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Antiretroviral resistance

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https://www.readbyqxmd.com/read/28715978/the-role-of-efflux-pumps-in-tuberculosis-treatment-and-their-promise-as-a-target-in-drug-development-unraveling-the-black-box
#1
Lindsey H M Te Brake, Gerjo J de Knegt, Jurriaan E de Steenwinkel, Teunis J P van Dam, David M Burger, Frans G M Russel, Reinout van Crevel, Jan B Koenderink, Rob E Aarnoutse
Insight into drug transport mechanisms is highly relevant to the efficacious treatment of tuberculosis (TB). Major problems in TB treatment are related to the transport of antituberculosis (anti-TB) drugs across human and mycobacterial membranes, affecting the concentrations of these drugs systemically and locally. Firstly, transporters located in the intestines, liver, and kidneys all determine the pharmacokinetics and pharmacodynamics of anti-TB drugs, with a high risk of drug-drug interactions in the setting of concurrent use of antimycobacterial, antiretroviral, and antidiabetic agents...
July 17, 2017: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/28710808/the-application-of-physiologically-based-pharmacokinetic-modelling-to-assess-the-impact-of-antiretroviral-mediated-drug-drug-interactions-on-piperaquine-antimalarial-therapy-during-pregnancy
#2
Olusola Olafuyi, Michael Coleman, Raj K S Badhan
Antimalarial therapy during pregnancy poses important safety concerns due to potential teratogenicity and maternal physiological and biochemical changes during gestation. Piperaquine (PQ) has gained interest for use in pregnancy in response to increasing resistance towards sulfadoxine-pyrimethamine in sub-Saharan Africa. Co-infection with HIV is common in many developing countries, however, little is known about the impact of anti-retroviral (ARV) mediated drug-drug interaction (DDI) on PQ pharmacokinetics during pregnancy...
July 14, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28692538/metabolic-syndrome-and-obesity-are-the-cornerstones-of-liver-fibrosis-in-hiv-monoinfected-patients-results-of-the-metafib-study
#3
Maud Lemoine, Karine Lacombe, Jean Philippe Bastard, Manuela Sébire, Laurent Fonquernie, Nadia Valin, Soraya Fellahi, Jacqueline Capeau, Pierre-Marie Girard, Jean-Luc Meynard
BACKGROUND: Metabolic syndrome (MetS) and nonalcoholic fatty liver disease (NAFLD) have become a common finding in HIV-infected patients. However, the severity, risk factors and pathogenesis of liver fibrosis in this population have been poorly documented. OBJECTIVES: to assess the impact of MetS on liver fibrosis and analyze the association between MetS, liver fibrosis and markers of adipose tissue and macrophage activation. METHODS: In a matched cohort of HIV-1-monoinfected patients with and without MetS, after exclusion of other causes of liver disease, we assessed liver stiffness measurement (LSM) and measured levels of serum adipokines, HOMA index and soluble CD163 and CD14 as markers of fat, insulin resistance and macrophage/monocyte activation, respectively...
July 7, 2017: AIDS
https://www.readbyqxmd.com/read/28692305/fight-fire-with-fire-gene-therapy-strategies-to-cure-hiv
#4
Jon Huyghe, Sips Magdalena, Linos Vandekerckhove
Human Immunodeficiency Virus (HIV) to date remains one of the most notorious viruses mankind has ever faced. Despite enormous investments in HIV research for more than 30 years an effective cure for HIV has been elusive. Areas covered: Combination antiretroviral therapy (cART) suppresses active viral replication, but is not able to eliminate the virus completely due to stable integration of HIV inside the host genome of infected cells and the establishment of a latent reservoir, that is insensitive to cART...
July 14, 2017: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/28691434/universal-antiretroviral-therapy-for-hiv-infected-children-a-review-of-the-benefits-and-risks-to-consider-during-implementation
#5
Linda Barlow-Mosha, Victor Musiime, Mary-Ann Davies, Andrew J Prendergast, Philippa Musoke, George Siberry, Martina Penazzato
BACKGROUND: The 2016 World Health Organization (WHO) consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection, recommended to start all HIV-infected children on antiretroviral therapy (ART). Here, we explore the possible benefits and risks of implementing universal ART for all HIV-infected children and adolescents and outline some of the key considerations that led to the 2016 revision of WHO guidelines. METHODS: We conducted a review of the published data from 2000 to 2016, to ascertain the clinical and programmatic benefits, as well as the risks of implementing universal ART for all children...
