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Retroviral therapy

Yan-Yi Wang, Shan Ma, Qingyong Chen, Demin Jiao, Yong Yang
Current in vivo selections for hematopoietic stem cell (HSC)-based gene therapy are drug dependent and not without risk of cytotoxicity or tumorigenesis. We developed a new in vivo selection system with the non-phosphorylatable Bcl2 mutant Bcl2T69A/S70A/S87A (Bcl2AAA ), which makes in vivo selection drug independent and without risk of cytotoxicity or tumorigenesis. We demonstrated in HSC-transplanted mice that Bcl2AAA facilitated efficient in vivo selection in the absence of any exogenously applied drugs under both myeloablative and non-myeloablative conditioning...
March 9, 2018: Gene Therapy
Nidaa Mikail, Mathieu Sinigaglia, Fabien Hyafil
Important progresses in the management of patients with human immunodeficiency virus, in particular the advent of new anti-retroviral therapies (ART), have turned this rapidly fatal condition into a controllable chronic disease with a life expectancy that approaches the one from the general population. Cardiovascular diseases have now become one of the leading causes of non-HIV-related mortality in this population. Several factors including the presence of HIV in the vascular wall and the development of dyslipidemia and alteration in body fat distribution under ART might play a role the progression of atherosclerosis in HIV-infected patients...
March 8, 2018: Journal of Nuclear Cardiology: Official Publication of the American Society of Nuclear Cardiology
Priyanka Chauhan, Wen S Sheng, Shuxian Hu, Sujata Prasad, James R Lokensgard
BACKGROUND: Peripheral neuropathy is currently the most common neurological complication in HIV-infected individuals, occurring in 35-50% of patients undergoing combination anti-retroviral therapy. Data have shown that distal symmetric polyneuropathy develops in mice by 6 weeks following infection with the LP-BM5 retrovirus mixture. Previous work from our laboratory has demonstrated that glial cells modulate antiviral T-cell effector responses through the programmed death (PD)-1: PD-L1 pathway, thereby limiting the deleterious consequences of unrestrained neuroinflammation...
March 5, 2018: Journal of Neuroinflammation
Lu Yang, Fang Niu, Honghong Yao, Ke Liao, Xufeng Chen, Yeonhee Kook, Rong Ma, Guoku Hu, Shilpa Buch
Chronic neuroinflammation still remains a common underlying feature of HIV-infected patients on combined anti-retroviral therapy (cART). Previous studies have reported that despite near complete suppression of virus replication by cART, cytotoxic viral proteins such as HIV trans-activating regulatory protein (Tat) continue to persist in tissues such as the brain and the lymph nodes, thereby contributing, in part, to chronic glial activation observed in HIV-associated neurological disorders (HAND). Understanding how the glial cells cross talk to mediate neuropathology is thus of paramount importance...
March 1, 2018: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
Khem Narayan Pokhrel, Kalpana Gaulee Pokhrel, Sanjeev Raj Neupane, Vidya Dev Sharma
BACKGROUND: People living with Human Immunodeficiency Virus (HIV) often suffer from alcohol-use disorders resulting in their poor health and treatment outcomes. Little is known about the association of harmful alcohol drinking with their adherence to anti-retroviral therapy (ART) and health-related quality of life (QOL) in low-resource settings. OBJECTIVE: This study aimed to investigate associations between harmful alcohol drinking, adherence to ART and health-related QOL in HIV-positive people, stratified by gender, in Nepal...
2018: Global Health Action
James Ogunmodede, Philip Kolo, Ibraheem Katibi, Ayodele Omotoso
Background: HAART has improved survival of HIV patients. Its contribution to the development of new cardiovascular abnormalities has generated much interest. This study aimed at determining the prevalence of QTc prolongation among HIV patients and determining the influence if any of the use of HAART on the QTc and on the risk of having QTc prolongation. Materials and Methods: One hundred and fifty HIV positive subjects comprising 76 HIV positive subjects on HAART (Group A), 74 who were HAART- naïve (Group B), and 150 age and sex-matched healthy controls (Group C) were studied...
November 2017: Ethiopian Journal of Health Sciences
Myung-Ku Kim, Chul-Won Ha, Yong In, Sung-Do Cho, Eui-Sung Choi, Jeong-Ku Ha, Ju-Hong Lee, Jae-Doo Yoo, Seong-Il Bin, Choong-Hyeok Choi, Hee-Soo Kyung, Myung-Chul Lee
OBJECTIVE: To test the clinical efficacy of TissueGene-C (TG-C), a cell and gene therapeutic for osteoarthritis consisting of non-transformed and transduced chondrocytes (3:1), retrovirally transduced to overexpress TGF-β1. DESIGN: We randomly assigned 163 with knee osteoarthritis to receive intra-articular TG-C or placebo in Kellgren-Lawrence grade 3 patients for clinical trial. Primary efficacy measures included criteria for subjective assessment by International Knee Documentation Committee (IKDC) and pain severity by Visual Analog Scale (VAS) for 52 weeks...
