GSK2838232 / GSK - LARVOL DELTA

Current status of the small molecule anti-HIV drugs in the pipeline or recently approved. (PubMed, Bioorg Med Chem) - "These compounds include analogues of nucleoside reverse transcriptase inhibitors (NRTIs) - islatravir and censavudine; non-nucleoside reverse transcriptase inhibitors (NNRTIs) - Rilpivirine, elsulfavirine and doravirine; integrase inhibitors namely cabotegravir and dolutegravir and chemokine coreceptors 5 and 2 (CC5/CCR2) antagonists for example cenicriviroc. Also, fostemsavir is being developed as an attachment inhibitor while lenacapavir, VH4004280 and VH4011499 are capsid inhibitors. Others are maturation inhibitors such as GSK-254, GSK3532795, GSK3739937, GSK2838232, and other compounds labelled as miscellaneous (do not belong to the classical groups of anti-HIV drugs or to the newer classes) such as obefazimod and BIT225. There is a considerable progress in the development of new anti-HIV drugs and the effort will continue since HIV infections has no cure or vaccine till now. Efforts are needed to reduce the toxicity of available drugs or discover new drugs with new..."

Journal • Review • Human Immunodeficiency Virus • Infectious Disease • CCR2

Parenteral platforms for tunable, long-acting administration of a highly hydrophobic antiretroviral drug. (PubMed, Sci Rep) - "GSK2838232 (GSK8232) is a second-generation maturation inhibitor (MI) developed for the treatment of HIV with excellent broad-spectrum virological profiles...Additionally, we were able to tune drug release rates through a combination of passive and active strategies, broadening applicability of these formulation approaches beyond GSK8232. Taken together, this report is an important first step to advance long-acting formulation development for critical HIV medicines that do not fit the traditional profile of suitable long-acting candidates."

Journal • Human Immunodeficiency Virus • Infectious Disease

Intrinsic resistance of HIV-2 and SIV to the maturation inhibitor GSK2838232. (PubMed, PLoS One) - "Collectively, our data indicate that the HIV-2 and SIV isolates tested in our study are intrinsically resistant to GSK232, and that the determinants of resistance map to CA/SP1. The molecular mechanism(s) responsible for the differential susceptibility of HIV-1 and HIV-2/SIV to GSK232 require further investigation."

Journal • Human Immunodeficiency Virus • Infectious Disease • IGFBP7

INTRINSIC RESISTANCE OF HIV-2 AND SIV TO THE MATURATION INHIBITOR GSK2838232 (CROI 2022) - "The mechanism(s) responsible for the differential susceptibility of HIV-1 and HIV-2/SIV to GSK232 require further investigation. Our data suggest that GSK232 is not a suitable candidate for antiretroviral therapy of HIV-2 infection."

Human Immunodeficiency Virus • Infectious Disease • IGFBP7

Are Myths and Preconceptions Preventing us from Applying Ionic Liquid Forms of Antiviral Medicines to the Current Health Crisis? (PubMed, Int J Mol Sci) - "In this perspective article, the myths and the most voiced concerns holding back implementation of API-ILs are examined, and two case studies of API-ILs antivirals (the amphoteric acyclovir and GSK2838232) are presented in detail, with a focus on drug property improvement. We advocate that the industry should consider the advantages of API-ILs which could be the genesis of disruptive innovation and believe that in order for the industry to grow and develop, the industry should be comfortable with a certain element of risk because progress often only comes from trying something different."

Journal • Infectious Disease • Novel Coronavirus Disease

A Phase 1 Study to Assess the Relative Bioavailability, Food Effect, and Safety of a Tablet Formulation of GSK2838232, a Novel HIV Maturation Inhibitor in Healthy Participants After Single and Repeated Doses. (PubMed, Clin Pharmacol Drug Dev) - "Steady-state concentrations were achieved by day 3 with a geometric mean steady-state Cτ on day 11 of 28 ng/mL. The tablet formulation was generally well tolerated as a single 200-mg dose with RTV under fed and fasted conditions and following administration of multiple daily doses (11 days) of 500 mg unboosted."

Clinical • Journal • P1 data • Gene Therapies • Infectious Disease

Local structural effects due to micronization and amorphization on an HIV treatment active pharmaceutical ingredient. (PubMed, Mol Pharm) - "Here, x-ray powder diffraction (XRPD), total scattering pair distribution function (TSPDF) analysis, and solid-state nuclear magnetic resonance spectroscopy (SSNMR) have been performed on samples of GSK2838232B, an investigational drug for the treatment of human immunodeficiency virus (HIV)...Microfluidic injection was shown to result in a different local structure due to dispersion with dichloromethane (DCM). Implications of combined TSPDF and SSNMR studies to characterize molecular compounds are also discussed, in particular, the possibility to obtain a thorough structural understanding of samples disordered using different processes."

Journal • Gene Therapies • Genetic Disorders • Human Immunodeficiency Virus • Infectious Disease

A Phase IIa Study Evaluating Safety, Pharmacokinetics, and Antiviral Activity of GSK2838232, a Novel, Second-generation Maturation Inhibitor, in Participants With Human Immunodeficiency Virus Type 1 Infection. (PubMed, Clin Infect Dis) - P2a; "GSK2838232 with cobicistat was well tolerated and exhibited efficacy as a short-term monotherapy in participants with HIV-1. This positive proof-of-concept study supports the continued development of GSK2838232 for the treatment of HIV as part of combination antiretroviral therapy."

Clinical • Journal • P2a data • PK/PD data

A PHASE IIA STUDY OF NOVEL MATURATION INHIBITOR GSK2838232 IN HIV PATIENTS (CROI 2019) - "GSK2838232 demonstrated short-term tolerability and antiviral activity, with the maximal response observed in the highest dose cohort. Preliminary evidence of clinical activity observed in HIV patients provides a positive proof of concept for further exploration of GSK2838232."

Clinical • P2a data

EMERGENCE OF GAG MUTATION, A364V, IDENTIFIED AS THE KEY IN VITRO RESISTANCE MUTATION (CROI 2019) - "Based on the infrequent presence of the A364V mutation, pre-existing resistance in an HIV-positive human patient population is expected to be low. As GSK2838232 progresses through clinical development, these in vitro resistance data will help decipher the genotypic and phenotypic observations from those clinical studies."