June 27, 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/28688977/prevalence-of-drug-resistance-among-hiv-1-treatment-naive-patients-in-greece-during-2003-2015-transmitted-drug-resistance-is-due-to-onward-transmissions
#6
D Paraskevis, E Kostaki, G Magiorkinis, P Gargalianos, G Xylomenos, E Magiorkinis, M Lazanas, M Chini, G Nikolopoulos, A Skoutelis, V Papastamopoulos, A Antoniadou, A Papadopoulos, M Psichogiou, G L Daikos, M Oikonomopoulou, A Zavitsanou, G Chrysos, V Paparizos, S Kourkounti, H Sambatakou, N V Sipsas, M Lada, P Panagopoulos, E Maltezos, S Drimis, A Hatzakis
BACKGROUND: The prevalence of HIV-1 drug resistance among treatment-naïve patients ranges between 8.3% and 15% in Europe and North America. Previous studies showed that subtypes A and B were the most prevalent in the Greek HIV-1 epidemic. Our aim was to estimate the prevalence of resistance among drug naïve patients in Greece and to investigate the levels of transmission networking among those carrying resistant strains. METHODS: HIV-1 sequences were determined from 3428 drug naïve HIV-1 patients, in Greece sampled during 01/01/2003-30/6/2015...
July 5, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28683357/exercise-improves-cytokine-profile-in-hiv-infected-people-a-randomized-clinical-trial
#7
Rafael Evangelista Pedro, Nadia Candido, Débora Alves Guariglia, Bruno Pereira Melo, Dennis Armando Bertolini, Sidney Barnabé Peres, Solange Marta Franzói de Moraes
PURPOSE: Verify the effects of concurrent training on cytokines in people living with HIV under antiretroviral therapy (ART) treatment. METHODS: This was a blinded, parallel-group, clinical trial, where 49 participants, divided in two groups, either control group or concurrent training group, took part in the intervention. The control group performed recreational activities and concurrent training group participated of 16-week, 3 times per week of heart rate guided-aerobic plus resistance training for major muscular groups...
July 3, 2017: Cytokine
https://www.readbyqxmd.com/read/28679441/hiv-1-genetic-diversity-and-primary-drug-resistance-mutations-before-large-scale-access-to-antiretroviral-therapy-republic-of-congo
#8
Fabien Roch Niama, Nicole Vidal, Halimatou Diop-Ndiaye, Etienne Nguimbi, Gabriel Ahombo, Philippe Diakabana, Édith Sophie Bayonne Kombo, Pembe Issamou Mayengue, Simon-Charles Kobawila, Henri Joseph Parra, Coumba Toure-Kane
BACKGROUND: In this work, we investigated the genetic diversity of HIV-1 and the presence of mutations conferring antiretroviral drug resistance in 50 drug-naïve infected persons in the Republic of Congo (RoC). Samples were obtained before large-scale access to HAART in 2002 and 2004. METHODS: To assess the HIV-1 genetic recombination, the sequencing of the pol gene encoding a protease and partial reverse transcriptase was performed and analyzed with updated references, including newly characterized CRFs...
July 5, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28673572/elimination-of-cancer-stem-cells-and-reactivation-of-latent-hiv-1-via-ampk-activation-common-mechanism-of-action-linking-inhibition-of-tumorigenesis-and-the-potential-eradication-of-hiv-1
#9
Jahahreeh Finley
Although promising treatments are currently in development to slow disease progression and increase patient survival, cancer remains the second leading cause of death in the United States. Cancer treatment modalities commonly include chemoradiation and therapies that target components of aberrantly activated signaling pathways. However, treatment resistance is a common occurrence and recent evidence indicates that the existence of cancer stem cells (CSCs) may underlie the limited efficacy and inability of current treatments to effectuate a cure...
July 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28673254/a-cross-sectional-study-to-evaluate-second-line-virological-failure-and-elevated-bilirubin-as-a-surrogate-for-adherence-to-atazanavir-ritonavir-in-two-urban-hiv-clinics-in-lilongwe-malawi
#10
Dennis Miyoge Ongubo, Robertino Lim, Hannock Tweya, Christopher Chikhosi Stanley, Petros Tembo, Richard Broadhurst, Salem Gugsa, McNeil Ngongondo, Colin Speight, Tom Heller, Sam Phiri, Mina C Hosseinipour
BACKGROUND: Malawi's national antiretroviral therapy program provides atazanavir/ritonavir-based second line regimens which cause concentration-dependent rise in indirect bilirubin. We sought to determine if elevated bilirubin, as a surrogate of atazanavir/ritonavir adherence, can aid in the evaluation of second line virological failure in Malawi. METHODS: We conducted a cross-sectional study of HIV-infected patients ≥15 years who were on boosted protease inhibitor-based second line antiretroviral therapy for at least 6 months in two urban HIV clinics in Lilongwe, Malawi...
