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Summary: The purpose of this study is to summarize the current evidence on lenacapavir, a first-in-class HIV-1 capsid inhibitor, and its role as an emerging therapy for the treatment of HIV-1 infection. Recent findings indicate that lenacapavir, as a HIV-1 capsid inhibitor, may have activity against multidrug-resistant HIV-1 viral isolates. Initial results from clinical trials suggest that lenacapavir-containing regimens may be effective for patients with multidrug resistance and limited antiviral options.
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Emmanuel Ndashimye et al.
Summary: Combined HIV antiretroviral therapy (cART) has been effective in controlling HIV, but drug resistance is a significant concern, particularly in low-income countries. This review explores the factors contributing to higher rates of drug resistance in these countries, including the initial use of less tolerated cART regimens and issues with drug supply and monitoring. The study also compares the inhibition and resistance of different HIV-1 subtypes to approved drugs and provides insights for patient care and policymakers to reduce drug resistance.
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Ming J. Lee et al.
Summary: In recent years, advances have been made in understanding the persistence of latent HIV and developing more accurate assays for measuring the intact proviral reservoir. Broadly neutralising antibodies and techniques to enhance antibody responses have shown promising results. Other strategies such as therapeutic vaccination, latency reversal agents, and immunomodulatory agents have shown limited success, but newer interventions like engineered T cells may offer a potent strategy for achieving HIV cure.
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Nicolas Margot et al.
Summary: Through in vitro and clinical assays, this study found that mutations in HIV-1 capsid protein are associated with increased resistance to Lenacapavir, but also decreased replication capacity of the mutant viruses. In the clinical trial, all participants who received Lenacapavir treatment showed a robust virological response without any detected resistance mutations.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
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Hadas Dvory-Sobol et al.
Summary: This review summarizes the available data for lenacapavir, a novel agent that disrupts the functioning of HIV capsid protein in multiple steps of the viral life cycle. The findings indicate that lenacapavir demonstrates potent antiviral activity against HIV-1, with no preexisting resistance observed in individuals with HIV-1 regardless of treatment history. It can be administered orally or subcutaneously, and has shown high rates of virological suppression and good tolerability when used in combination with other antiretroviral agents. Ongoing studies are exploring the potential of long-acting dosing for lenacapavir in treating HIV-1 and as a standalone agent for preventing HIV-1.
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Summary: With older adults living longer with HIV, the incidence of HIV comorbidities is on the rise. A study conducted in South Africa found that older adults (50 years and older) with HIV were four times more likely to have comorbidities compared to younger adults. Being female and living in an urban area were factors associated with higher odds of HIV comorbidity. Comprehensive healthcare is necessary for older adults with HIV to address multiple conditions and maximize the benefits of HIV therapies.
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Summary: This study reviews the discovery, development, inventions, and patent literature of fexinidazole (FEX), which has been approved as the first all-oral therapy for Human African trypanosomiasis (HAT). The review highlights the potential for further inventions and innovations based on FEX for the treatment of other diseases.
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Summary: With the continuous development of drug therapy, the management of multidrug-resistant HIV-1 is no longer common. While protease inhibitors have saved lives, there is also resistance to nucleoside reverse-transcriptase inhibitors (NRTIs) among some patients. The subsequent availability of new drug classes has provided these patients with the option of monotherapy.
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Summary: Long-acting anti-HIV regimens have the potential to improve patients' quality of life by increasing dosing intervals. The combination therapy of lenacapavir with islatravir, rilpivirine, or cabotegravir shows additive inhibition in an HIV-1 reporter cell line. This study emphasizes the importance of effective drug combinations in long-acting regimens.
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Microbiology
Paloma Troyano-Hernaez et al.
Summary: The HIV-1 p24 protein plays a crucial role in the viral replication cycle and is important for vaccine design and antiretroviral drug development. This study analyzed the diversity of p24 among different HIV-1 variants and within its secondary structure. The results showed variations in conservation among different variants and secondary structure types, with overall high conservation. These findings provide valuable information for understanding the variability of p24 and developing effective strategies against HIV-1.
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Michelle Cespedes et al.
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Pharmacology & Pharmacy
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Marta Rosas et al.
Summary: The treatment of HIV infection is crucial for both individual health and the prevention of transmission. It should be initiated as early as possible, ideally on the same day of diagnosis or within the first week. Effective and convenient antiretroviral regimens incorporating second-generation integrase inhibitors are currently available.
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Summary: Monkeypox disease (MPX) is a global threat and Tecovirimat has been approved as the first treatment for MPX. Tecovirimat, initially developed as an anti-orthopoxvirus molecule, has shown efficacy in treating smallpox and MPX in animal studies. There is potential for off-label use of Tecovirimat and the development of new treatments for orthopoxvirus and other viral diseases.
