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https://www.readbyqxmd.com/read/28088905/update-on-recent-developments-in-small-molecular-hiv-1-rnase-h-inhibitors-2013-2016-opportunities-and-challenges
#1
Xueshun Wang, Ping Gao, Luis Menéndez-Arias, Xinyong Liu, Peng Zhan
Combinations of antiretroviral drugs are successfully used to treat HIV-infected patients. However, drug resistance is a major problem that makes discovery of new antiretroviral drugs an ongoing priority. The ribonuclease H (RNase H) activity of the HIV-1 reverse transcriptase catalyzes the selective hydrolysis of the RNA strand of RNA:DNA heteroduplex replication intermediates, and represents an attractive unexploited target for drug development. This review reports on recent progress in the characterization of HIV-1 RNase H inhibitors from 2013 to 2016, describing their chemical structures, structure-activity relationship and binding modes...
January 13, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28088884/dual-raltegravir-etravirine-combination-as-maintenance-regimen-in-virologically-suppressed-hiv-1-infected-patients
#2
Leonardo Calza, Eleonora Magistrelli, Vincenzo Colangeli, Roberto Manfredi, Marco Borderi, Nicolò 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 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. Patients were required not to have prior virological failure to raltegravir and to have efficacy of etravirine showed through the genotypic resistance assay in case of prior non-nucleoside reverse transcriptase inhibitor (NNRTI) virological failure...
January 15, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28086981/does-antiretroviral-treatment-change-hiv-1-codon-usage-patterns-in-its-genes-a-preliminary-bioinformatics-study
#3
Navaneethan Palanisamy, Nathan Osman, Frédéric Ohnona, Hong-Tao Xu, Bluma Brenner, Thibault Mesplède, Mark A Wainberg
BACKGROUND: Codon usage bias has been described for various organisms and is thought to contribute to the regulation of numerous biological processes including viral infections. HIV-1 codon usage has been previously shown to be different from that of other viruses and man. It is evident that the antiretroviral drugs used to restrict HIV-1 replication also select for resistance variants. We wanted to test whether codon frequencies in HIV-1 sequences from treatment-experienced patients differ from those of treatment-naive individuals due to drug pressure affecting codon usage bias...
January 7, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28081036/one-year-mortality-of-hiv-positive-patients-treated-for-rifampicin-and-isoniazid-susceptible-tuberculosis-in-eastern-europe-western-europe-and-latin-america
#4
(no author information available yet)
OBJECTIVES: The high mortality among HIV/tuberculosis (TB) coinfected patients in Eastern Europe is partly explained by the high prevalence of drug-resistant TB. It remains unclear whether outcomes of HIV/TB patients with rifampicin/isoniazid-susceptible TB in Eastern Europe differ from those in Western Europe or Latin America. METHODS: One-year mortality of HIV-positive patients with rifampicin/isoniazid-susceptible TB in Eastern Europe, Western Europe, and Latin America was analysed and compared in a prospective observational cohort study...
January 28, 2017: AIDS
https://www.readbyqxmd.com/read/28076335/infrequent-development-of-drug-resistance-in-hiv-1-infected-treatment-naive-subjects-after-96-weeks-of-treatment-with-elvitegravir-cobicistat-emtricitabine-tenofovir-alafenamide-or-elvitegravir-cobicistat-emtricitabine-tenofovir-disoproxil-fumarate
#5
Nicolas Margot, Stephanie Cox, Moupali Das, Scott McCallister, Michael D Miller, Christian Callebaut
BACKGROUND: Tenofovir alafenamide (TAF) is a novel prodrug of the nucleotide RT inhibitor (NtRTI) tenofovir (TFV) that loads lymphocytes with TFV-diphosphate more efficiently than tenofovir disoproxil fumarate (TDF). The single-tablet regimen (STR) composed of elvitegravir/cobicistat/emtricitabine/TAF (E/C/F/TAF) has demonstrated non-inferiority to the STR of E/C/F/TDF in clinical studies, with high proportions of subjects achieving HIV-1 RNA <50 copies/mL at week 48, and maintained through week 96...