July 3, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28664942/darunavir-stands-up-as-preferred-hiv-protease-inhibitor
#11
Josep Mallolas
Current antiretroviral therapy reaches and maintains viral suppression over the years in more than 90% of treated HIV-infected individuals. Although integrase inhibitors are the preferred third agent in antiretroviral therapy in the current guidelines, rilpivirine, a non-nucleoside reverse transcrip- tase inhibitor, and darunavir (DRV), a second-generation protease inhibitor, are the preferred third companion to be used along with a backbone of two nucleos(t)ide reverse transcriptase inhibitors as first-line triple HIV combination treatment...
April 2017: AIDS Reviews
https://www.readbyqxmd.com/read/28663779/antiretroviral-therapy-containing-raltegravir-to-prevent-mother-to-child-transmission-of-hiv-in-infected-pregnant-women
#12
Diego M Cecchini, Marina G Martinez, Laura M Morganti, Claudia G Rodriguez
We conducted a retrospective study in a general hospital in Buenos Aires, Argentina (2009-2015) aimed at evaluating outcomes in HIV-infected pregnant women (HIPW), who were prescribed raltegravir (RAL)-containing antiretroviral therapy (ART). A total of 239 HIPW were enrolled in our study; among them 31 received RAL (12.9%) at different clinical stages: i) intensification (INS): addition of RAL to current ART because of detectable antepartum viral load, 13 (41.9%); ii) late presenter (LP): standard ART + RAL as fourth drug, 15 (48...
May 31, 2017: Infectious Disease Reports
https://www.readbyqxmd.com/read/28659449/early-antiretroviral-therapy-and-potent-second-line-drugs-could-decrease-hiv-incidence-of-drug-resistance
#13
Mingwang Shen, Yanni Xiao, Libin Rong, Lauren Ancel Meyers, Steven E Bellan
Early initiation of antiretroviral therapy (ART) reduces the risk of drug-sensitive HIV transmission but may increase the transmission of drug-resistant HIV. We used a mathematical model to estimate the long-term population-level benefits of ART and determine the scenarios under which earlier ART (treatment at 1 year post-infection, on average) could decrease simultaneously both total and drug-resistant HIV incidence (new infections). We constructed an infection-age-structured mathematical model that tracked the transmission rates over the course of infection and modelled the patients' life expectancy as a function of ART initiation timing...
June 28, 2017: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/28653971/addition-of-etravirine-does-not-enhance-the-initial-decline-of-hiv-1-rna-in-treatment-experienced-patients-receiving-raltegravir
#14
Philippe Flandre, Anne-Geneviève Marcelin, Vincent Calvez
OBJECTIVE: The importance of an early reduction of HIV-1 RNA as a marker for positive longer term outcome is still under debate. We investigate whether antiretroviral-experienced patients receiving raltegravir plus etravirine have a higher early reduction of HIV-1 RNA compared with patients receiving raltegravir. DESIGN: An observational study of treatment-experienced patients. METHODS: The objective is to investigate 349 patients included in a raltegravir resistance study...
August 1, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28652115/longitudinal-trends-of-hiv-drug-resistance-in-a-large-canadian-cohort-1996-2016
#15
Genevieve Rocheleau, Chanson J Brumme, Jeannie Shoveller, Viviane Lima, Richard Harrigan
OBJECTIVES: We aim to identify long-term trends in HIV drug resistance before and after combined antiretroviral therapy (cART) initiation. METHODS: IAS-USA (2015) mutations were identified in 23,271 HIV protease-reverse transcriptase sequences from 6543 treatment naïve British Columbia adults. Participants that started cART between 1996-2014 were followed until April 2016. Equality of proportions test compared the percentage of participants with acquired drug resistance (ADR) or transmitted drug resistance (TDR) in 1996, to those in 2014...
