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HIV Modeling

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https://www.readbyqxmd.com/read/28931091/mt-cell-responses-targeting-hiv-nef-uniquely-correlate-with-infected-cell-frequencies-after-long-term-antiretroviral-therapy
#1
Allison S Thomas, Kimberley L Jones, Rajesh T Gandhi, Deborah K McMahon, Joshua C Cyktor, Dora Chan, Szu-Han Huang, Ronald Truong, Alberto Bosque, Amanda B Macedo, Colin Kovacs, Erika Benko, Joseph J Eron, Ronald J Bosch, Christina M Lalama, Samuel Simmens, Bruce D Walker, John W Mellors, R Brad Jones
HIV-specific CD8+ T-cell responses limit viral replication in untreated infection. After the initiation of antiretroviral therapy (ART), these responses decay and the infected cell population that remains is commonly considered to be invisible to T-cells. We hypothesized that HIV antigen recognition may persist in ART-treated individuals due to low-level or episodic protein expression. We posited that if persistent recognition were occurring it would be preferentially directed against the early HIV gene products Nef, Tat, and Rev as compared to late gene products, such as Gag, Pol, and Env, which have higher barriers to expression...
September 20, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28931083/in-vivo-virulence-of-mhc-adapted-aids-virus-serially-passaged-through-mhc-mismatched-hosts
#2
Sayuri Seki, Takushi Nomura, Masako Nishizawa, Hiroyuki Yamamoto, Hiroshi Ishii, Saori Matsuoka, Teiichiro Shiino, Hironori Sato, Kazuta Mizuta, Hiromi Sakawaki, Tomoyuki Miura, Taeko K Naruse, Akinori Kimura, Tetsuro Matano
CD8+ T-cell responses exert strong suppressive pressure on HIV replication and select for viral escape mutations. Some of these major histocompatibility complex class I (MHC-I)-associated mutations result in reduction of in vitro viral replicative capacity. While these mutations can revert after viral transmission to MHC-I-disparate hosts, recent studies have suggested that these MHC-I-associated mutations accumulate in populations and make viruses less pathogenic in vitro. Here, we directly show an increase in the in vivo virulence of an MHC-I-adapted virus serially-passaged through MHC-I-mismatched hosts in a macaque AIDS model despite a reduction in in vitro viral fitness...
September 20, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28931037/assessment-of-renal-function-in-routine-care-of-people-living-with-hiv-on-art-in-a-resource-limited-setting-in-urban-zambia
#3
Andreas Deckert, Florian Neuhann, Christina Klose, Thomas Bruckner, Claudia Beiersmann, John Haloka, Mannie Nsofwa, Greg Banda, Maik Brune, Helmut Reutter, Dietrich Rothenbacher, Martin Zeier
INTRODUCTION: Data on renal impairment in sub-Saharan Africa (SSA) remains scarce, determination of renal function is not part of routine assessments. We evaluated renal function and blood pressure in a cohort of people living with HIV (PLWH) on antiretroviral treatment (ART) in the Renal Care Zambia project (ReCaZa). METHODS: Using routine data from an HIV outpatient clinic from 2011-2013, we retrospectively estimated the glomerular filtration rate (eGFR, CKD-Epi formula) of PLWH on ART in Lusaka, Zambia...
2017: PloS One
https://www.readbyqxmd.com/read/28926411/lower-mitochondrial-dna-and-altered-mitochondrial-fuel-metabolism-in-hiv-exposed-uninfected-infants-in-cameroon
#4
Jennifer Jao, Kathleen M Powis, Brian Kirmse, Chunli Yu, Fanny Epie, Emmanuel Nshom, Elaine J Abrams, Rhoda S Sperling, Derek Leroith, Mitchell E Geffner, Irwin J Kurland, Hélène C F Côté
OBJECTIVE: Evaluate blood mitochondrial DNA (mtDNA) content in HIV/antiretroviral (ARV)-exposed uninfected (HEU) vs. HIV-unexposed uninfected (HUU) infants and investigate differences in mitochondrial-related metabolites by exposure group. DESIGN: We enrolled a prospective cohort of HIV-infected and -uninfected pregnant woman/infant pairs in Cameroon. METHODS: Dried blood spot mtDNA:nuclear DNA ratio was measured by monochrome multiplex qPCR in HEU infants exposed to in utero ARVs and postnatal zidovudine (HEU-Z) or nevirapine (HEU-N), and in HUU infants at 6 weeks of life...
