments using a physiologically based pharmacokinetic (PBPK) model. Methods: In vitro data describing chemical properties and pharmacokinetic processes of each drug and their effect on cytochrome P450 isoforms were obtained from the literature...
March 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27997522/second-and-third-line-antiretroviral-therapy-for-children-and-adolescents-a-scoping-review
#17
Erica Lazarus, Simone Nicol, Lisa Frigati, Martina Penazzato, Mark F Cotton, Elizabeth Centeno-Tablante, Avy Violari, Liesl Nicol
BACKGROUND: The World Health Organization (WHO) identified a need for evidence to inform revision of second and third-line antiretroviral therapy (ART) options in children failing ART. We performed an in-depth scoping review of all available literature on second and subsequent line ART regimens in children younger than 18 years. METHODS: We comprehensively searched, without language or date limitations, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the WHO International Clinical Trials Registry Platform and ClinicalTrials...
December 15, 2016: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/27923946/prevalence-of-antiretroviral-drug-resistance-in-patients-who-are-not-responding-to-protease-inhibitor-based-treatment-results-from-the-first-national-survey-in-south-africa
#18
K Steegen, M Bronze, M A Papathanasopoulos, G van Zyl, D Goedhals, C Van Vuuren, W Macleod, I Sanne, W S Stevens, S C Carmona
Limited data exist on human immunodeficiency virus type 1 (HIV-1) resistance in patients who are not responding to protease inhibitor (PI)-based regimens in resource-limited settings. This study assessed resistance profiles in adults across South Africa who were not responding to PI-based regimens. pol sequencing was undertaken and submitted to the Stanford HIV Drug Resistance Database. At least 1 major PI mutation was detected in 16.4% of 350 participants. A total of 53.4% showed intermediate resistance to darunavir/ritonavir, whereas high-level resistance was not observed...
December 15, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27869478/etravirine-and-rilpivirine-drug-resistance-among-hiv-1-subtype-c-infected-children-failing-non-nucleoside-reverse-transcriptase-inhibitor-based-regimens-in-south-india
#19
Shanmugam Saravanan, Bagavathi Kausalya, Selvamurthi Gomathi, Sathasivam Sivamalar, Balakrishnan Pachamuthu, Poongulali Selvamuthu, Amrose Pradeep, Solomon Sunil, Sarvode N Mothi, Davey M Smith, Rami Kantor
We have analyzed reverse transcriptase (RT) region of HIV-1 pol gene from 97 HIV-infected children who were identified as failing first-line therapy that included first-generation non-nucleoside RT inhibitors (Nevirapine and Efavirenz) for at least 6 months. We found that 54% and 65% of the children had genotypically predicted resistance to second-generation non-nucleoside RT inhibitors drugs Etravirine (ETR) and Rilpivirine, respectively. These cross-resistance mutations may compromise future NNRTI-based regimens, especially in resource-limited settings...
June 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/27788239/interaction-between-darunavir-and-etravirine-is-partly-mediated-by-cyp3a5-polymorphism
#20
Leïla Belkhir, Laure Elens, Francis Zech, Nadtha Panin, Anne Vincent, Jean Cyr Yombi, Bernard Vandercam, Vincent Haufroid
OBJECTIVES: To assess the impact of the loss-of-function CYP3A5*3 allele (rs776746, 6986A>G SNP) on darunavir (DRV) plasma concentrations. METHODS: 135 HIV-1 infected patients treated with DRV-based therapy were included in the study and plasma samples were obtained immediately before drug intake in order to determine DRV trough concentrations using an ultra performance liquid chromatography method (UPLC) with diode-array detection (DAD). Noteworthy is the fact that in 16 (11...
2016: PloS One
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