Trial reportClinical infectious diseases : an official publication of the Infectious Diseases Society of America2022
Phase IIa Proof-of-Concept Evaluation of the Antiviral Efficacy, Safety, Tolerability, and Pharmacokinetics of the Next-Generation Maturation Inhibitor GSK3640254.
Trial report in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2022. 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 12 papers, 1 of them a synthesis that pooled it.
What it found
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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 Randomized, Double-Blind (Sponsor-unblinded), Placebo-Controlled, Adaptive Trial to Investigate the Antiviral Effect, Safety, Tolerability and Pharmacokinetics of GSK3640254 in HIV-1 Infected Treatment-Naïve Adults
A Phase IIb, Randomized, Partially Blind, Active Controlled, Dose-range Finding Study of GSK3640254 Compared to a Reference Arm of Dolutegravir, Each in Combination With Nucleoside Reverse Transcriptase Inhibitors, in HIV-1 Infected Antiretroviral Treatment-naive Adults
Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 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
- Mechanisms of HIV-1 assembly, release and maturation.Nature reviews. Microbiology · 2026Review
- 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
- HIV Therapy: The Latest Developments in Antiviral Drugs-A Scoping Review.Biomedicines · 2025Review
- Invention of VH-937, a Potent HIV-1 Maturation Inhibitor with the Potential for Infrequent Oral Dosing in Humans.ACS medicinal chemistry letters · 2024Article
- 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
- Article
- GSK3640254 Is a Novel HIV-1 Maturation Inhibitor with an Optimized Virology Profile.Antimicrobial agents and chemotherapy · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 7 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGSK3640254 (GSK'254) is a next-generation human immunodeficiency virus type 1 (HIV-1) maturation inhibitor with pharmacokinetics (PK) supporting once-daily therapy.
methodsThis phase IIa double-blind (sponsor-unblinded), randomized, placebo-controlled, adaptive study evaluated antiviral effect, safety, tolerability, and PK of once-daily GSK'254 monotherapy administered with food (moderate-fat meal) in HIV-1-positive, treatment-naive adults. In part 1, participants received GSK'254 10 or 200 mg for 10 days. In part 2, participants received GSK'254 40, 80, or 140 mg for 7 days, modified from 10 days by a protocol amendment to decrease potential for resistance-associated mutations (RAMs). The primary endpoint was maximum change from baseline in HIV-1 RNA.
resultsMaximum changes in HIV-1 RNA of -0.4, -1.2, -1.0, -1.5, and -2.0 log10 occurred with GSK'254 10, 40, 80, 140, and 200 mg, respectively. Regardless of dosing duration, doses ≥40 mg resulted in ≥1-log10 declines in HIV-1 RNA. Plasma PK was generally dose proportional to 140 mg but non-proportional between 140 and 200 mg. Four participants in the 200-mg group developed RAMs on day 11 in part 1, 1 with phenotypic resistance. No RAMs occurred in part 2. Adverse events (AEs) were reported by 22 (65%) participants; headache was the most common (n = 4). Two non-drug-related serious AEs occurred. All AEs were of mild-to-moderate intensity, except for 2 grade 3 non-drug-related AEs in 1 participant.
conclusionsThis monotherapy study established a dose-antiviral response relationship for GSK'254. No safety or tolerability concerns were noted. These results supported dose selection for the ongoing phase IIb study (ClinicalTrials.gov: NCT04493216). CLINICAL TRIALS REGISTRATION: NCT03784079.
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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.