Clinical research in HIV/AIDS最新文献

Dasatinib: effects on the macrophage phospho proteome with a focus on SAMHD1 and HIV-1 infection. 达沙替尼:对巨噬细胞磷酸化蛋白质组的影响，重点是SAMHD1和HIV-1感染。

Clinical research in HIV/AIDS Pub Date : 2022-01-01

Elizabeth S C P Williams, Matthew A Szaniawski, Laura J Martins, Emily A Innis, José Alcamí, Timothy M Hanley, Adam M Spivak, Mayte Coiras, Vicente Planelles

{"title":"Dasatinib: effects on the macrophage phospho proteome with a focus on SAMHD1 and HIV-1 infection.","authors":"Elizabeth S C P Williams, Matthew A Szaniawski, Laura J Martins, Emily A Innis, José Alcamí, Timothy M Hanley, Adam M Spivak, Mayte Coiras, Vicente Planelles","doi":"","DOIUrl":"","url":null,"abstract":"Macrophages are one of the main cellular targets of human immunodeficiency virus type 1 (HIV-1). Macrophage infection by HIV-1 is inefficient due to the presence of the viral restriction factor sterile alpha motif and histidine aspartic acid domain containing protein 1 (SAMHD1). Ex vivo human monocyte-derived macrophages (MDMs) express SAMHD1 in an equilibrium between active (unphosphorylated) and inactive (phosphorylated) states. We and others have shown that treatment of MDMs with the FDA-approved tyrosine kinase inhibitor, dasatinib, ablates SAMHD1 phosphorylation, thus skewing the balance towards a cellular state that is refractory to HIV-1 infection. We hypothesized that dasatinib inhibits a putative tyrosine kinase that is upstream of SAMHD1. In search for this tyrosine kinase, we probed several candidates and were unable to identify a single target that, when inhibited, was sufficient to explain the dephosphorylation of SAMHD1 we observe upon treatment with dasatinib. On the other hand, we probed the ability of dasatinib to directly inhibit the serine/threonine cyclin dependent kinases 1, 2, 4 and 6 and confirmed that dasatinib directly inhibits these kinases. Therefore, our results show that inhibition of the proximal CDKs 1, 2, 4 and 6 by dasatinib is clearly detectable, leads to blockade of infection by HIV-1, and may be sufficient to explain the activity of dasatinib against SAMHD1 phosphorylation.","PeriodicalId":72627,"journal":{"name":"Clinical research in HIV/AIDS","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9802671/pdf/nihms-1858679.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10062365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Survival Time of People Living With HIV: Systematic Review and Meta-Analysis 艾滋病毒感染者的生存时间:系统回顾和荟萃分析

Clinical research in HIV/AIDS Pub Date : 2022-01-01 DOI: 10.47739/2374-0094/1054

Jean Fernando Sandeski Zuber, Erildo Vicente Muller, C. M. Martins, C. E. Coradassi, Zanoni da Silva Milene

{"title":"Survival Time of People Living With HIV: Systematic Review and Meta-Analysis","authors":"Jean Fernando Sandeski Zuber, Erildo Vicente Muller, C. M. Martins, C. E. Coradassi, Zanoni da Silva Milene","doi":"10.47739/2374-0094/1054","DOIUrl":"https://doi.org/10.47739/2374-0094/1054","url":null,"abstract":"1.1. Introduction: Infection with the human immunodeficiency virus (HIV) is still a global epidemic. More than 40 million people died of acquired immunodeficiency syndrome (AIDS) so far. Antiretroviral treatment (ART), among other health care measures, reversed this fatal outcome. The aim of this study was to analyze the survival time of people living with HIV (PLHIV) through national and international studies in a systematic review with meta-analysis. 1.2. Material and Methods: An electronic search was conducted in three databases PubMed, SciELO and ScienceDirect identify original studies about survival time of PLHIV published until 12/31/2018. 1.3. Results: A total of 2,650 entries were retrieved from which 17 studies met the inclusion criteria. The total number of PLHIV included in these studies was 75,020 people. They were performed in 11 countries, with 35.29% of them in Brazil. The overall mean survival time of PLHIV was 6.36 years (95%CI 5.58-7.14; I2=100%; p<0.001). Survival time of PLHIV was higher for those on ART than for those without treatment: an average of 2.4 years and 1,52, respectively. Survival time of PLHIV also increased with higher educational levels and younger age. 1.4. Conclusion: This systematic review with meta-analysis consolidated the scientific evidence that ART increases survival time of PLHIV.","PeriodicalId":72627,"journal":{"name":"Clinical research in HIV/AIDS","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70880836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Price of Prevention: Cost Effectiveness of Biomedical HIV Prevention Strategies in South Africa. 预防的代价：南非生物医学艾滋病预防战略的成本效益。

