Evidence map›Paper›PMID 37515104›Full record

ArticleViruses2023

Added Value of Next Generation Sequencing in Characterizing the Evolution of HIV-1 Drug Resistance in Kenyan Youth.

Vlad Novitsky, Winstone Nyandiko, Rachel Vreeman, Allison K DeLong, Mark Howison, Akarsh Manne, Josephine Aluoch, Ashley Chory, Festus Sang, Celestine Ashimosi and 4 more

Open access · goldAbstract read
In one paragraph

Article in Viruses, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
1.4field-weighted citation impact, top 20% 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

7 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Review
  6. Molecular Footprints ofAdvances in virology · 2024
    Article
  7. 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

14 authors at 5 institutions in 2 countries.

Vlad NovitskyAlpert Medical School, Brown University, Providence, RI 02912, USA.
Winstone NyandikoAcademic Model Providing Access to Healthcare (AMPATH), Eldoret 30100, Kenya.
Rachel VreemanAcademic Model Providing Access to Healthcare (AMPATH), Eldoret 30100, Kenya.
Allison K DeLongSchool of Public Health, Brown University, Providence, RI 02912, USA.
Mark HowisonResearch Improving People's Lives, Providence, RI 02903, USA.ORCID 0000-0002-0764-4090
Akarsh ManneAlpert Medical School, Brown University, Providence, RI 02912, USA.
Josephine AluochAcademic Model Providing Access to Healthcare (AMPATH), Eldoret 30100, Kenya.
Ashley ChoryDepartment of Global Health and Health System Design, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0002-3551-5341
Festus SangAcademic Model Providing Access to Healthcare (AMPATH), Eldoret 30100, Kenya.ORCID 0000-0003-0284-9131
Celestine AshimosiAcademic Model Providing Access to Healthcare (AMPATH), Eldoret 30100, Kenya.
Eslyne JepkemboiAcademic Model Providing Access to Healthcare (AMPATH), Eldoret 30100, Kenya.
Millicent OridoAcademic Model Providing Access to Healthcare (AMPATH), Eldoret 30100, Kenya.
Joseph W HoganAcademic Model Providing Access to Healthcare (AMPATH), Eldoret 30100, Kenya.
Rami KantorAlpert Medical School, Brown University, Providence, RI 02912, USA.ORCID 0000-0003-3659-1108
AMPATH · KEBrown University · USMount Sinai Health System · USMoi University · KEProvidence College · US

Funding

Translational ScienceP30AI042853 · NIAID · MIRIAM HOSPITAL · PI CURT G BECKWITH, DEBBIE M. CHENG · 1998 to 2026
$51.7M
HIV Treatment Failure and Drug Resistance in Western Kenyan ChildrenR01AI120792 · NIAID · INDIANA UNIVERSITY INDIANAPOLIS · PI KANTOR, RAMI, VREEMAN, RACHEL CHRISTINE · 2016 to 2019
$2.9M
HIV Drug Resistance, Monitoring and TransmissionK24AI134359 · NIAID · MIRIAM HOSPITAL · PI Rami Kantor · 2018 to 2026
$1.3M
NIAID NIH HHS AI042853NIAID NIH HHS AI120792NIAID NIH HHS AI134359
6 · The paper itself

Abstract

Drug resistance remains a global challenge in children and adolescents living with HIV (CALWH). Characterizing resistance evolution, specifically using next generation sequencing (NGS) can potentially inform care, but remains understudied, particularly in antiretroviral therapy (ART)-experienced CALWH in resource-limited settings. We conducted reverse-transcriptase NGS and investigated short-and long-term resistance evolution and its predicted impact in a well-characterized cohort of Kenyan CALWH failing 1st-line ART and followed for up to ~8 years. Drug resistance mutation (DRM) evolution types were determined by NGS frequency changes over time, defined as evolving (up-trending and crossing the 20% NGS threshold), reverting (down-trending and crossing the 20% threshold) or other. Exploratory analyses assessed potential impacts of minority resistance variants on evolution. Evolution was detected in 93% of 42 participants, including 91% of 22 with short-term follow-up, 100% of 7 with long-term follow-up without regimen change, and 95% of 19 with long-term follow-up with regimen change. Evolving DRMs were identified in 60% and minority resistance variants evolved in 17%, with exploratory analysis suggesting greater rate of evolution of minority resistance variants under drug selection pressure and higher predicted drug resistance scores in the presence of minority DRMs. Despite high-level pre-existing resistance, NGS-based longitudinal follow-up of this small but unique cohort of Kenyan CALWH demonstrated continued DRM evolution, at times including low-level DRMs detected only by NGS, with predicted impact on care. NGS can inform better understanding of DRM evolution and dynamics and possibly improve care. The clinical significance of these findings should be further evaluated.

Indexed as

Anti-HIV AgentsHIV-1HIV InfectionsHIV SeropositivityAdolescentCardiomyopathiesChildDrug Resistance, ViralGenotypeHigh-Throughput Nucleotide SequencingHumansKenyaMuscular DystrophiesMutationAnti-HIV Agentschildren and adolescentsevolution of drug resistanceHIV-1 drug resistanceminority drug resistance variantstypes of drug resistance evolution

Identifiers

PMID37515104
PMCPMC10383797
OpenAlexW4381798799

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.