The current state of an HIV cure: innovative approaches and limitations.
Ontology highlight
ABSTRACT:
SUBMITTER:
PROVIDER: S-EPMC6491905 | biostudies-literature | 2019 Apr
REPOSITORIES: biostudies-literature
Publications
The current state of an HIV cure: innovative approaches and limitations.
EBioMedicine 20190401
Similar Datasets
Project description:Purpose of reviewA serious effort has begun to develop therapies that may be capable of eradicating established HIV infection in man. Because of the biological complexity of HIV infection that persists despite potent antiretroviral therapy, it is widely believed that if such therapies can be developed they will involve complex, multimodality approaches. We highlight some of the recent studies in this effort.Recent findingsAn inhibitor of histone deacetylase has been demonstrated to disrupt latency in man, and new histone deacetylase inhibitors have been identified. Other potential targets, such as histone methyltransferase, protein kinase C, and BRD4, have been recently studied. Model systems, both in primary cells and in animal models, are beginning to be validated. In the clinic, immune-based therapies to aid in the clearance of persistent infection are also being tested.SummaryIt is too early to know what combination eradication therapies for HIV infection will look like in the future, but candidate therapies and model systems to perform preclinical validation are beginning to take shape.
| S-EPMC3966301 | biostudies-literature
Project description:Photodynamic therapy (PDT) mostly relies on the generation of singlet oxygen, via the excitation of a photosensitizer, so that target tumor cells can be destroyed. PDT can be applied in the settings of several malignant diseases. In fact, the earliest preclinical applications date back to 1900's. Dougherty reported the treatment of skin tumors by PDT in 1978. Several further studies around 1980 demonstrated the effectiveness of PDT. Thus, the technique has attracted the attention of numerous researchers since then. Hematoporphyrin derivative received the FDA approval as a clinical application of PDT in 1995. We have indeed witnessed a considerable progress in the field over the last century. Given the fact that PDT has a favorable adverse event profile and can enhance anti-tumor immune responses as well as demonstrating minimally invasive characteristics, it is disappointing that PDT is not broadly utilized in the clinical setting for the treatment of malignant and/or non-malignant diseases. Several issues still hinder the development of PDT, such as those related with light, tissue oxygenation and inherent properties of the photosensitizers. Various photosensitizers have been designed/synthesized in order to overcome the limitations. In this Review, we provide a general overview of the mechanisms of action in terms of PDT in cancer, including the effects on immune system and vasculature as well as mechanisms related with tumor cell destruction. We will also briefly mention the application of PDT for non-malignant diseases. The current limitations of PDT utilization in cancer will be reviewed, since identifying problems associated with design/synthesis of photosensitizers as well as application of light and tissue oxygenation might pave the way for more effective PDT approaches. Furthermore, novel promising approaches to improve outcome in PDT such as selectivity, bioengineering, subcellular/organelle targeting, etc. will also be discussed in detail, since the potential of pioneering and exceptional approaches that aim to overcome the limitations and reveal the full potential of PDT in terms of clinical translation are undoubtedly exciting. A better understanding of novel concepts in the field (e.g. enhanced, two-stage, fractional PDT) will most likely prove to be very useful for pursuing and improving effective PDT strategies.
| S-EPMC8223074 | biostudies-literature
Project description:Immunotherapy in the context of treated HIV-1 infection aims to improve immune responses to achieve better control of the virus. To date, multifaceted immunotherapeutic approaches have been shown to reduce immune activation and increase CD4 T-lymphocyte counts, further to the effects of antiretroviral therapy alone, in addition to improving HIV-1-specific T-cell responses. While sterilizing cure of HIV-1 would involve elimination of all replication-competent virus, a functional cure in which the host has long-lasting control of viral replication may be more feasible. In this commentary, we discuss novel strategies aimed at targeting the latent viral reservoir with cure of HIV-1 infection being the ultimate goal, an achievement that would have considerable impact on worldwide HIV-1 infection.
