Evidence map›Paper›PMID 34343443›Full record

ArticleAntiviral chemistry & chemotherapy

V3-Loop genotypes do not predict maraviroc susceptibility of CCR5-tropic virus or clinical response through week 48 in HIV-1-infected, treatment-experienced persons receiving optimized background regimens.

M E Lewis, P Simpson, J Mori, B Jubb, J Sullivan, L McFadyen, E van der Ryst, C Craig, D L Robertson, M Westby

Open access · hybridAbstract read
In one paragraph

Article in Antiviral chemistry & chemotherapy. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.3field-weighted citation impact, top 48% 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

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

M E LewisPfizer Global Research and Development, Sandwich Labs, Sandwich, Kent, UK.
P SimpsonPfizer Global Research and Development, Sandwich Labs, Sandwich, Kent, UK.
J MoriPfizer Global Research and Development, Sandwich Labs, Sandwich, Kent, UK.
B JubbPfizer Global Research and Development, Sandwich Labs, Sandwich, Kent, UK.
J SullivanPfizer Global Research and Development, Sandwich Labs, Sandwich, Kent, UK.
L McFadyenPfizer Inc, Pharmacometrics, Sandwich, UK.
E van der RystPfizer Global Research and Development, Sandwich Labs, Sandwich, Kent, UK.ORCID https://orcid.org/0000-0002-9193-1825
C CraigPfizer Global Research and Development, Sandwich Labs, Sandwich, Kent, UK.ORCID https://orcid.org/0000-0003-3276-9925
D L RobertsonMRC-University of Glasgow Centre for Virus Research, Glasgow, UK.
M WestbyPfizer Global Research and Development, Sandwich Labs, Sandwich, Kent, UK.
Pfizer (United Kingdom) · GBAstraZeneca (United Kingdom) · GBMRC University of Glasgow Centre for Virus Research · GB

Funding

Medical Research Council G1001806
6 · The paper itself

Abstract

Viruses from 15 of 35 maraviroc-treated participants with virologic failure and CCR5-tropic (R5) virus in the MOTIVATE studies at Week 24 had reduced maraviroc susceptibility. On-treatment amino acid changes were observed in the viral envelope glycoprotein 120 third variable (V3)-loop stems and tips and differed between viruses. No amino acid change reliably predicted reduced susceptibility, indicating that resistance was genetic context-dependent. Through Week 24, poor adherence was associated with maraviroc-susceptible virologic failure, whereas reduced maraviroc susceptibility was associated with suboptimal background regimen activity, highlighting the importance of overall regimen activity and good adherence. Predictive values of pretreatment V3-loop sequences containing these Week 24 mutations or other variants present at >3% in pretreatment viruses of participants with virologic failure at Week 48 were retrospectively assessed. Week 48 clinical outcomes were evaluated for correlates with pretreatment V3-loop CCR5-tropic sequences from 704 participants (366 responders; 338 virologic failures [83 with R5 virus with maraviroc susceptibility assessment]). Seventy-five amino acid variants with >3% prevalence were identified among 23 V3-loop residues. Previously identified variants associated with resistance in individual isolates were represented, but none were associated reliably with virologic failure alone or in combination. Univariate analysis showed virologic-failure associations with variants 4L, 11R, and 19S (

Indexed as

HIV-1HIV InfectionsGenotypeHumansMaravirocReceptors, CCR5Retrospective StudiesViral TropismCCR5 protein, humanMaravirocReceptors, CCR5HIV entrymaraviroc susceptibilityV3-loop genotype

Identifiers

PMID34343443
PMCPMC8369958
OpenAlexW3192112847

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

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.