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Stephanie M. Bester et al.
Summary: In this study, the researchers investigated the drug resistance of HIV-1 to Lenacapavir. They found that the Q67H and N74D mutations reduced the binding affinity of the inhibitor, and proposed a modification to increase its potency.
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Guochao Wei et al.
Summary: This study highlights the importance of prion-like low complexity domains in binding and increasing the avidity when interacting with viral capsid, through structural, biochemical, and virological assays.
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Somya Gupta et al.
Summary: This review discusses the goals of the HIV pandemic and the challenges it faces in terms of budgeting, resource allocation, and treatment coverage. Currently, many HIV-positive individuals are still not receiving treatment, and the target of diagnosing 95% of HIV-positive individuals, providing antiretroviral therapy to 95% of those diagnosed, and achieving viral suppression in 95% of those treated by 2030 has not yet been met.
CURRENT OPINION IN HIV AND AIDS
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Public, Environmental & Occupational Health
Mohammed Kanan Alshammari et al.
Summary: Selenium plays an important role in preventing/treating COVID-19 by reducing oxidative stress, inhibiting viral enzymes, and regulating inflammatory response. Clinical studies and patent literature suggest that selenium monotherapy or combination with other nutritional supplements/drugs could be practical for COVID-19 prevention/treatment. Selenium deficiency is correlated with COVID-19, indicating promising treatment outcomes with selenium supplementation. Thus, there is a significant need to develop novel selenium-based compositions and dosage forms to combat COVID-19 effectively.
JOURNAL OF INFECTION AND PUBLIC HEALTH
(2022)
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Medicine, General & Internal
Georgios K. Nikolopoulos et al.
Summary: This review summarizes the evolution of efforts to develop assays for the detection of recent HIV infection and to use these assays for the cross-sectional estimation of HIV incidence or for prevention purposes.
Review
Biochemistry & Molecular Biology
Mohd. Imran et al.
Summary: Tuberculosis (TB) is a global disease with long treatment duration and drug resistance issues. New drugs like SQ109, an inhibitor of MmpL3, are needed to shorten the treatment duration and control TB. SQ109 has shown activity against Mycobacterium tuberculosis and synergistic effects with other anti-TB drugs. The combination therapy of SQ109 with other drugs has been patented for its excellent anti-TB activity.
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Monika Walter
MMW Fortschritte der Medizin
(2022)
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Medicine, General & Internal
Sorana Segal-Maurer et al.
Summary: Patients with multidrug-resistant HIV-1 infection showed greater reduction in viral load when treated with lenacapavir compared to placebo.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Review
Chemistry, Medicinal
Mohd. Imran et al.
Summary: Protein kinase inhibitors are important therapeutic agents primarily used for treating cancer and inflammatory diseases. With time, more PKIs are expected to enter the generic drug market, potentially reducing the financial toxicity associated with existing PKIs. Despite the significant number of PKIs approved by the USFDA, there remains a large number of unexplored PKs.
Article
Microbiology
Nicolas Margot et al.
Summary: LEN is a potent inhibitor of HIV-1 capsid and has shown strong antiviral response in mutants with Gag cleavage site mutations and resistance to other drug classes. While LEN demonstrated wild-type susceptibility, reduced susceptibility was observed for control drugs.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
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Virology
Shentian Zhuang et al.
Summary: This paper reviews the interplay between the HIV-1 capsid and host factors during early stages of viral replication, highlighting the structure of the capsid, host factor interactions, and screening techniques. Understanding these interactions can inform HIV-1 pathogenesis and the development of capsid-centric antiretroviral therapeutics. The discovery of the capsid-targeting inhibitor GS-6207 represents a significant advancement in this field.
Review
Biology
Eric Rossi et al.
Summary: The capsid (CA) protein of HIV-1 plays crucial roles in shielding the reverse transcription complex, facilitating trafficking to the nucleus, and forming the capsid core during viral maturation. Understanding the functions of CA could lead to the development of potential therapeutic targets for HIV-1 inhibitors.
Review
Microbiology
Giancarlo Ceccarelli et al.
Summary: HIV-2 infection is prevalent in West Africa but also occurs in other parts of the world. It is less transmissible than HIV-1 and has resistance to certain antiretroviral drugs, leading to the risk of misdiagnosis and treatment failures. Clinicians need to consider the possibility of HIV-2 infection in clinical practice to optimize treatment outcomes.
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David Back et al.
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John O. Link et al.
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Frontiers of Medicine
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