September 18, 2017: AIDS
https://www.readbyqxmd.com/read/28926409/effects-of-concurrent-exposure-to-antiretrovirals-and-cotrimoxazole-prophylaxis-among-hiv-exposed-uninfected-infants
#5
Alexander C Ewing, Caroline C King, Jeffrey B Wiener, Charles S Chasela, Michael G Hudgens, Debbie Kamwendo, Gerald Tegha, Mina C Hosseinipour, Denise J Jamieson, Charles Van der Horst, Athena P Kourtis
BACKGROUND: Given the potential of Cotrimoxazole preventive therapy (CPT) to prevent bacterial and malarial infections in HIV exposed, uninfected (HEU) infants, it is important to evaluate the effects of its concurrent use with ARV agents that have overlapping toxicity profiles. METHODS: We used data from the Breastfeeding, Antiretrovirals and Nutrition-BAN study (2004-2010) to evaluate the association of CPT and ARV with hematologic measures (hemoglobin, neutrophil, and alanine aminotransferase levels) from 6 to 48 weeks of age in 2,006 HEU infants in Lilongwe, Malawi...
September 18, 2017: AIDS
https://www.readbyqxmd.com/read/28926407/dysfunctional-hdl-from-hiv-individuals-promotes-monocyte-derived-foam-cell-formation-in-vitro
#6
Thomas A Angelovich, Anna C Hearps, Michael N Oda, Mark S Borja, Diana Huynh, Stefanie Homann, Anthony Jaworowski, Theodoros Kelesidis
OBJECTIVE: The role of HDL function in HIV-related atherosclerotic cardiovascular disease (CVD) is unclear. HDLs isolated from HIV+ [HIV(+)HDL] and HIV-uninfected individuals (HDL) were assessed for HDL function and ability to promote monocyte-derived foam cell formation (MDFCF) (a key event in HIV-related CVD) ex vivo. DESIGN/METHODS: Using an established in vitro model of atherogenesis and plasma samples from an established cross-sectional study of virologically-suppressed HIV+ males on stable effective antiretroviral therapy (ART) and with low CVD risk (median age: 42 years; n = 10), we explored the impact of native HDL [HIV(+)HDL] on MDFCF...
September 18, 2017: AIDS
https://www.readbyqxmd.com/read/28926405/elevated-ischemic-stroke-risk-among-women-living-with-hiv-infection
#7
Felicia C Chow, Susan Regan, Markella V Zanni, Sara E Looby, Cheryl D Bushnell, James B Meigs, Steven K Grinspoon, Steve K Feske, Virginia A Triant
OBJECTIVE: To determine if the greater risk of ischemic stroke observed in women living with HIV infection (WLWH) compared with HIV-uninfected women persists after accounting for both traditional and sex-specific stroke risk factors. METHODS: We performed an observational cohort study of WLWH (n = 1,214) and demographics-matched HIV-uninfected women (n = 12,041) seen between 1996 and 2011 at two tertiary care hospitals in Boston. We used Cox proportional hazards regression analyses to model time to ischemic stroke, adjusting first for demographics and traditional stroke risk factors and then for sex-specific stroke risk factors, including menopause and estrogen use...