January 11, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28068521/hiv-and-its-relationship-to-insulin-resistance-and-lipid-abnormalities
#6
REVIEW
Lemuel R Non, Gerome V Escota, William G Powderly
Antiretroviral therapy has revolutionized the care of people with human immunodeficiency virus (HIV) by reducing morbidity and mortality from acquired immunodeficiency syndrome-related conditions. Despite longer life expectancy, however, HIV-infected individuals continue to have a higher risk of death compared with the general population. This has been attributed to the increasing incidence of noncommunicable diseases, in particular, atherosclerotic cardiovascular diseases. This is driven, in part, by the emergence of metabolic disorders, particularly dyslipidemia, insulin resistance, and lipodystrophy, in those on antiretroviral therapy...
December 23, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28067719/insulin-resistance-and-markers-of-inflammation-in-hiv-infected-ugandan-children-in-the-chapas-3-trial
#7
Sahera Dirajlal-Fargo, Victor Musiime, Adrian Cook, Grace Mirembe, Julia Kenny, Ying Jiang, Sara Debanne, Nigel Klein, Grace A Mccomsey
BACKGROUND: Few studies have investigated metabolic complications in HIV-infected African children and their relation with inflammation. METHODS: We compared baseline and changes in insulin resistance (HOMA-IR) and in markers of inflammation over 48 weeks, in a subset of antiretroviral therapy (ART) naïve Ugandan children from the CHAPAS-3 trial randomized to zidovudine (AZT), stavudine (D4T) or abacavir (ABC) based regimens. Non-parametric methods were used to explore between and within group differences and multivariable analyses to assess associations of HOMA-IR...
January 6, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28059958/future-technologies-for-monitoring-hiv-drug-resistance-and-cure
#8
Urvi M Parikh, Kevin McCormick, Gert van Zyl, John W Mellors
PURPOSE OF REVIEW: Sensitive, scalable and affordable assays are critically needed for monitoring the success of interventions for preventing, treating and attempting to cure HIV infection. This review evaluates current and emerging technologies that are applicable for both surveillance of HIV drug resistance (HIVDR) and characterization of HIV reservoirs that persist despite antiretroviral therapy and are obstacles to curing HIV infection. RECENT FINDINGS: Next-generation sequencing (NGS) has the potential to be adapted into high-throughput, cost-efficient approaches for HIVDR surveillance and monitoring during continued scale-up of antiretroviral therapy and rollout of preexposure prophylaxis...
January 5, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28059955/diagnosis-of-opportunistic-infections-hiv-co-infections-tuberculosis
#9
Lesley Scott, Pedro da Silva, Catharina C Boehme, Wendy Stevens, Chris Gilpin
PURPOSE OF REVIEW: Tuberculosis (TB) incidence has declined ∼1.5% annually since 2000, but continued to affect 10.4 million individuals in 2015, with 1/3 remaining undiagnosed or underreported. The diagnosis of TB among those co-infected with HIV is challenging as TB remains the leading cause of death in such individuals. Accurate and rapid diagnosis of active TB will avert mortality in both adults and children, reduce transmission, and assist in timeous decisions for antiretroviral therapy initiation...
January 5, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28053103/cytokines-elevated-in-hiv-elite-controllers-reduce-hiv-replication-in-vitro-and-modulate-hiv-restriction-factor-expression
#10
Evan S Jacobs, Sheila M Keating, Mohamed Abdel-Mohsen, Stuart L Gibb, John W Heitman, Heather C Inglis, Jeffrey N Martin, Jinbing Zhang, Zhanna Kaidarova, Xutao Deng, Shiquan Wu, Kathryn Anastos, Howard Crystal, Maria C Villacres, Mary Young, Ruth M Greenblatt, Alan L Landay, Stephen J Gange, Steven G Deeks, Elizabeth T Golub, Satish K Pillai, Philip J Norris
: A subset of HIV infected individuals termed elite controllers (ECs) maintain CD4+ T cell counts and control viral replication in the absence of antiretroviral therapy (ART). Systemic cytokine responses may differentiate ECs from subjects with uncontrolled viral replication or those who require ART to suppress viral replication. We measured 87 cytokines in four groups of women: 73 EC, 42 with pharmacologically suppressed viremia (ART), 42 with uncontrolled viral replication (noncontrollers, NC), and 48 HIV uninfected (NEG) subjects...