| S-EPMC4635699 | biostudies-literature
Project description:In spite of the advances in antiretroviral therapy to treat HIV infection, the presence of a latent reservoir of HIV-infected cells represents the largest barrier towards finding a cure. Among the different strategies being pursued to eliminate or reduce this latent reservoir, the γc-cytokine IL-15 or its superagonist N-803 are currently under clinical investigation, either alone or with other interventions. They have been shown to reactivate latent HIV and enhance immune effector function, both of which are potentially required for effective reduction of latent reservoirs. In here, we present a comprehensive literature review of the different in vitro, ex vivo, and in vivo studies conducted to date that are aimed at targeting HIV reservoirs using IL-15 and N-803.
| S-EPMC10537516 | biostudies-literature
Project description:Therapeutic approaches towards a functional cure or eradication of HIV have gained renewed momentum upon encouraging data emerging from studies in SIV monkey models and recent results from human clinical studies. However, a multitude of questions remain to be addressed, including how to deal with the latent viral reservoir, how to boost the host immune response to the virus and what the hurdles are to reach relevant viral compartments in the body. Advances have been made especially with regard to identifying agents that can reactivate the latent virus in vivo and boost the cellular and humoral immunity, but it remains largely unclear whether any of these strategies can awaken a sufficiently large fraction of the viral reservoir and whether the boosted immunity can prevent rapid viral replication once antiretroviral treatments are stopped.
| S-EPMC7238401 | biostudies-literature
Project description:Purpose of reviewCombination antiretroviral therapy (ART) has enabled tremendous progress in suppressing HIV replication in infected patients. However, ART alone cannot eradicate HIV and its latent, persisting reservoirs. Novel approaches are needed to eradicate the virus or achieve functional cure in the absence of ART.Recent findingsAdoptive T-cell therapies were initially tested in HIV-infected individuals with limited efficiency. Benefiting from new and improved methodologies, an increasing array of CAR T-cell therapies has been successfully developed in the cancer immunotherapy field, demonstrating promising new avenues that could be applied to HIV. Numerous studies have characterized various HIV-specific CAR constructs, types of cytolytic effector cells, and CAR-expressing cells' trafficking to the reservoir compartments, warranting further in-vivo efforts. Notably, the ability of CAR cells to persist and function in low-antigen environments in vivo, that is, in ART-suppressed patients, remains unclear.SummaryDespite promising results in preclinical studies, only a handful of clinical trials have been initiated worldwide. Several obstacles remain prior to successful application of HIV-specific CAR T-cell therapies in patients. In this review, we survey the current state of the field, and address paths towards realizing the goal of an efficacious HIV CAR T-cell product.
| S-EPMC6993924 | biostudies-literature
Project description:Every year, cancer is responsible for millions of deaths worldwide and, even though much progress has been achieved in medicine, there are still many issues that must be addressed in order to improve cancer therapy. For this reason, oncological research is putting a lot of effort towards finding new and efficient therapies which can alleviate critical side effects caused by conventional treatments. Different technologies are currently under evaluation in clinical trials or have been already introduced into clinical practice. While nanomedicine is contributing to the development of biocompatible materials both for diagnostic and therapeutic purposes, bioengineering of extracellular vesicles and cells derived from patients has allowed designing ad hoc systems and univocal targeting strategies. In this review, we will provide an in-depth analysis of the most innovative advances in basic and applied cancer research.
