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Arv resistance

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https://www.readbyqxmd.com/read/28329343/commonly-transmitted-hiv-1-drug-resistance-mutations-in-reverse-transcriptase-and-protease-in-antiretroviral-treatment-na%C3%A3-ve-patients-do-not-affect-response-to-tenofovir-disoproxil-fumarate-or-tenofovir-alafenamide-containing-regimens
#1
Nicolas A Margot, Pamela Wong, Rima Kulkarni, Kirsten White, Danielle Porter, Michael E Abram, Christian Callebaut, Michael D Miller
Background.: The presence of transmitted drug-resistance mutations (TDRM) in antiretroviral (ARV) treatment-naïve patients can adversely affect the outcome of ARV therapy. Methods.: Resistance testing was conducted in 6704 ARV-naïve subjects predominantly from the U.S. and Europe in 9 Gilead clinical studies from 2000 to 2013. Results.: The presence of TDRM increased during this period (5.2% to 11.4%), primarily driven by non-nucleoside RT inhibitor resistance mutations (NNRTI; 0...
January 30, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28328548/characterization-of-hiv-seroconverters-in-a-tdf-ftc-prep-study-hptn-067-adapt
#2
Mariya V Sivay, Maoji Li, Estelle Piwowar-Manning, Yinfeng Zhang, Sarah E Hudelson, Mark A Marzinke, Rivet K Amico, Andrew Redd, Craig W Hendrix, Peter L Anderson, Kevin Bokoch, Linda Gail-Bekker, Frits van Griensven, Sharon Mannheimer, James P Hughes, Robert Grant, Susan H Eshleman
BACKGROUND: HPTN 067/ADAPT evaluated tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) pre-exposure prophylaxis (PrEP) in women (South Africa) and men who have sex with men (Thailand, US). Participants received once-weekly directly observed TDF/FTC (DOT), and were then randomized to daily, time-driven, or event-driven PrEP. This report describes characterization of 12 HIV seroconversion events in this trial. METHODS: HIV rapid testing was performed at study sites...
March 22, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28302065/lamivudine-dolutegravir-dual-therapy-in-hiv-infected-virologically-suppressed-patients
#3
Franco Maggiolo, Roberto Gulminetti, Layla Pagnucco, Margherita Digaetano, Simone Benatti, Daniela Valenti, Annapaola Callegaro, Diego Ripamonti, Cristina Mussini
BACKGROUND: Little is known about the applicability of dual treatments based on integrase inhibitors. We explored the combination of lamivudine + dolutegravir as an option when switching from standard cART in virologically suppressed patients. METHODS: In this prospective cohort we enrolled patients previously switched to 3TC + DTG who were 18 years or older, with no previous resistance mutations to the used drugs, having a HIV-RNA <50 copies/ml for 6 months or longer, negative for HBsAg and on a stable (>6 months) cART...
March 16, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28235766/sigma1-targeting-to-suppress-aberrant-androgen-receptor-signaling-in-prostate-cancer
#4
Jeffrey D Thomas, Charles G Longen, Halley M Oyer, Nan Chen, Christina M Maher, Joseph M Salvino, Blase Kania, Kelsey N Anderson, William F Ostrander, Karen E Knudsen, Felix J Kim
Suppression of androgen receptor (AR) activity in prostate cancer by androgen depletion or direct AR antagonist treatment, although initially effective, leads to incurable castration resistant prostate cancer (CRPC) via compensatory mechanisms including resurgence of AR and AR splice variant (ARV) signaling. Emerging evidence suggests that Sigma1 (also known as sigma-1 receptor) is a unique chaperone or scaffolding protein that contributes to cellular protein homeostasis. We reported previously that some Sigma1-selective small molecules can be used to pharmacologically modulate protein homeostasis pathways...