January 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28051809/pregnancy-related-changes-of-antiretroviral-pharmacokinetics-an-argument-for-tdm
#11
Francesco R Simonetti, Dario Cattaneo, Nadia Zanchetta, Vania Giacomet, Valeria Micheli, Nadia Ciminera, Cristina Gervasoni
Here we describe a case of an HIV-infected young woman with extensive drug-resistant virus, who was successfully switched from a raltegravir-based regimen to a dolutegravir-based intensified antiretroviral regimen a few days before scheduled caesarean section because of the still detectable viral load. The trough concentrations of all antiretroviral drugs before and after delivery are also described.Our case underlines both the difficult management of young women, HIV-infected at young age with very limited treatment options and the great variability in the pregnancy-related physiologic changes affecting the pharmacokinetics of antiretrovirals...
January 4, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28043170/impact-of-disease-drug-and-patient-adherence-on-the-effectiveness-of-antiviral-therapy-in-pediatric-hiv
#12
Chiara Piana, Meindert Danhof, Oscar Della Pasqua
Maintaining effective antiretroviral treatment for life is a major problem, in both resource-limited and resource-rich countries. Despite the progress observed in paediatric antiretroviral therapy, approximately 12% of children still experience treatment failure due to drug resistance, inadequate dosing and poor adherence. We explore the current status of antiretroviral therapy in children with focus on the interaction between disease, drug pharmacokinetics and patient behavior, all of which are strongly interconnected and determine treatment outcome...
January 3, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28038962/confirming-model-predicted-pharmacokinetic-interactions-between-bedaquiline-and-lopinavir-ritonavir-or-nevirapine-in-patients-with-hiv-and-drug-resistant-tuberculosis
#13
Margreke J E Brill, Elin M Svensson, Mishal Pandie, Gary Maartens, Mats O Karlsson
Bedaquiline and its metabolite M2 are metabolised by CYP3A4. The antiretrovirals ritonavir-boosted lopinavir (LPV/r) and nevirapine inhibit and induce CYP3A4, respectively. Here we aimed to quantify nevirapine and LPV/r drug-drug interaction effects on bedaquiline and M2 in patients co-infected with HIV and multidrug-resistant tuberculosis (MDR-TB) using population pharmacokinetic (PK) analysis and compare these with model-based predictions from single-dose studies in subjects without TB. An observational PK study was performed in three groups of MDR-TB patients during bedaquiline maintenance dosing: HIV-seronegative patients (n = 17); and HIV-infected patients using antiretroviral therapy including nevirapine (n = 17) or LPV/r (n = 14)...
December 14, 2016: International Journal of Antimicrobial Agents
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/28018931/virologic-failure-and-human-immunodeficiency-virus-drug-resistance-in-rural-cameroon-with-regard-to-the-unaids-90-90-90-treatment-targets
#15
Charlotte Boullé, Emilande Guichet, Charles Kouanfack, Avelin Aghokeng, Benjamin Onambany, Catherine Massama Ikaka, Emile Ngock, Landry Tsoumsta, Philippe Msellati, Eitel Mpoudi-Ngolé, Martine Peeters, Eric Delaporte, Christian Laurent
BACKGROUND: In rural Africa, data on virologic effectiveness of antiretroviral treatment (ART) are not sufficient to assess the gap with the UNAIDS 90-90-90 treatment targets. We investigated the prevalences of unsuppressed viral load and antiretroviral drug resistance and the profile of genotypic resistance mutations among patients routinely treated in rural Cameroon. METHODS: A cross-sectional study was performed in 2013-2014 among patients ≥15 years and on first-line ART for ≥6 months in a district hospital...
