Children’s Adherence to Antiretroviral Therapy and Associated Factors: Multi-center Cross-sectional Study

Background- Sub- optimal adherence to antiretroviral therapy will lead drug resistance, treatment failure, clinical deterioration, death and failure to thrive in children. Studies conducted among children below 15 years old were limited in Ethiopia in general and in study area in particular. Therefore, this study was aimed to assess status of children’s adherence to ART and associated factors in study area. Methods- We conduct a facility-based cross-sectional study by including total of 282 children <15 years, who received Anti retro viral therapy for at least one month. All children/caregivers who were attending ART clinic during data collection period were consecutively recruited to the study. Both bivariate and multivariate logistic regression were performed. Result- Out of 282 caregivers included with their children, 226(80.2%) were females (mean age= 38.6 and SD = 12.35) and out of the total children, half (50%) were female and 246(87.2%) were between the ages 5–14 years (mean age= 8.5 and SD = 2.64). Two hundred forty six (87.2%) children had adherence status of ≥95% in the month prior to interview. Children whose caregivers were residing in urban were 3.3 (95% CI: 1.17, 9.63) times more adherent to ART than those whose caregivers were residing in rural. Children whose caregivers were biological parent were 2.37(95% CI: 1.59, 3.3) times more adherent than those whose caregivers were non biological parent. Also children of caregivers who were knowledgeable about ART treatment, were 4.5(95% CI: 1.79, 9.8) times more adherent to ART than their counter partsConclusion and recommendation- Adherence status of children in our study area was comparable. Being biological caregivers, residing in urban and knowledgeable about ART treatment were facilitate adherence to ART. Ongoing education about treatment and further study with multiple adherence assessment method were recommended.

Glioblastoma: a molecular genetic portrait and modern therapeutic strategies for drug treatment

Glioblastoma multiforme is the most common and malignant primary tumor of the central nervous system. Despite the existing modern complex therapy and advances in the study of molecular genetic changes in this tumor, the prognosis for patients with glioblastoma is one of the most unfavorable in oncology. This overview reviews existing therapeutic agents and clinical studies of potential drugs for the treatment of patients with glioblastoma multiforme.Next-generation sequencing has become firmly established in the clinical practice of oncologists and allows detecting gene mutations in tumor cells, some of which can serve as targets for therapy. Glioblastoma is characterized by a large number of potentially targeted molecular genetic disorders. As in the case of other solid tumors, targeted and immunotherapy for glioblastomas is being actively studied, including the combination of drugs with physical methods of exposure. To date, new treatment methods of glioblastoma, including antiangiogenic therapy, immunotherapy, oncolytic viral therapy and gene therapy still have uncertain or very modest clinical results. There are many reasons for the lack of progress in the treatment of glioblastoma – from the banal inability of most molecules to overcome the blood-brain barrier to the wide genetic heterogeneity of these tumors. The most promising direction of studies is immunotherapy. But at this stage, we cannot say that there is an effective monotherapy for glioblastoma. The combination treatment with radiation therapy and chemotherapy increases the mutational load, the expression of stress and other factors, therefore, the researchers pin great hopes on the combined methods of treatment.

An Agent-Based Model of Combination Oncolytic Viral Therapy and Anti-PD-1 Immunotherapy Reveals the Importance of Spatial Location When Treating Glioblastoma

Oncolytic viral therapies and immunotherapies are of growing clinical interest due to their selectivity for tumor cells over healthy cells and their immunostimulatory properties. These treatment modalities provide promising alternatives to the standard of care, particularly for cancers with poor prognoses, such as the lethal brain tumor glioblastoma (GBM). However, uncertainty remains regarding optimal dosing strategies, including how the spatial location of viral doses impacts therapeutic efficacy and tumor landscape characteristics that are most conducive to producing an effective immune response. We develop a three-dimensional agent-based model (ABM) of GBM undergoing treatment with a combination of an oncolytic Herpes Simplex Virus and an anti-PD-1 immunotherapy. We use a mechanistic approach to model the interactions between distinct populations of immune cells, incorporating both innate and adaptive immune responses to oncolytic viral therapy and including a mechanism of adaptive immune suppression via the PD-1/PD-L1 checkpoint pathway. We utilize the spatially explicit nature of the ABM to determine optimal viral dosing in both the temporal and spatial contexts. After proposing an adaptive viral dosing strategy that chooses to dose sites at the location of highest tumor cell density, we find that, in most cases, this adaptive strategy produces a more effective treatment outcome than repeatedly dosing in the center of the tumor.