September 18, 2017: AIDS
https://www.readbyqxmd.com/read/28926404/metabolic-health-across-the-body-mass-index-spectrum-in-hiv-infected-and-hiv-uninfected-men
#8
Jordan E Lake, Xiuhong Li, Frank J Palella, Kristine M Erlandson, Dorothy Wiley, Lawrence Kingsley, Lisa P Jacobson, Todd T Brown
OBJECTIVES: In the general population, metabolic health (MH) often declines as body mass index (BMI) increases. However, some obese individuals maintain MH. HIV and antiretroviral therapy (ART) have been associated with metabolic disturbances. We hypothesized that HIV-infected (HIV+) men on suppressive ART experience less MH than HIV-uninfected (HIV-) men across all BMI categories. DESIGN/METHODS: In a cross-sectional analysis of 1018 HIV+ and 1092 HIV- men enrolled in the Multicenter AIDS Cohort Study, Poisson regression with robust variance determined associations between HIV serostatus and MH prevalence (defined as meeting 2 of 5 NCEP/ATP III metabolic syndrome criteria), adjusting for age, race, BMI category, smoking and hepatitis C virus infection status...
September 18, 2017: AIDS
https://www.readbyqxmd.com/read/28926403/pathways-from-sexual-stigma-to-incident-hiv-and-sexually-transmitted-infections-among-nigerian-men-who-have-sex-with-men
#9
Cristina Rodriguez-Hart, Rebecca G Nowak, Rashelle Musci, Danielle German, Ifeanyi Orazulike, Blessing Kayode, Hongjie Liu, Oye Gureje, Trevor A Crowell, Stefan Baral, Man Charurat
OBJECTIVES: Sexual stigma affecting men who have sex with men (MSM) in Nigeria may be an important driver of HIV and other sexually transmitted infections (STIs), but potential mechanisms through which this occurs are not well understood. This study assessed the contributions of suicidal ideation and sexual risk behaviors to causal pathways between stigma and HIV/STIs. DESIGN: Data were collected from the TRUST/RV368 Study, a prospective cohort of 1,480 MSM from Abuja and Lagos, Nigeria...
September 18, 2017: AIDS
https://www.readbyqxmd.com/read/28926397/time-to-first-positive-hiv-1-dna-pcr-may-differ-with-antiretroviral-regimen-in-infants-infected-with-non-b-subtype-hiv-1
#10
Raji Balasubramanian, Mary Glenn Fowler, Kenneth Dominguez, Shahin Lockman, Pat A Tookey, Nicole Ngo Giang Huong, Steven Nesheim, Michael D Hughes, Marc Lallemant, Jennifer Tosswill, Nathan Shaffer, Gayle Sherman, Paul Palumbo, David E Shapiro
OBJECTIVE: To evaluate the association of type and timing of prophylactic maternal and infant antiretroviral regimen with time to first positive HIV-1 DNA polymerase chain reaction (PCR) test, in non-breastfed HIV-infected infants from populations infected predominantly with HIV-1 non-B subtype virus. DESIGN: Analysis of combined data on non-breastfed HIV-infected infants from prospective cohorts in Botswana, Thailand and the United Kingdom (n = 405). METHODS: Parametric models appropriate for interval-censored outcomes estimated the time to first positive PCR according to maternal or infant antiretroviral regimen category and timing of maternal antiretroviral initiation, with adjustment for covariates...
September 18, 2017: AIDS
https://www.readbyqxmd.com/read/28925587/lessons-learned-from-the-development-and-parameterization-of-a-computer-simulation-model-to-evaluate-task-modification-for-healthcare-providers
#11
Parastu Kasaie, W David Kelton, Rachel M Ancona, Michael J Ward, Craig M Froehle, Michael S Lyons
Computer simulation is a highly advantageous method for understanding and improving healthcare operations with a wide variety of possible applications. Most computer-simulation studies in emergency medicine have sought to improve allocation of resources to meet demand, or to assess the impact of hospital and other system policies on emergency department (ED) throughput. These models have enabled essential discoveries that can be used to improve the general structure and functioning of EDs. Theoretically, computer simulation could also be used to examine the impact of adding or modifying specific provider tasks...