June 23, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28650381/potential-for-immune-driven-viral-polymorphisms-to-compromise-antiretroviral-based-pre-exposure-prophylaxis-for-prevention-of-hiv-1-infection
#16
Hiroyuki Gatanaga, Zabrina L Brumme, Emily Adland, Gustavo Reyes-Terán, Santiago Avila-Rios, Carlos R Mejía-Villatoro, Tsunefusa Hayashida, Takayuki Chikata, Giang Van Tran, Kinh Van Nguyen, Rita I Meza, Elsa Y Palou, Humberto Valenzuela-Ponce, Juan M Pascale, Guillermo Porras-Cortés, Marvin Manzanero, Guinevere Q Lee, Jeffrey N Martin, Mary N Carrington, Mina John, Simon Mallal, Art F Y Poon, Philip Goulder, Masafumi Takiguchi, Shinichi Oka
OBJECTIVE: Long-acting rilpivirine is a candidate for pre-exposure prophylaxis (PrEP) for prevention of HIV-1 infection. However, rilpivirine resistance mutations at reverse transcriptase codon 138 (RT-E138X) occur naturally in a minority of HIV-1-infected persons; in particular those expressing Human Leukocyte Antigen (HLA)-B*18 where RT-E138X arises as an immune escape mutation. We investigate the global prevalence, B*18-linkage and replicative cost of RT-E138X and its regional implications for rilpivirine PrEP...
June 23, 2017: AIDS
https://www.readbyqxmd.com/read/28650246/economic-outcomes-of-first-line-regimen-switching-among-stable-patients-with-hiv
#17
Lisa Rosenblatt, Ami R Buikema, Jerry Seare, Lindsay G S Bengtson, Jonathan Johnson, Feng Cao, Angelina Villasis-Keever
BACKGROUND: Although switching of antiretroviral therapy (ART) is a valid approach for addressing treatment failure in patients with human immunodeficiency virus (HIV), ART changes among those who are well maintained on their current regimens may lead to the development of new side effects or resistance. OBJECTIVE: To examine the effect of first-line regimen switching on subsequent health care utilization and cost among stable HIV patients. METHODS: This was a retrospective claims data study of adult patients with HIV who initiated ART between 2007 and 2013 and had been treated with their initial regimens for at least 6 continuous months...
July 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28649306/decreasing-prevalence-of-transmitted-drug-resistance-among-art-naive-hiv-1-infected-patients-in-iceland-1996-2012
#18
Malik Sallam, Gülşen Özkaya Şahin, Hlynur Indriðason, Joakim Esbjörnsson, Arthur Löve, Anders Widell, Magnus Gottfreðsson, Patrik Medstrand
Introduction: Resistance to antiretroviral drugs can complicate the management of HIV-1 infection and impair control of its spread. The aim of the current study was to investigate the prevalence and transmission of HIV-1 drug resistance among 106 antiretroviral therapy (ART)-naïve patients diagnosed in Iceland (1996-2012). Methods: HIV-1 polymerase sequences were analysed using the Calibrated Population Resistance tool. Domestic spread of transmitted drug resistance (TDR) was investigated through maximum likelihood and Bayesian approaches...
2017: Infection Ecology & Epidemiology
https://www.readbyqxmd.com/read/28641707/analysis-of-transmitted-hiv-drug-resistance-from-2005-to-2015-in-victoria-australia-a-comparison-of-the-old-and-the-new
#19
Jodie D'Costa, Megan Gooey, Nicole Richards, Rizmina Sameer, Elaine Lee, Doris Chibo
Background: Baseline genotyping is part of standard-of-care treatment. It reveals that transmitted drug resistance (TDR) continues to be important for the management of HIV infection. Attention is typically focused on determining whether resistance to the protease inhibitors (PI) and reverse transcriptase inhibitors (RTI) occurs. However, the increasing use of integrase inhibitors (INIs) raises a concern that TDR to this class of antiretroviral drug may also occur. Methods: PI and RTI drug resistance genotyping was performed on blood samples collected between 2005 and 2015 from 772 treatment-naïve Victorian patients infected with HIV within the previous 12 months...
June 23, 2017: Sexual Health
https://www.readbyqxmd.com/read/28628529/appraising-viral-load-thresholds-and-adherence-support-recommendations-in-the-world-health-organization-guidelines-for-detection-and-management-of-virologic-failure
#20
Suzanne M McCluskey, Yap Boum, Nicholas Musinguzi, Jessica E Haberer, Jeffrey N Martin, Peter W Hunt, Vincent C Marconi, David R Bangsberg, Mark J Siedner
BACKGROUND: The World Health Organization defines HIV virologic failure as two consecutive viral loads >1,000 copies/mL, measured 3-6 months apart with interval adherence support. We sought to empirically evaluate these guidelines using data from an observational cohort. SETTING: The Uganda AIDS Rural Treatment Outcomes study observed adults with HIV in southwestern Uganda from the time of antiretroviral therapy (ART) initiation, and monitored adherence with electronic pill bottles...
June 15, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
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