Evidence map›Paper›PMID 31622432›Full record

Trial reportPloS one2019

Resistance profile of the HIV-1 maturation inhibitor GSK3532795 in vitro and in a clinical study.

Ira Dicker, Sharon Zhang, Neelanjana Ray, Brett R Beno, Alicia Regueiro-Ren, Samit Joshi, Mark Cockett, Mark Krystal, Max Lataillade

Erratum issuedOpen access · goldAbstract readClinical Trial, Phase II
In one paragraph

Trial report in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.5field-weighted citation impact, top 19% of its field
1 · What the graph read from 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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 19 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Ira DickerDepartment of HIV Discovery, ViiV Healthcare, Branford, Connecticut, United States of America.
Sharon ZhangDepartment of HIV Discovery, ViiV Healthcare, Branford, Connecticut, United States of America.
Neelanjana RayDepartment of Early Development, Bristol-Myers Squibb Research and Development, Princeton, New Jersey, United States of America.
Brett R BenoDepartment of Molecular Discovery Technologies, Bristol-Myers Squibb Research and Development, Wallingford, Connecticut, United States of America.
Alicia Regueiro-RenDepartment of Chemistry Bristol-Myers Squibb Research and Development, Wallingford Connecticut, United States of America.ORCID 0000-0003-2991-719X
Samit JoshiDepartment of Early Development, ViiV Healthcare, Branford, Connecticut, United States of America.
Mark CockettDepartment of HIV Discovery, ViiV Healthcare, Branford, Connecticut, United States of America.
Mark KrystalDepartment of HIV Discovery, ViiV Healthcare, Branford, Connecticut, United States of America.ORCID 0000-0001-8905-2584
Max LatailladeDepartment of Early Development, ViiV Healthcare, Branford, Connecticut, United States of America.
Bristol-Myers Squibb (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

GSK3532795 (formerly BMS955176) is a second-generation maturation inhibitor (MI) that progressed through a Phase 2b study for treatment of HIV-1 infection. Resistance development to GSK3532795 was evaluated through in vitro methods and was correlated with information obtained in a Phase 2a proof-of-concept study in HIV-1 infected participants. Both low and high concentrations of GSK3532795 were used for selections in vitro, and reduced susceptibility to GSK3532795 mapped specifically to amino acids near the capsid/ spacer peptide 1 (SP1) junction, the cleavage of which is blocked by MIs. Two key substitutions, A364V or V362I, were selected, the latter requiring secondary substitutions to reduce susceptibility to GSK3532795. Three main types of secondary substitutions were observed, none of which reduced GSK3532795 susceptibility in isolation. The first type was in the capsid C-terminal domain and downstream SP1 region (including (Gag numbering) R286K, A326T, T332S/N, I333V and V370A/M). The second, was an R41G substitution in viral protease that occurred with V362I. The third was seen in the capsid N-terminal domain, within the cyclophilin A binding domain (V218A/M, H219Q and G221E). H219Q increased viral replication capacity and reduced susceptibility of poorly growing viruses. In the Phase 2a study, a subset of these substitutions was also observed at baseline and some were selected following GSK35323795 treatment in HIV-1-infected participants.

Indexed as

Anti-HIV AgentsCapsid ProteinsDrug Resistance, Viralgag Gene Products, Human Immunodeficiency VirusGenotypeHIV-1HIV InfectionsHIV ProteaseHumansMutationVirus ReplicationAnti-HIV AgentsCapsid Proteinsgag Gene Products, Human Immunodeficiency VirusHIV Protease

Identifiers

PMID31622432
PMCPMC6797179
OpenAlexW2981247270

What OpenQuestion holds

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Registered trials

None linked

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.