February 24, 2017: Cancer Research
https://www.readbyqxmd.com/read/28178281/surveillance-of-hiv-1-pol-transmitted-drug-resistance-in-acutely-and-recently-infected-antiretroviral-drug-na%C3%A3-ve-persons-in-rural-western-kenya
#5
Harris Onywera, David Maman, Seth Inzaule, Erick Auma, Kennedy Were, Harrison Fredrick, Prestone Owiti, Valarie Opollo, Jean-François Etard, Irene Mukui, Andrea A Kim, Clement Zeh
HIV-1 transmitted drug resistance (TDR) is of increasing public health concern in sub-Saharan Africa with the rollout of antiretroviral (ARV) therapy. Such data are, however, limited in Kenya, where HIV-1 drug resistance testing is not routinely performed. From a population-based household survey conducted between September and November 2012 in rural western Kenya, we retrospectively assessed HIV-1 TDR baseline rates, its determinants, and genetic diversity among drug-naïve persons aged 15-59 years with acute HIV-1 infections (AHI) and recent HIV-1 infections (RHI) as determined by nucleic acid amplification test and both Limiting Antigen and BioRad avidity immunoassays, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28105499/cx4945-suppresses-the-growth-of-castration-resistant-prostate-cancer-cells-by-reducing-ar-v7-expression
#6
Chuangzhong Deng, Jieping Chen, Shengjie Guo, Yanjun Wang, Qianghua Zhou, Zaishang Li, Xingping Yang, Xingsu Yu, Zhenfeng Zhang, Fangjian Zhou, Hui Han, Kai Yao
PURPOSE: The aberrant expression of casein kinase 2 (CK2) has been reported to be involved in the tumorigenesis and progression of prostate cancer. The inhibition of CK2 activity represses androgen-dependent prostate cancer cells by attenuating the androgen receptor (AR) signaling pathway. In this study, we examined the effect of CK2 inhibition in castration-resistant prostate cancer (CRPC) cells, in which AR variants (ARVs) play a predominant role. METHODS: A newly synthetic CK2 selective inhibitor CX4945 was utilized to study the effect of CK2 inhibition in CRPC cells by CCK8 assay and colony formation assay...
January 19, 2017: World Journal of Urology
https://www.readbyqxmd.com/read/28104311/comprehensive-profiling-of-the-androgen-receptor-in-liquid-biopsies-from-castration-resistant-prostate-cancer-reveals-novel-intra-ar-structural-variation-and-splice-variant-expression-patterns
#7
Bram De Laere, Pieter-Jan van Dam, Tom Whitington, Markus Mayrhofer, Emanuela Henao Diaz, Gert Van den Eynden, Jean Vandebroek, Jurgen Del-Favero, Steven Van Laere, Luc Dirix, Henrik Grönberg, Johan Lindberg
BACKGROUND: Expression of the androgen receptor splice variant 7 (AR-V7) is associated with poor response to second-line endocrine therapy in castration-resistant prostate cancer (CRPC). However, a large fraction of nonresponding patients are AR-V7-negative. OBJECTIVE: To investigate if a comprehensive liquid biopsy-based AR profile may improve patient stratification in the context of second-line endocrine therapy. DESIGN, SETTING, AND PARTICIPANTS: Peripheral blood was collected from patients with CRPC (n=30) before initiation of a new line of systemic therapy...
January 16, 2017: European Urology
https://www.readbyqxmd.com/read/28096150/hemodynamic-determinants-of-the-short-term-blood-pressure-variability-differential-roles-of-arterial-stiffness-and-wave-reflection
#8
Pai-Feng Hsu, Hao-Min Cheng, Shih-Hsien Sung, Shao-Yuan Chuang, Edward G Lakatta, Frank C P Yin, Pesus Chou, Chen-Huan Chen
BACKGROUND: A high 24-hour ambulatory diastolic (DBP) but not systolic (SBP) blood pressure variability (BPV) is significantly predictive of long-term cardiovascular mortality in untreated hypertensive subjects, independent of office or 24-hour SBP. The present study was aimed to investigate hemodynamic factors that are independently associated with systolic and diastolic BPV from the 24-hour ambulatory blood pressure monitoring (ABPM). METHODS: A cohort of 624 normotensive and 633 untreated hypertensive participants with baseline ABPM was drawn from a community-based survey...
January 17, 2017: American Journal of Hypertension
https://www.readbyqxmd.com/read/28095307/pre-exposure-prophylaxis-and-antiretroviral-treatment-interventions-with-drug-resistance
#9
REVIEW
Komi Afassinou, Faraimunashe Chirove, Keshlan S Govinder
We introduce a model for HIV/AIDS which can be utilized to assess the impact of combining pre-exposure prophylaxis (PrEP) and antiretroviral drugs (ARVs) use interventions (incorporating drug resistance). Mathematical and numerical analyses are carried out to investigate the effects of the combined controls in the presence of PrEP drug resistance. Our results predict a significant decrease in the number of new HIV infections when PrEP and ARVs are concurrently implemented at high levels. The results also reveal that PrEP drug resistance has the potential to slow down or reverse the effects of PrEP, especially at low efficacy levels...