February 27, 2018: Human Gene Therapy. Clinical Development
Sumona Chaudhury, Ellen Hertzmark, Aisa Muya, David Sando, Nzovu Ulenga, Lameck Machumi, Donna Spiegelman, Wafaie W Fawzi
INTRODUCTION: Global scale up of anti-retroviral therapy (ART) has led to expansion of HIV treatment and prevention across sub-Saharan Africa. However, age and gender-specific disparities persist leading to failures in fulfillment of Sustainability Development Goals, including SDG3 (achieving healthy lives and wellbeing for all, at all ages) and SDG5 (gender equality). We assessed ART initiation and adherence, loss to follow-up, all-cause death and early death, according to SDG3 and SDG5 indicators among a cohort of HIV-infected children and adolescents enrolled in care in Dar-es-Salaam, Tanzania METHODS: SDG3 indicators included young (<5 years) and older paediatric children (5 to <10 years), early adolescent (10 to <15 years) and late adolescent (15 to <20 years) age group divisions and the SDG5 indicator was gender...
February 2018: Journal of the International AIDS Society
Animut Alebel, Fasil Wagnew, Cheru Tesema, Getiye Dejenu Kibret, Pammla Petrucka, Setegn Eshite
BACKGROUND: The relationship between undernutrition and HIV is bidirectional, ultimately contributing to quality of life and survival of affected individuals. Ethiopia is a sub-Saharan nation influenced by both undernutrition and HIV. In Ethiopia, although individuals are often dually impacted, the effect of undernutrition on the survival of HIV positive children on anti-retroviral therapy (ART) has not been well investigated. Therefore, this study assessed the effect of undernutrition on survival rates of HIV positive children on ART in Amhara Regional State of Ethiopia...
February 27, 2018: Italian Journal of Pediatrics
Javed Butler, Andreas P Kalogeropoulos, Kevin J Anstrom, Priscilla Y Hsue, Raymond J Kim, Rebecca Scherzer, Sanjiv J Shah, Svati H Shah, Eric J Velazquez, Adrian F Hernandez, Patrice Desvigne-Nickens, Eugene Braunwald
Antiretroviral therapy (ART) has been associated with a shift in the epidemiology of HIV-associated cardiomyopathy from a phenotype of primarily left ventricular (LV) systolic dysfunction to LV diastolic dysfunction (DD). Patients with HIV receiving ART have higher rates of DD when compared to age-matched controls and develop DD at a younger age. However, little is known about the natural history and pathogenesis of DD in virally suppressed HIV-infected patients. Current evidence suggests that immune processes modulate the risk for cardiac involvement in HIV-infected persons...
February 23, 2018: Journal of Cardiac Failure
Pavlína Ptáčková, Jan Musil, Martin Štach, Petr Lesný, Šárka Němečková, Vlastimil Král, Milan Fábry, Pavel Otáhal
BACKGROUND AIMS: Clinical-grade chimeric antigenic receptor (CAR)19 T cells are routinely manufactured by lentiviral/retroviral (LV/RV) transduction of an anti-CD3/CD28 activated T cells, which are then propagated in a culture medium supplemented with interleukin (IL)-2. The use of LV/RVs for T-cell modification represents a manufacturing challenge due to the complexity of the transduction approach and the necessity of thorough quality control. METHODS: We present here a significantly improved protocol for CAR19 T-cell manufacture that is based on the electroporation of peripheral blood mononuclear cells with plasmid DNA encoding the piggyBac transposon/transposase vectors and their cultivation in the presence of cytokines IL-4, IL-7 and IL-21...
February 20, 2018: Cytotherapy
Ewurama D A Owusu, Samson K Djonor, Charles A Brown, Martin P Grobusch, Petra F Mens
BACKGROUND: Plasmodium falciparum, the most dominant species in sub-Saharan Africa, causes the most severe clinical malaria manifestations. In resource-limited Ghana, where malaria and HIV geographically overlap, histidine-rich protein 2 (HRP2)-based rapid diagnostic test (RDT) is a faster, easier and cheaper alternative to clinical gold standard light microscopy. However, mutations in parasite hrp2 gene may result in missed infections, which have severe implications for malaria control...
February 23, 2018: Malaria Journal
Maliha Naseer, Francis E Dailey, Alhareth Al Juboori, Sami Samiullah, Veysel Tahan
Diseases of the liver and biliary tree have been described with significant frequency among patients with human immunodeficiency virus (HIV), and its advanced state, acquired immunodeficiency syndrome (AIDS). Through a variety of mechanisms, HIV/AIDS has been shown to affect the hepatic parenchyma and biliary tree, leading to liver inflammation and biliary strictures. One of the potential hepatobiliary complications of this viral infection is AIDS cholangiopathy, a syndrome of biliary obstruction and liver damage due to infection-related strictures of the biliary tract...