Clinical research in HIV/AIDS Pub Date : 2016-01-01 Epub Date: 2016-11-27

Nishila Moodley, Glenda Gray, Melanie Bertram

{"title":"The Price of Prevention: Cost Effectiveness of Biomedical HIV Prevention Strategies in South Africa.","authors":"Nishila Moodley, Glenda Gray, Melanie Bertram","doi":"","DOIUrl":"","url":null,"abstract":"Background: South Africa has the highest global burden of human immunodefciency virus [HIV]. The study compared the cost-effectiveness of individual and combination HIV preventive strategies against the current rollout of ART and possible ART scale-up.Methods: Adolescents attending South African schools in 2012 were included in the semi-Markov running annual cycles. The ART and HIV counseling and testing program [comparator] was weighed against the interventions [viz. HIV vaccine, a dual vaccine strategy [HIV and HPV vaccines], oral pre-exposure prophylaxis [PrEP] and voluntary medical male circumcision [VMMC]; and various combinations thereof. Quality-adjusted life years [QALY] determined changes in HIV associated mortality and infections averted. One-way and probabilistic sensitivity analysis determined parameter uncertainty. Discount rates of 3% with a lifetime horizon [70 years] were applied.Results: Dual vaccination was highly cost-effective strategy [US$ 7 per QALY gained] and averted 29% of new HIV infections. VMMC [US$ 30 per QALY gained] proved more cost-effective than HIV vaccination alone [US$ 93 per QALY gained], though VMMC averted 6% more new infections than the HIV vaccine when considered among male participants. PrEP interventions were the least cost-effective with pharmaceutical and human resource spending driving the costs. Combined dual vaccination and VMMC strategies were a dominant intervention. Strategies involving PrEP were the least cost-effective.Conclusion: VMMC, HIV vaccination and dual vaccination strategies were more cost-effective than any PrEP strategies. A multi-intervention biomedical approach could avert considerable new HIV infections and present a cost-effective use of resources; particularly where large scale multi-interventional randomized controlled trials are absent.","PeriodicalId":72627,"journal":{"name":"Clinical research in HIV/AIDS","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562157/pdf/nihms884981.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35284962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Amyloid beta accumulation in HIV-1 infected brain: the role of altered cholesterol homeostasis. β淀粉样蛋白在HIV-1感染的大脑中积累:改变胆固醇稳态的作用。

Clinical research in HIV/AIDS Pub Date : 2014-01-01 Epub Date: 2014-08-31

Xuesong Chen, Liang Hui, Jonathan D Geiger

{"title":"Amyloid beta accumulation in HIV-1 infected brain: the role of altered cholesterol homeostasis.","authors":"Xuesong Chen, Liang Hui, Jonathan D Geiger","doi":"","DOIUrl":"","url":null,"abstract":"The long-term survival of HIV-1 infected individuals credited to the availability and use of effective antiretroviral therapy (ART) is unfortunately now accompanied by an almost 50% prevalence of HIV-1 associated neurocognitive disorder (HAND). Increasingly, it has been realized that HIV-1 infected people on ART have clinical and pathological observations of Alzheimer's disease (AD)-like manifestations including neurocognitive problems, intraneuronal accumulation of amyloid beta (Aβ) protein, and disturbed synaptic integrity. Part of the current challenge facing the medical community and people living with HIV-1 infection is that the pathogenesis of HAND remains unclear, and little is known about how AD-like pathology is developed as a result of HIV-1 infection and/or long-term ART treatment. Here we discuss the potential role of altered plasma cholesterol homeostasis, a prominent feature of HIV-1 infection, on the development of intraneuronal Aβ accumulation in HIV-1 infected brain. We speculate that elevated plasma LDL cholesterol, once it enters brain parenchyma via an increasingly leaky BBB, can be internalized by neurons via receptor-mediated endocytosis, a process that could promote internalization of amyloid beta precursor protein (AβPP). Unlike brain in situ synthesized apoE-cholesterol, apoB-containing LDL-cholesterol could lead to cholesterol accumulation thus disturbing neuronal endolysosome function and ultimately the accumulation of intraneuronal Aβ in HIV-1 infected brain.","PeriodicalId":72627,"journal":{"name":"Clinical research in HIV/AIDS","volume":"1 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6124677/pdf/nihms-977095.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36477100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0