October 2016: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28018925/parasite-clearance-and-artemether-pharmacokinetics-parameters-over-the-course-of-artemether-lumefantrine-treatment-for-malaria-in-human-immunodeficiency-virus-hiv-infected-and-hiv-uninfected-ugandan-children
#16
Richard Kajubi, Liusheng Huang, Moses Were, Sylvia Kiconco, Fangyong Li, Florence Marzan, David Gingrich, Myaing M Nyunt, Joshua Ssebuliba, Norah Mwebaza, Francesca T Aweeka, Sunil Parikh
BACKGROUND: Artemisinins are primarily responsible for initial parasite clearance. Antimalarial pharmacokinetics (PK), human immunodeficiency virus (HIV) infection, and antiretroviral therapy have been shown to impact treatment outcomes, although their impact on early parasite clearance in children has not been well characterized. METHODS: Parasite clearance parameters were generated from twice-daily blood smears in HIV-infected and HIV-uninfected Ugandan children treated with artemether-lumefantrine (AL)...
October 2016: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28017912/differences-in-the-integrase-and-reverse-transcriptase-transmitted-resistance-patterns-in-northern-poland
#17
Miłosz Parczewski, Magdalena Leszczyszyn-Pynka, Anna Urbańska
INTRODUCTION: With the widespread introduction of the integrase (In) inhibitors into clinical practice, transmission of drug resistance to this class of antiretroviral medications may expand. The aim of this study was to analyze the recent patterns of In resistance in treatment naive individuals in Northern Poland and its association with transmitted protease (PR) and reverse transcriptase (RT) mutations. METHODS: Study included 172 PR, RT and InI sequences from antiretroviral treatment naive HIV-1 infected patients linked to care in Northern Poland from 2010 to 2015...
December 22, 2016: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28017554/trends-and-predictors-of-hiv-1-acquired-drug-resistance-in-minas-gerais-brazil-2002-2012
#18
Helena Duani, Agdemir Waleria Aleixo, Unaí Tupinambás
Several studies show that the prevalence of multidrug-resistant HIV-1 virus is declining over time. A retrospective cohort study was carried out to evaluate the trends of drug resistance in antiretroviral treatment-exposed (ART) individuals in a state of a middle-income country, Minas Gerais, southeast region of Brazil. We analyzed 2115 HIV-1 sequences from 2002 up to 2012, from 52 cities of Minas Gerais. The groups were analyzed according to the definitions: "IAS - 3 class mutations", if ≥1 drug resistance mutation from IAS 2015 list (DRM) was present in each class; "No fully susceptible drugs" as the absence of any fully susceptible drug in Stanford algorithm; and "GSS≥2", when a maximum calculated GSS (genotypic susceptibility score) was ≥2 or ≥3, counting only drugs available in Brazil and USA at given calendar years...
December 22, 2016: Brazilian Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28010730/from-antiretroviral-therapy-access-to-provision-of-third-line-regimens-evidence-of-hiv-drug-resistance-mutations-to-first-and-second-line-regimens-among-ugandan-adults
#19
Ivan Namakoola, Ivan Kasamba, Billy N Mayanja, Patrick Kazooba, Joseph Lutaakome, Fred Lyagoba, Anne A Kapaata, Pontiano Kaleebu, Paula Munderi
BACKGROUND: HIV care programs in resource-limited settings have hitherto concentrated on antiretroviral therapy (ART) access, but HIV drug resistance is emerging. In a cross-sectional study of HIV-positive adults on ART for ≥6 months enrolled into a prospective cohort in Uganda, plasma HIV RNA was measured and genotyped if ≥1000 copies/ml. Identified Drug resistance mutations (DRMs) were interpreted using the Stanford database, 2009 WHO list of DRMs and the IAS 2014 update on DRMs, and examined and tabulated by ART drug classes...
December 23, 2016: BMC Research Notes
https://www.readbyqxmd.com/read/28010168/bayesian-analysis-of-piecewise-growth-mixture-models-with-skew-t-distributions-application-to-aids-studies
#20
Getachew A Dagne, Boubakari Ibrahimou
A major problem in HIV/AIDS studies is the development of drug resistance to antiretroviral (ARV) drug or therapy. Estimating the time at which such drug resistance would develop is usually sought. The goal of this article is to perform this estimation by developing growth mixture models with change-points and skew-t distributions based on longitudinal data. For such data, following ARV treatment, the profile of each subject's viral load tends to follow a 'broken stick' like growth trajectory, indicating multiple phases of decline and increase in viral loads...
December 23, 2016: Journal of Biopharmaceutical Statistics
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