Assessing the Clinical Improvement in Patients with COVID-19 using Lopinavir-Ritonavir: A Systematic Review

Aims: Globally the focus is towards finding an effective treatment for COVID-19 patients in order to suppress the spread of this pandemic disease. An antiviral combination of lopinavir-ritonavir is considered to be effective in treating COVID-19 patients. Therefore, the present study aims to assess the clinical improvements of lopinavir-ritonavir in COVID-19 patients. Study Design: a systematic review study was conducted and articles published since December 2019 were included. The statistical analysis of quantitative data was performed using Review Manager (RevMan) to generate forest plots. Results: The study showed that there was no significant difference in COVID-19 patients treated with lopinavir-ritonavir or in combination with anti-viral therapy or other conventional methods. Conclusion: the use of lopinavir-ritonavir resulted in greater adverse consequences among COVID-19 patients. It further recommends conducting meta-analysis studies with a greater number of studies to highlight the clinical improvement associated with the use of Lopinavir-ritonavir.

Thrombosis in COVID-19 infection: Role of platelet activation-mediated immunity

Background Thrombosis plays an important role in the Coronavrus Disease 2019 (COVID-19) infection-related complications such as acute respiratory distress syndrome and myocardial infarction. Multiple factors such as oxygen demand injuries, endothelial cells injury related to infection, and plaque formation. Main body Platelets obtained from the patients may have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, showing that the increased activation potential recommends platelet can be hyper-activated in severely ill SARS-CoV-2 cases. Platelets contain multiple receptors that interact with specific ligands. Pathogen’s receptors such as Toll-like receptors (TLRs), NOD-like receptor, C-type lectin receptor family, glycoprotein (GP) such as GPαIIbβ3 and GPIbα which allow pathogens to interact with platelets. Platelet TLRs and NOD2 are involved in platelet activation and thrombosis. Accordingly, TLRs are critical receptors that could recognize various endogenous damage-associated molecular patterns and exogenous pathogen-associated molecular patterns (PAMPs). TLRs are considered as important components in the activation of innate immunity response against pathogenic and non-pathogenic components like damaged tissues. TLRs-1,-2,-4,-6,-7 expression on or within platelets has been reported previously. Various PAMPs were indicated to be capable of binding to platelet-TLRs and inducing both the activation and promotion of downstream proinflammatory signaling cascade. Conclusion It is possible that the increased TLRs expression and TLR-mediated platelets activation during COVID-19 may enhance vascular and coronary thrombosis. It may be hypothesized using TLRs antagonist and monoclonal antibody against P-selectin, as the marker of leukocyte recruitment and platelet activation, besides viral therapy provide therapeutic advances in fighting against the thrombosis related complications in COVID-19.

Strategies to Optimise Oncolytic Viral Therapies: The Role of Natural Killer Cells

Oncolytic viruses (OVs) are an emerging class of anti-cancer agents that replicate selectively within malignant cells and generate potent immune responses. Their potential efficacy has been shown in clinical trials, with talimogene laherparepvec (T-VEC or IMLYGIC®) now approved both in the United States and Europe. In healthy individuals, NK cells provide effective surveillance against cancer and viral infections. In oncolytic viral therapy, NK cells may render OV ineffective by rapid elimination of the propagating virus but could also improve therapeutic efficacy by preferential killing of OV-infected malignant cells. Existing evidence suggests that the overall effect of NK cells against OV is context dependent. In the past decade, the understanding of cancer and OV biology has improved significantly, which helped refine this class of treatments in early-phase clinical trials. In this review, we summarised different strategies that have been evaluated to modulate NK activities for improving OV therapeutic benefits. Further development of OVs will require a systematic approach to overcome the challenges of the production and delivery of complex gene and cell-based therapies in clinical settings.

Effects of Pegylated Interferon Alpha and Ribavirin (pegIFN-α/RBV) Therapeutic Approach on Regulatory T Cells in HCV-Monoinfected and HCV/HIV-Coinfected Patients

Approximately 25% of HIV-infected patients are co-infected with HCV. Notably, the burden of HCV infection (e.g., viral persistence, viral load, or HCV-related liver symptoms) is more pronounced in the presence of HIV co-infection. However, to date, the underlying immune mechanisms accounting for accelerated disease progression in HIV/HCV-coinfected individuals have not been described in sufficient detail. We hypothesized that regulatory T cells (Treg) bearing potent immunosuppressive capacities could not only play a substantial role in the pathogenesis of HCV/HIV coinfection but also modulate the response to the standard anti-viral therapy. Materials and Methods: To this end, we studied alterations in frequencies of Treg cells in correlation with other Treg-related and virus-related parameters in both HCV and HCV/HIV-infected patients subjected to standard pegIFN-α/RBV therapy. Results: Notably, we found that pegIFN-α/RBV therapy significantly increased levels of Treg cells in HCV-infected but not in HIV/HCV-coinfected individuals. Furthermore, HIV/HCV-coinfection was demonstrated to inhibit expansion of regulatory T cells during anti-viral treatment; thus, it might probably be responsible for viral persistence and HCV-related liver damage. Conclusions: Therapy with pegIFN-α/RBV demonstrated a significant effect on regulatory T cells in the course of HIV and/or HCV infection indicating a crucial role in the anti-viral immune response.