September 19, 2017: Academic Emergency Medicine: Official Journal of the Society for Academic Emergency Medicine
https://www.readbyqxmd.com/read/28924551/identification-and-characterization-of-loop7-motif-and-its-role-in-regulating-biological-function-of-human-apobec3g-through-molecular-modeling-and-biological-assay
#12
Congjie Zhai, Ling Ma, Zhixin Zhang, Jiwei Ding, Jing Wang, Yongxin Zhang, Xiaoyu Li, Fei Guo, Liyan Yu, Jinming Zhou, Shan Cen
Human APOBEC3G (hA3G) is a cytidine deaminase which inhibits HIV-1 replication. The HIV-1 accessory protein viral infectivity factor (Vif) counteracts with hA3G by targeting it for proteasomal degradation. In this work, we constructed and optimized molecular models of the hA3G dimer and the hA3G-Vif complex. The molecular modeling study revealed that the loop7 motif of hA3G appears on the interfaces of both the hA3G-Vif complex and the hA3G dimer. Biochemical analysis provided evidence suggesting that binding of Vif to hA3G results in steric blocking of hA3G dimerization, implying that monomeric hA3G serves as a substrate for Vif-mediated degradation...
September 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28923862/antiviral-activity-of-bictegravir-and-cabotegravir-against-integrase-inhibitor-resistant-sivmac239-and-hiv-1
#13
Said A Hassounah, Ahmad Alikhani, Maureen Oliveira, Simrat Bharaj, Ruxandra-Ilinca Ibanescu, Nathan Osman, Hong-Tao Xu, Bluma G Brenner, Thibault Mesplède, Mark A Wainberg
Animal models are essential to study novel antiretroviral drugs, resistance-associated mutations (RAMs), and treatment strategies. Bictegravir (BIC) is a novel potent integrase (IN) strand transfer inhibitor (INSTI) that has shown promising results against HIV-1 infection in vitro and in vivo and against clinical isolates with resistance against INSTIs. BIC has a higher genetic barrier to the development of resistance than two clinically approved INSTIs termed raltegravir and elvitegravir. Another clinically approved INSTI, dolutegravir (DTG) also possesses a high genetic barrier to resistance while a fourth compound termed cabotegravir (CAB) is currently in late phases of clinical development...
September 18, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28922356/mathematical-modeling-and-quantitative-analysis-of-hiv-1-gag-trafficking-and-polymerization
#14
Yuewu Liu, Xiufen Zou
Gag, as the major structural protein of HIV-1, is necessary for the assembly of the HIV-1 sphere shell. An in-depth understanding of its trafficking and polymerization is important for gaining further insights into the mechanisms of HIV-1 replication and the design of antiviral drugs. We developed a mathematical model to simulate two biophysical processes, specifically Gag monomer and dimer transport in the cytoplasm and the polymerization of monomers to form a hexamer underneath the plasma membrane. Using experimental data, an optimization approach was utilized to identify the model parameters, and the identifiability and sensitivity of these parameters were then analyzed...
September 18, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28920929/structural-investigation-of-nucleophosmin-interaction-with-the-tumor-suppressor-fbw7%C3%AE
#15
A Di Matteo, M Franceschini, A Paiardini, A Grottesi, S Chiarella, S Rocchio, C Di Natale, D Marasco, L Vitagliano, C Travaglini-Allocatelli, L Federici
Nucleophosmin (NPM1) is a multifunctional nucleolar protein implicated in ribogenesis, centrosome duplication, cell cycle control, regulation of DNA repair and apoptotic response to stress stimuli. The majority of these functions are played through the interactions with a variety of protein partners. NPM1 is frequently overexpressed in solid tumors of different histological origin. Furthermore NPM1 is the most frequently mutated protein in acute myeloid leukemia (AML) patients. Mutations map to the C-terminal domain and lead to the aberrant and stable localization of the protein in the cytoplasm of leukemic blasts...
