Trial reportPharmacology research & perspectives2020
Phase I evaluation of the safety, tolerability, and pharmacokinetics of GSK3640254, a next-generation HIV-1 maturation inhibitor.
Trial report in Pharmacology research & perspectives, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Double-Blind (Sponsor Unblinded), Randomized, Placebo-Controlled, Single and Repeated Dose Escalation Study to Investigate the Safety, Tolerability and Pharmacokinetics of GSK3640254 in Healthy Participants
A Single Centre, 2-period, Randomized, Open-label Phase 1 Study to Assess the Relative Bioavailability of a Mesylate Salt Capsule of GSK3640254 Compared to a Hydrochloride Salt Capsule in Healthy Participants
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Current ARTs, Virologic Failure, and Implications for AIDS Management: A Systematic Review.Viruses · 2023Pooled it
- Effects of the HIV-1 maturation inhibitor GSK3640254 on QT interval in healthy participants.Pharmacology research & perspectives · 2023Trial
- A phase I, first-in-human study investigating the safety, tolerability, and pharmacokinetics of the maturation inhibitor GSK3739937.Pharmacology research & perspectives · 2023Trial
- Phase IIa Proof-of-Concept Evaluation of the Antiviral Efficacy, Safety, Tolerability, and Pharmacokinetics of the Next-Generation Maturation Inhibitor GSK3640254.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Trial
- Relative Bioavailability and Food Effect of GSK3640254 Tablet and Capsule Formulations in Healthy Participants.Clinical pharmacology in drug development · 2022Trial
- Phase I evaluation of the safety, tolerability, and pharmacokinetics of GSK3640254, a next-generation HIV-1 maturation inhibitor.Pharmacology research & perspectives · 2020Trial
- Efficacy and safety of the HIV-1 maturation inhibitor GSK3640254 plus two NRTIs in adults naive to antiretroviral therapy (DOMINO): 24-week results from a randomised phase 2b study.EClinicalMedicine · 2025Article
- Efficacy and safety of the HIV-1 maturation inhibitor GSK3640254 plus dolutegravir as a two-drug regimen in adults naive to antiretroviral therapy (DYNAMIC): 24-week results from a randomised phase 2b study.EClinicalMedicine · 2025Article
- Invention of VH-937, a Potent HIV-1 Maturation Inhibitor with the Potential for Infrequent Oral Dosing in Humans.ACS medicinal chemistry letters · 2024Article
- Article
- Structure-function analyses reveal key molecular determinants of HIV-1 CRF01_AE resistance to the entry inhibitor temsavir.Nature communications · 2023Article
- Sub-stoichiometric Modulation of Viral Targets-Potent Antiviral Agents That Exploit Target Vulnerability.ACS medicinal chemistry letters · 2023Article
- Integrating In Vitro Biopharmaceutics into Physiologically Based Biopharmaceutic Model (PBBM) to Predict Food Effect of BCS IV Zwitterionic Drug (GSK3640254).Pharmaceutics · 2023Article
- Strategies to overcome HIV drug resistance-current and future perspectives.Frontiers in microbiology · 2023Review
- Lack of pharmacokinetic interaction between the HIV-1 maturation inhibitor GSK3640254 and combination oral contraceptives in healthy women.British journal of clinical pharmacology · 2022Article
- GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile.Antimicrobial agents and chemotherapy · 2022Article
- Phase I evaluation of pharmacokinetics and tolerability of the HIV-1 maturation inhibitor GSK3640254 and dolutegravir in healthy adults.British journal of clinical pharmacology · 2021Article
- A Phase I Evaluation of the Pharmacokinetics and Tolerability of the HIV-1 Maturation Inhibitor GSK3640254 and Tenofovir Alafenamide/Emtricitabine in Healthy Participants.Antimicrobial agents and chemotherapy · 2021Article
- A single G10T polymorphism in HIV-1 subtype C Gag-SP1 regulates sensitivity to maturation inhibitors.Retrovirology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite advances in HIV-1 management with antiretroviral therapy, drug resistance and toxicities with multidrug regimens can result in treatment failure. Hence, there is a continuing demand for antiretroviral agents (ARVs) with novel mechanisms of action. Maturation inhibitors inhibit HIV-1 replication via a unique mechanism of action and can be combined with other ARVs. Two phase I randomized clinical trials were conducted for a maturation inhibitor, GSK3640254, to determine safety, pharmacokinetics (NCT03231943), and relative bioavailability (NCT03575962) in healthy adults. The first trial was conducted in two parts. Part 1 was conducted in a two-cohort, interlocking, eight-period fashion in 20 participants with single ascending doses of GSK3640254 (1-700 mg) or placebo. In Part 2, 58 participants were randomized to receive GSK3640254 (n = 44) or placebo (n = 14). Four participants reported adverse events (AEs) leading to study discontinuation, with one adverse drug reaction (maculopapular rash). There was no relationship between frequency or severity of AEs and dose. Pharmacokinetic assessments showed that GSK3640254 was slowly absorbed, with time to maximum concentration (tmax) occurring between 3.5 and 4 hours and half-life of ~24 hours. In the relative bioavailability study of GSK3640254 mesylate salt vs bis-hydrochloride salt capsules in 14 healthy adults, the mesylate salt performed slightly better than the bis-hydrochloride formulation (12%-16% increase in area under the concentration-time curve and maximum concentration); tmax (5 hours) was similar between the formulations. Initial pharmacokinetic and safety data from these healthy-participant studies informed further development of GSK3640254 for once-daily dosing for the treatment of HIV-1 infection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.