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https://www.readbyqxmd.com/read/28422610/joint-bent-cable-tobit-models-for-longitudinal-and-time-to-event-data
#1
Getachew A Dagne
In this article, we show how to estimate a transition period for the evolvement of drug resistance to antiretroviral (ARV) drug or other related treatments in the framework of developing a Bayesian method for jointly analyzing time to event and longitudinal data. For HIV/AIDS longitudinal data, developmental trajectories of viral loads tend to show a gradual change from a declining trend after initiation of treatment to an increasing trend without an abrupt change. Such characteristics of trajectories are also associated with a time-to-event process...
April 19, 2017: Journal of Biopharmaceutical Statistics
https://www.readbyqxmd.com/read/28403027/candidates-for-inclusion-in-a-universal-antiretroviral-regimen-tenofovir-alafenamide
#2
Dzintars Gotham, Andrew Hill, Anton L Pozniak
PURPOSE OF REVIEW: Tenofovir disoproxil fumarate (TDF) is a standard first-line therapy for HIV. Recently, tenofovir alafenamide (TAF), a different prodrug for the same active moiety, has been approved. In this review, we have conducted a meta-analysis comparing efficacy and safety data for TDF and TAF, to inform a discussion of which drug would be best for a proposed 'universal antiretroviral (ARV) regimen'. RECENT FINDINGS: We identified 10 randomized controlled trials comparing TDF with TAF (6969 patients, 8043 patient-years of follow-up)...
April 11, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28380417/prospects-of-estrogen-receptor-%C3%AE-activation-in-the-treatment-of-castration-resistant-prostate-cancer
#3
Julia Gehrig, Silke Kaulfuß, Hubertus Jarry, Felix Bremmer, Mark Stettner, Peter Burfeind, Paul Thelen
Advanced prostate cancer can develop into castration-resistant prostate cancer (CRPC). This process is mediated either by intratumoral ligand synthesis or by mutations or aberrations of the androgen receptor (AR) or its cofactors. To date, no curative therapy for CRPC is available, as AR-targeted therapies eventually result in the development of resistance. The human prostate cancer cell line VCaP (vertebral cancer of the prostate) overexpresses AR and its splice variants (ARVs) as a mechanism of resistance to androgen-deprivation therapy (ADT) of external and intratumoral origin...
March 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28376825/antiretroviral-therapy-supply-chain-quality-control-and-assurance-in-improving-people-living-with-hiv-therapeutic-outcomes-in-cameroon
#4
M P Ngogang Djobet, David Singhe, Julienne Lohoue, Christopher Kuaban, Jeanne Ngogang, Ernest Tambo
BACKGROUND: Evaluation of medication efficacy and safety is an essential guarantee to successful therapeutic outcome in public health practices. However, larger distribution chain supply in developing countries such as Cameroon is often challenged by counterfeit drugs, poor manufacturing, storage and degradation leading to health and patient adverse consequences. Yet, access to supply chain management in strengthening ARVs quality assurance and outcomes remains poorly documented. More than 53,000 patients have been enrolled on free ARVs medications, but little is documented on quality assurance and validity of safety for affected populations along the supply chain management since 2008...
April 4, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28375551/phenotypic-characterization-of-regulatory-t-cells-from-antiretroviral-na%C3%A3-ve-hiv-1-infected-people
#5
Georgia N Ambada, Claudine E Ntsama, Nadesh N Nji, Loveline N Ngu, Sake N Carole, Abel Lissom, Flaurent T Tchouangeu, Jules Tchadji, Martin Sosso, François-Xavier Etoa, Godwin W Nchinda
Regulatory T cells (Tregs) play a key role in dampening excessive immune activation. However antiretroviral (ARV) naive HIV-1 infection maintains the immune system in a sustained state of activation that could alter both Tregs surface markers and functions. Since Tregs surface markers are directly linked to their functions the overall objective of this study was to determine how ARV naïve HIV infection affects the phenotypic properties of Tregs. Our data showed that in ARV naive HIV-1 infection, Tregs are dominated by effector (CD45RA(+) CD27(-) CCR7(-) CD62L(-) ) and effector memory (CD45RA(-) CD27(-) CCR7(-) CD62L(-) ) cells...
April 4, 2017: Immunology
https://www.readbyqxmd.com/read/28351158/stressful-and-traumatic-life-events-as-disruptors-to-antiretroviral-therapy-adherence
#6
Julie K O'Donnell, Bradley N Gaynes, Stephen R Cole, Andrew Edmonds, Nathan M Thielman, E Byrd Quinlivan, Amy Heine, Rhiddi Modi, Brian W Pence
Stressful and traumatic life events (STLEs) are common among HIV-infected individuals and may affect health behaviors such as adherence to antiretroviral (ARV) therapy, with important implications for treatment outcomes. We examined the association between STLEs and ARV adherence among 289 US-based participants enrolled between 7/1/2010 and 9/1/2013 in a study of depression treatment for HIV-infected patients. Participants received monthly telephone calls to assess STLEs and pill count-based ARV adherence. Inverse probability of observation weighting was combined with multiple imputation to address missing data...
March 28, 2017: AIDS Care
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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...
March 1, 2017: American Journal of Hypertension
https://www.readbyqxmd.com/read/28095307/pre-exposure-prophylaxis-and-antiretroviral-treatment-interventions-with-drug-resistance
#15
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
#16
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 virological failure and at least 2 previously failed ARV regimens from throughout the country were analyzed for the presence of nucleos(t)ide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitor (PI) resistance-associated mutations (RAMs)...
February 21, 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
#17
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
#18
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
#19
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
#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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