September 18, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28919824/strengthening-participation-by-young-women-sex-workers-in-hiv-programs-reflections-on-a-study-from-bangkok-thailand
#16
Cath Conn, Kristel Modderman, Shoba Nayar
BACKGROUND: Participation is an accepted means of increasing the effectiveness of public health programs, and as such, it is considered an important component of HIV interventions targeting at-risk youth. The situation of young women sex workers in Thailand is alarming on many fronts, including that of HIV risk. As a result, HIV programs in Thailand are the key interventions undertaken in relation to young women sex workers' health. A small-scale study used semistructured interviews to explore the participation reports of five young women sex workers, as well as the related views of two community support workers, who lived and worked in Bangkok, Thailand...
2017: International Journal of Women's Health
https://www.readbyqxmd.com/read/28919433/the-p2x7-receptor-in-dorsal-root-ganglia-is-involved-in-hiv-gp120-associated-neuropathic-pain
#17
Bing Wu, Lichao Peng, Jinyan Xie, Lifang Zou, Qicheng Zhu, Huaide Jiang, Zhihua Yi, Shouyu Wang, Yun Xue, Yun Gao, Guilin Li, Shuangmei Liu, Chunping Zhang, Guodong Li, Shangdong Liang, Huangui Xiong
Human immunodeficiency virus (HIV)-associated neuropathic pain is common, and studies have shown that HIV envelope glycoprotein 120 (gp120) can directly stimulate primary sensory afferent neurons causing hyperalgesia. The P2X7 receptor in the dorsal root ganglia (DRG) is involved in pain transmission and is closely related to the inflammatory and immune response. In this study, we aimed to explore the role of the P2X7 receptor in gp120-induced neuropathic pain using a rat model specific for this type of pain...
September 14, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28919116/global-regional-and-national-age-sex-specific-mortality-for-264-causes-of-death-1980-2016-a-systematic-analysis-for-the-global-burden-of-disease-study-2016
#18
(no author information available yet)
BACKGROUND: Monitoring levels and trends in premature mortality is crucial to understanding how societies can address prominent sources of early death. The Global Burden of Disease 2016 Study (GBD 2016) provides a comprehensive assessment of cause-specific mortality for 264 causes in 195 locations from 1980 to 2016. This assessment includes evaluation of the expected epidemiological transition with changes in development and where local patterns deviate from these trends. METHODS: We estimated cause-specific deaths and years of life lost (YLLs) by age, sex, geography, and year...
September 16, 2017: Lancet
https://www.readbyqxmd.com/read/28919115/global-regional-and-national-under-5-mortality-adult-mortality-age-specific-mortality-and-life-expectancy-1970-2016-a-systematic-analysis-for-the-global-burden-of-disease-study-2016
#19
(no author information available yet)
BACKGROUND: Detailed assessments of mortality patterns, particularly age-specific mortality, represent a crucial input that enables health systems to target interventions to specific populations. Understanding how all-cause mortality has changed with respect to development status can identify exemplars for best practice. To accomplish this, the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) estimated age-specific and sex-specific all-cause mortality between 1970 and 2016 for 195 countries and territories and at the subnational level for the five countries with a population greater than 200 million in 2016...
September 16, 2017: Lancet
https://www.readbyqxmd.com/read/28918477/in-vitro-inhibition-of-hiv-1-replication-in-autologous-cd4-t-cells-indicates-viral-containment-by-multifactorial-mechanisms
#20
Ting Tu, Jianbo Zhan, Danlei Mou, Wei Li, Bin Su, Tong Zhang, Tao Li, Ning Li, Hao Wu, Cong Jin, Huabiao Chen
HIV-1-specific cytotoxic T lymphocytes (CTLs) and neutralizing antibodies (NAbs) are present during chronic infection, but the relative contributions of these effector mechanisms to viral containment remain unclear. Here, using an in vitro model involving autologous CD4(+) T cells, primary HIV-1 isolates, HIV-1-specific CTLs, and neutralizing monoclonal antibodies, we show that b12, a potent and broadly neutralizing monoclonal antibody to HIV-1, was able to block viral infection when preincubated with virus prior to infection, but was much less effective than CTLs at limiting virus replication when added to infected cell cultures...
September 15, 2017: Virologica Sinica
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