February 21, 2018: World Journal of Gastroenterology: WJG
Olumide Abiodun, Ismail Lawal, Christopher Omokanye
HIV is now regarded as a chronic disease because of the availability of treatment. However, it is not well known if there are differences (clinically and in magnitude) between the mental health status of PLHIV and people living with other chronic diseases. The aim of this study was to compare the mental health status of patients attending antiretroviral clinics to patients attending diabetes clinics at tertiary hospitals in Ogun State, Nigeria. A comparative hospital-based cross-sectional study of mental distress among 639 HIV-positive and 639 diabetic patients was carried out...
February 19, 2018: AIDS Care
Nadine Teichweyde, Lara Kasperidus, Sebastian Carotta, Valerie Kouskoff, Georges Lacaud, Peter A Horn, Stefan Heinrichs, Hannes Klump
Generation of hematopoietic stem cells (HSCs) from pluripotent stem cells, in vitro, holds great promise for regenerative therapies. Primarily, this has been achieved in mouse cells by overexpression of the homeotic selector protein HOXB4. The exact cellular stage at which HOXB4 promotes hematopoietic development, in vitro, is not yet known. However, its identification is a prerequisite to unambiguously identify the molecular circuits controlling hematopoiesis, since the activity of HOX proteins is highly cell and context dependent...
February 15, 2018: Stem Cell Reports
Umesh Chandra Halder
Human immunodeficiency virus (HIV) still poses enigmatic threats to human life. This virus has mastered in bypassing anti retroviral therapy leading to patients' death. Circulating viruses are phenomenal for the disease outcome. This hypothesis proposes a therapeutic strategy utilizing receptor-integrated hematopoietic, erythroid and red blood cells. Here, HIV specific receptors trap circulating viruses that enter erythrocyte cytoplasm and form inactive integration complex. This model depicts easy, effective removal of circulating HIV without any adverse effect...
December 2018: Journal of Biological Research
Clovis S Palmer, Riya Palchaudhuri, Hassan Albargy, Mohamed Abdel-Mohsen, Suzanne M Crowe
An emerging paradigm in immunology suggests that metabolic reprogramming and immune cell activation and functions are intricately linked. Viral infections, such as HIV infection, as well as cancer force immune cells to undergo major metabolic challenges. Cells must divert energy resources in order to mount an effective immune response. However, the fact that immune cells adopt specific metabolic programs to provide host defense against intracellular pathogens and how this metabolic shift impacts immune cell functions and the natural course of diseases have only recently been appreciated...
2018: F1000Research
A Dakiw Piaceski, D Larouche, K Ghani, F Bisson, S Cortez Ghio, S Larochelle, M J Moulin, M Caruso, L Germain
The combination of gene therapy and tissue engineering is one of the most promising strategies for the treatment of recessive dystrophic epidermolysis bullosa (RDEB). RDEB is a rare genetic disease characterised by mutations in the COL7A1 gene, encoding type VII collagen (COLVII), which forms anchoring fibrils at the dermal-epidermal junction of the skin. This disease causes severe blistering and only palliative treatments are offered. In this study, the base of a strategy combining gene therapy and a tissue-engineered skin substitute (TES), which would be suitable for the permanent closure of skin wounds, was set-up...
February 14, 2018: European Cells & Materials
Ron Zhi-Hui Chiang, Samuel Ken-En Gan, Chinh Tran-To Su
HIV drug resistant mutations that render the current Highly Active Anti-Retroviral Therapy cocktail drugs ineffective are increasingly reported. To study the mechanisms of these mutations in conferring drug resistance, we computationally analyzed fourteen Reverse Transcriptase (RT) structures of HIV-1 on the following parameters: drug-binding pocket volume, allosteric effects caused by the mutations, and structural thermal stability. We constructed structural correlation-based networks of the mutant RT-drug complexes and the analyses support the use of Efavirenz as the first-line drug, given that cross-resistance is least likely to develop from Efavirenz-resistant mutations...
February 5, 2018: Bioscience Reports
Shi-Lung Lin, Shin-Ju E Chang, Shao-Yao Ying
Transgenic animal models are valuable tools for testing gene functions and drug mechanisms in vivo. They are also the best similitude for a human body for etiological and pathological research of diseases. All pharmaceutically developed medicines must be proven to be safe and effective in animals before approval by the Food and Drug Administration (FDA) to be used in clinical trials. To this end, the transgenic animal models of diseases serve as the front line of drug evaluation. However, there is currently no transgenic animal model for microRNA (miRNA)-related research...
2018: Methods in Molecular Biology
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