Islatravir for the treatment and prevention of infection with the human immunodeficiency virus type 1

Purpose of review To discuss the potential role of islatravir (ISL), a novel reverse transcriptase translocation inhibitor, in the treatment and prevention of human immunodeficiency virus type 1 (HIV-1) infection. Recent findings Islatravir (4′-ethynyl-2-fluoro-2′-deoxyadenosine, MK-8591) is a long-acting first-in-class nucleoside reverse transcriptase translocation inhibitor with the potential for versatile dosing routes and dosing intervals. It demonstrated robust antiviral activity when dosed once daily and once weekly in HIV-1-infected individuals and SIV-infected rhesus macaques. In clinical trials of ISL in combination with doravirine and lamivudine, daily oral administration resulted in high levels of virologic suppression in HIV-infected individuals. In preclinical studies, ISL dosed orally once-weekly as preexposure prophylaxis (PrEP), protected rhesus macaques against SHIV infection via the mucosal route in the low-dose rectal challenge model. Most recently, data in healthy HIV-1-uninfected individuals demonstrated the feasibility of formulating of ISL as an implant. In these studies, levels of intracellular ISL-triphosphate were consistent with the potential for a once-yearly implantable administration of ISL as PrEP. Summary Islatravir is a promising new agent for both the treatment and prevention of HIV-1 infection.
Source: Current Opinion in HIV and AIDS - Category: Infectious Diseases Tags: LONG ACTING ART FOR TREATMENT AND PREVENTION: Edited by Martin Markowitz Source Type: research

Related Links:

No abstract available
Source: AIDS - Category: Infectious Diseases Tags: Correspondence Source Type: research
Purpose of review Subcutaneous implants are a promising technology to enable long-acting parenteral delivery of antiretroviral drugs (ARV) because they may be able to provide protective drugs concentrations for a year or longer following a single implant. The present review covers the current status of preclinical and clinical development of antiretroviral implants. Recent findings Over the past three decades, subcutaneous implants have been widely used for long-acting hormonal contraception and the treatment of hormonally-driven malignancies. They are economical and scalable to manufacture, but require special proced...
Source: Current Opinion in HIV and AIDS - Category: Infectious Diseases Tags: LONG ACTING ART FOR TREATMENT AND PREVENTION: Edited by Martin Markowitz Source Type: research
Conclusion: HIV-mediated immunological disruption is greater in the duodenum than rectum and blood before and during ART. Small intestine damage may represent a unique environment for T-cell depletion, which might be attenuated by interaction with Gram-positive bacteria.
Source: AIDS - Category: Infectious Diseases Tags: BASIC SCIENCE Source Type: research
Publication date: Available online 20 November 2019Source: Neuroscience LettersAuthor(s): Sathiya Sekar, Changiz TaghibiglouAbstractGlyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been well documented in glycolytic pathway. Independent of this, it has various other functions including stimulator of programmed cell death. Reports suggest that glutamate receptor AMPA type-2 subunit (GluA2) forms protein complex with GAPDH and internalized during excitotoxicity. Further, nuclear accumulation of GluA2 and GAPDH have been studied in neurological disorders like epilepsy and multiple sclerosis, and disruption of this complex...
Source: Neuroscience Letters - Category: Neuroscience Source Type: research
AbstractCell surface translocation of the chaperone glucose ‐regulated protein 78 kDa (GRP78) is a key event that promotes cancer cell survival during endoplasmic reticulum stress. Here, we identify Gα‐Interacting Vesicle‐Associated Protein (GIV) — an enhancer of pro‐survival signaling during ER stress — as a binding partner of GRP78. We show th at GIV and GRP78 interact in an ER stress‐dependent manner through their respective carboxyl terminal domains and that GIV aids in the localization of GRP78 to the plasma membrane. Kaplan‐Meier analysis of disease‐free survival in cancer patients sho...
Source: FEBS Letters - Category: Biochemistry Authors: Tags: Research Letter Source Type: research
Consuming a high-fat diet (HFD) is a risk factor for obesity and diabetes; both of these diseases are also associated with systemic inflammation, similar to HIV infection. A HFD induces intestinal dysbiosis and impairs liver function and coagulation, with a potential negative impact on HIV/SIV pathogenesis. We administered a HFD rich in saturated fats and cholesterol to nonpathogenic (African green monkeys) and pathogenic (pigtailed macaques) SIV hosts. The HFD had a negative impact on SIV disease progression in both species. Thus, increased cell-associated SIV DNA and RNA occurred in the HFD-receiving nonhuman primates, i...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
In this study, we demonstrate for the first time the molecular events that contribute to osteogenic differentiation of PDLSCs. Dentin matrix protein 1 (DMP1) and its receptor, Glucose regulated protein-78 (GRP78), are localized in the progenitor cells of the PDL. Our overall goal is to demonstrate the formation of DMP1-GRP78 complex at the plasma membrane and subsequent protein trafficking and nuclear localization to promote osteogenic differentiation. To study the internalization and routing of the complex, we mimic an in vivo differentiation scenario by stimulating cells with DMP1 and culturing them in the presence of os...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
AbstractPurpose of ReviewPeople infected with HIV through injection drug use are more likely to experience progression to AIDS, death due to AIDS, and all-cause mortality even when controlling for access to care and antiretroviral therapy. While high-risk behavior and concurrent infections most certainly are contributors, chronic immune activation, downstream metabolic comorbidities may play an important role.Recent FindingsAltered intestinal integrity plays a major role in HIV-related immune activation and microbial translocation markers are heightened in active heroin users. Additionally, greater injection frequency driv...
Source: Current HIV/AIDS Reports - Category: Infectious Diseases Source Type: research
AbstractDespite antiretroviral therapy (ART), people living with HIV (PLWH) have higher rates of non-AIDS disorders, such as neurocognitive (NC) impairment (NCI) than the general population. (1-3)- β-d-Glucan (BDG) is a fungal cell wall component which serves as a biomarker for gut barrier integrity failure and microbial and fungal translocation. The primary objective of this study was to determine whether higher plasma and cerebrospinal fluid (CSF) levels of BDG and suPAR were associated with NCI in PLWH. Paired blood and CSF samples were collected cross-sectionally from 61 male adult PLWH on ART (95% virally suppres...
Source: Journal of NeuroVirology - Category: Neurology Source Type: research
Conclusion: The relative preservation of IL-17-producing γδ T cells in HIC and their negative association with immune activation raise the hypothesis that Tγδ17 cells – potentially through prevention of microbial translocation – may participate in the control of chronic systemic immune activation.
Source: AIDS - Category: Infectious Diseases Tags: BASIC SCIENCE Source Type: research
More News: Clinical Trials | HIV AIDS | Infectious Diseases | Study | Translocation | Virology