March 2017: Mathematical Biosciences
https://www.readbyqxmd.com/read/28094565/the-decline-in-hiv-1-drug-resistance-in-heavily-antiretroviral-experienced-patients-is-associated-with-optimized-prescriptions-in-a-treatment-roll-out-program-in-mexico
#10
Juan J Calva, Silvana Larrea, Marco A Tapia-Maltos, Mauricio Ostrosky-Frid, Carolina Lara, Pedro Aguilar-Salinas, Héctor Rivera, Juan P Ramírez
A decrease in the rate of acquired antiretroviral (ARV) drug-resistance (ADR) over time has been documented in high-income settings, but data on the determinants of this phenomenon are lacking. We tested the hypothesis that in heavily ARV-experienced patients in the Mexican ARV therapy (ART) roll-out program, the drop in ADR would be associated with changes in ARV drug usage. Genotypic resistance tests obtained from 974 HIV-infected patients with virologic failure and at least 2 previously failed ARV regimens from throughout the country were analyzed for the presence of nRTI, NNRTI and PI resistance-associated mutations (RAMs)...
January 17, 2017: AIDS Research and Human Retroviruses
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
#11
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/28065965/lessons-from-a-seven-year-experience-of-paediatric-hiv-in-pakistan-a-single-centre-experience
#12
Ejaz Ahmed Khan
OBJECTIVE: To describe demographic, clinical and immunologic features of children with human immunodeficiency virus. METHODS: This descriptive study was conducted at the Shifa International Hospital, Islamabad, Pakistan, from 2005 to 2011, and comprised children with human immunodeficiency virus and acquired immune deficiency syndrome. Patients with detailed physical examination and appropriate investigations and those eligible for therapy were included. SPSS 21 was used for data analysis...
January 2017: JPMA. the Journal of the Pakistan Medical Association
https://www.readbyqxmd.com/read/28042144/novel-bet-protein-proteolysis-targeting-chimera-exerts-superior-lethal-activity-than-bromodomain-inhibitor-beti-against-post-myeloproliferative-neoplasm-secondary-s-aml-cells
#13
D T Saenz, W Fiskus, Y Qian, T Manshouri, K Rajapakshe, K Raina, K G Coleman, A P Crew, A Shen, C P Mill, B Sun, P Qiu, T M Kadia, N Pemmaraju, C DiNardo, M-S Kim, A J Nowak, C Coarfa, C M Crews, S Verstovsek, K N Bhalla
The PROTAC (proteolysis-targeting chimera) ARV-825 recruits bromodomain and extraterminal (BET) proteins to the E3 ubiquitin ligase cereblon, leading to degradation of BET proteins, including BRD4. Although the BET-protein inhibitor (BETi) OTX015 caused accumulation of BRD4, treatment with equimolar concentrations of ARV-825 caused sustained and profound depletion (>90%) of BRD4 and induced significantly more apoptosis in cultured and patient-derived (PD) CD34+ post-MPN sAML cells, while relatively sparing the CD34+ normal hematopoietic progenitor cells...
January 31, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28010168/bayesian-analysis-of-piecewise-growth-mixture-models-with-skew-t-distributions-application-to-aids-studies
#14
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
https://www.readbyqxmd.com/read/28006001/detectable-viral-load-in-late-pregnancy-among-women-in-the-rwanda-option-b-pmtct-program-enrollment-results-from-the-kabeho-study
#15
Michelle M Gill, Heather J Hoffman, Emily A Bobrow, Placidie Mugwaneza, Dieudonne Ndatimana, Gilles F Ndayisaba, Cyprien Baribwira, Laura Guay, Anita Asiimwe
There are limited viral load (VL) data available from programs implementing "Option B+," lifelong antiretroviral treatment (ART) to all HIV-positive pregnant and postpartum women, in resource-limited settings. Extent of viral suppression from a prevention of mother-to-child transmission of HIV program in Rwanda was assessed among women enrolled in the Kigali Antiretroviral and Breastfeeding Assessment for the Elimination of HIV (Kabeho) Study. ARV drug resistance testing was conducted on women with VL>2000 copies/ml...
