Evidence map›Paper›PMID 35512135›Full record

ArticleThe Journal of infectious diseases2022

Pharmacogenetics of Dolutegravir Plasma Exposure Among Southern Africans With Human Immunodeficiency Virus.

Zinhle Cindi, Aida N Kawuma, Gary Maartens, Yuki Bradford, Francois Venter, Simiso Sokhela, Nomathemba Chandiwana, Roeland E Wasmann, Paolo Denti, Lubbe Wiesner and 3 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of infectious diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
1.3field-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

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Observational
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. 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

13 authors at 4 institutions in 2 countries.

Zinhle CindiDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Aida N KawumaDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Gary MaartensDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.ORCID 0000-0003-3080-6606
Yuki BradfordDepartment of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Francois VenterEzintsha, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Simiso SokhelaEzintsha, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Nomathemba ChandiwanaEzintsha, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Roeland E WasmannDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Paolo DentiDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.ORCID 0000-0001-7494-079X
Lubbe WiesnerDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.ORCID 0000-0002-9070-8699
Marylyn D RitchieDepartment of Genetics and Institute for Biomedical Informatics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
David W HaasDepartment of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Phumla SinxadiDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.ORCID 0000-0002-1312-3523
University of Cape Town · ZAUniversity of the Witwatersrand · ZAUniversity of Pennsylvania · USMeharry Medical College · US

Funding

Leadership and Operations Center (LOC), AIDS Clinical Trials Group (ACTG); LOC 1/UM1AI068636 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, RAJESH T GANDHI · 2011 to 2026
$1073.1M
Statistical and Data Management Center (SDMC), AIDS Clinical Trials Group (ACTG)UM1AI068634 · NIAID · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Marlene Ann Cooper, Michael David Hughes · 2011 to 2026
$246.6M
Validation, CLIA and Qualification (VQC): Enhancing the RS ratio as a tool for AIDS Clinical Trial Group (ACTG) tuberculosis trialsUM1AI106701 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Grace M Aldrovandi · 2014 to 2026
$116.8M
The Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR000445 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERNARD, GORDON RAPHAEL · 2012 to 2016
$41.4M
Tennessee CFAR: Implementation of Culturally Responsive Trauma-Informed Care with Youth with HIV in Memphis, TNP30AI110527 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Chandravanu Dash · 2015 to 2026
$27.5M
Pharmacogenomics of HIV TherapyR01AI077505 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI HAAS, DAVID W · 2008 to 2025
$12.3M
HIV-associated Tuberculosis Training Program (HATTP)D43TW010559 · FIC · UNIVERSITY OF CAPE TOWN · PI Graeme Ayton Meintjes · 2017 to 2026
$3.0M
FIC NIH HHS D43 TW010559NCATS NIH HHS UL1 TR000445NIAID NIH HHS P30 AI110527NIAID NIH HHS R01 AI077505NIAID NIH HHS UM1 AI068634NIAID NIH HHS UM1 AI068636NIAID NIH HHS UM1 AI106701Wellcome Trust 212265Wellcome Trust 212265/Z/18/Z
6 · The paper itself

Abstract

backgroundDolutegravir is a component of preferred antiretroviral therapy (ART) regimens. We characterized the pharmacogenetics of dolutegravir exposure after ART initiation in the ADVANCE trial in South Africa.

methodsGenome-wide genotyping followed by imputation was performed. We developed a population pharmacokinetic model for dolutegravir using nonlinear mixed-effects modeling. Linear regression models examined associations with unexplained variability in dolutegravir area under the concentration-time curve (AUCVAR).

resultsGenetic associations were evaluable in 284 individuals. Of 9 polymorphisms previously associated with dolutegravir pharmacokinetics, the lowest P value with AUCVAR was UGT1A1 rs887829 (P = 1.8 × 10-4), which was also associated with log10 bilirubin (P = 8.6 × 10-13). After adjusting for rs887829, AUCVAR was independently associated with rs28899168 in the UGT1A locus (P = .02), as were bilirubin concentrations (P = 7.7 × 10-8). In the population pharmacokinetic model, rs887829 T/T and C/T were associated with 25.9% and 10.8% decreases in dolutegravir clearance, respectively, compared with C/C. The lowest P value for AUCVAR genome-wide was CAMKMT rs343942 (P = 2.4 × 10-7).

conclusionsIn South Africa, rs887829 and rs28899168 in the UGT1A locus were independently associated with dolutegravir AUCVAR. The novel rs28899168 association warrants replication. This study enhances understanding of dolutegravir pharmacogenetics in Africa.

Indexed as

HIV InfectionsPharmacogeneticsBilirubinDolutegravirHeterocyclic Compounds, 3-RingHIVHumansPyridonesSouth AfricaBilirubinDolutegravirHeterocyclic Compounds, 3-RingPyridonesantiretroviral therapydolutegravirHIVpharmacogeneticspharmacokinetics

Identifiers

PMID35512135
PMCPMC9624457
OpenAlexW4229011579

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.