| S-EPMC6753017 | biostudies-literature
Project description:ObjectiveTo quantify compliance with guideline recommendations for secondary prevention in peripheral artery disease (PAD) using natural language processing (NLP) tools deployed to an electronic health record (EHR) and investigate provider opinions regarding clinical decision support (CDS) to promote improved implementation of these strategies.Patients and methodsNatural language processing was used for automated identification of moderate to severe PAD cases from narrative clinical notes of an EHR of patients seen in consultation from May 13, 2015, to July 27, 2015. Guideline-recommended strategies assessed within 6 months of PAD diagnosis included therapy with statins, antiplatelet agents, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and smoking abstention. Subsequently, a provider survey was used to assess provider knowledge regarding PAD clinical practice guidelines, comfort in recommending secondary prevention strategies, and potential role for CDS.ResultsAmong 73 moderate to severe PAD cases identified by NLP, only 12 (16%) were on 4 guideline-recommended strategies. A total of 207 of 760 (27%) providers responded to the survey; of these 141 (68%) were generalists and 66 (32%) were specialists. Although 183 providers (88%) managed patients with PAD, 51 (25%) indicated they were uncomfortable doing so; 138 providers (67%) favored the development of a CDS system tailored for their practice and 146 (71%) agreed that an automated EHR-derived mortality risk score calculator for patients with PAD would be helpful.ConclusionNatural language processing tools can identify cases from EHRs to support quality metric studies. Findings of this pilot study demonstrate gaps in application of guideline-recommended strategies for secondary risk prevention for patients with moderate to severe PAD. Providers strongly support the development of CDS systems tailored to assist them in providing evidence-based care to patients with PAD at the point of care.
| S-EPMC6051413 | biostudies-literature
Project description:Depression is a highly debilitating disorder that has been estimated to affect up to 21% of the world population. Despite the advances in the treatment of depression with selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), there continue to be many unmet clinical needs with respect to both efficacy and side effects. These needs range from efficacy in treatment resistant patients, to improved onset, to reductions in side effects such as emesis or sexual dysfunction. To address these needs, there are numerous combination therapies and novel targets that have been identified that may demonstrate improvements in one or more areas. There is tremendous diversity in the types of targets and approaches being taken. At one end of a spectrum is combination therapies that maintain the benefits associated with SSRIs but attempt to either improve efficacy or reduce side effects by adding additional mechanisms (5-HT1A, 5-HT1B, 5-HT1D, 5-HT2C, alpha-2A). At the other end of the spectrum are more novel targets, such as neurotrophins (BDNF, IGF), based on recent findings that antidepressants induce neurogenesis. In between, there are many approaches that range from directly targeting serotonin receptors (5-HT2C, 5-HT6) to targeting the multiplicity of potential mechanisms associated with excitatory (glutamate, NMDA, mGluR2, mGluR5) or inhibitory amino acid systems (GABA) or peptidergic systems (neurokinin 1, corticotropin-releasing factor 1, melanin-concentrating hormone 1, V1b). The present review addresses the most exciting approaches and reviews the localization, neurochemical and behavioral data that provide the supporting rationale for each of these targets or target combinations.
| S-EPMC1201318 | biostudies-other
Project description:Mucopolysaccharidoses III (MPS III, Sanfilippo syndrome) is a subtype of the Mucopolysaccharidoses (MPS), a group of inherited lysosomal disorders caused by a deficiency of lysosomal enzymes responsible for catabolizing glycosaminoglycans (GAGs). Although MPS III is rare, MPS diseases as a group are relatively frequent with an overall incidence of approximately 1 in 20,000 - 25,000 births. MPS III are paediatric diseases, which cause learning difficulties, behavioural disorders and dementia, as well as skeletal deformities and ultimately result in premature death. There are currently no approved treatments for MPS III, but a number of therapeutic approaches are under development. In the past 30 years, research using cellular and animal models have led to clinical trials involving enzyme replacement therapy (ERT), substrate reduction therapy (SRT) and gene therapy, while stem cells approaches remain at the pre-clinical stage. Although safety and clinical efficacy in animal models have shown promise, the results of clinical trials have proved costly and shown limited therapeutic effects. In this review, we describe the most recent results from clinical trials. While ERT and gene therapy are the most developed therapies for MPS III, we highlight the work that needs to be done to bring us closer to a real treatment for these devastating diseases.
| S-EPMC7391468 | biostudies-literature