2016: PloS One
https://www.readbyqxmd.com/read/27936098/analysis-of-hiv-diversity-in-hiv-infected-black-men-who-have-sex-with-men-hptn-061
#16
Iris Chen, Gordon Chau, Jing Wang, William Clarke, Mark A Marzinke, Vanessa Cummings, Autumn Breaud, Oliver Laeyendecker, Sheldon D Fields, Sam Griffith, Hyman M Scott, Steven Shoptaw, Carlos Del Rio, Manya Magnus, Sharon Mannheimer, Hong-Van Tieu, Darrell P Wheeler, Kenneth H Mayer, Beryl A Koblin, Susan H Eshleman
BACKGROUND: HIV populations often diversify in response to selective pressures, such as the immune response and antiretroviral drug use. We analyzed HIV diversity in Black men who have sex with men who were enrolled in the HIV Prevention Trials Network 061 study. METHODS: A high resolution melting (HRM) diversity assay was used to measure diversity in six regions of the HIV genome: two in gag, one in pol, and three in env. HIV diversity was analyzed for 146 men who were HIV infected at study enrollment, including three with acute infection and 13 with recent infection (identified using a multi-assay algorithm), and for 21 men who seroconverted during the study...
2016: PloS One
https://www.readbyqxmd.com/read/27890952/a-study-of-antiretroviral-resistance-patterns-in-treatment-experienced-and-naive-human-immunodeficiency-virus-infected-patients
#17
Raj Harjani, Ram Malkani
BACKGROUND: About 10% of the patients had surveillance drug-related mutations for nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) in an Indian study. It was also reported that resistance was maximum for nucleoside reverse transcriptase inhibitors (NRTIs) and minimum for PIs. METHODS: The present study was a cross-sectional assessment of 21 human immunodeficiency virus (HIV)-infected individuals attending a HIV care center in a tertiary care center in Mumbai, Maharashtra, India...
July 2016: Indian Journal of Sexually Transmitted Diseases
https://www.readbyqxmd.com/read/27805572/reporting-on-the-prevalence-of-antiretroviral-drug-resistance-in-a-regional-hiv-population-over-20-years-a-word-of-caution
#18
Victoria C Gill, Tarah Lynch, Soheil Ramazani, Hartmut B Krentz
BACKGROUND: Failure to achieve complete viral suppression with antiretroviral drugs (ARV) may lead to uncontrolled HIV replication, ARV resistance, and negative outcomes. Monitoring and reporting of HIV resistance trends is important but problematic. We examined prevalent resistance rates in a HIV population over 20 years and document how rates may appear to vary dramatically based solely on which parameters are utilized. METHODS: We determined the annual use of GART (genotypic antiretroviral resistance testing) from 1995 to 2014 for all patients receiving HIV care in southern Alberta, Canada, and the presence of resistance mutations in those tested...
November 2, 2016: Antiviral Therapy
https://www.readbyqxmd.com/read/27779200/prevalence-of-integrase-strand-transfer-inhibitors-insti-resistance-mutations-in-taiwan
#19
Sui-Yuan Chang, Pi-Han Lin, Chien-Lin Cheng, Mao-Yuan Chen, Hsin-Yun Sun, Szu-Min Hsieh, Wang-Huei Sheng, Yi-Ching Su, Li-Hsin Su, Shu-Fang Chang, Wen-Chun Liu, Chien-Ching Hung, Shan-Chwen Chang
Antiretroviral therapy containing an integrase strand transfer inhibitor (INSTI) plus two NRTIs has become the recommended treatment for antiretroviral-naive HIV-1-infected patients in the updated guidelines. We aimed to determine the prevalence of INSTI-related mutations in Taiwan. Genotypic resistance assays were performed on plasma from ARV-naïve patients (N = 948), ARV-experienced but INSTI-naive patients (N = 359), and raltegravir-experienced patients (N = 63) from 2006 to 2015. Major INSTI mutations were defined according to the IAS-USA list and other substitutions with a Stanford HIVdb score ≧ 10 to at least one INSTI were defined as minor mutations...
October 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27771050/progress-in-formulation-based-approaches-for-antiretrovirals
#20
Ameya R Kirtane, Robert Langer, Giovanni Traverso
The human immunodeficiency virus has infected millions of people and the epidemic continues to grow rapidly in some parts of the world. Antiretroviral (ARV) therapy has provided improved treatment and prolonged the life expectancy of patients. Moreover, there is growing interest in using ARVs to protect against new infections. Hence, ARVs have emerged as our primary strategy in combating the virus. Unfortunately, several challenges limit the optimal performance of these drugs. First, ARVs often require life-long use and complex dosing regimens...
October 19, 2016: Journal of Pharmaceutical Sciences
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