Evidence map›Paper›PMID 39960813›Full record

ArticlePharmacogenetics and genomics2025

Pharmacogenetics of plasma dolutegravir exposure during 1-month rifapentine/isoniazid treatment of latent tuberculosis.

Nia Covington, Anne F Luetkemeyer, Marjorie Z Imperial, Rodney Dawson, Yoninah Cramer, Sue Rosenkranz, Susan Swindells, Irina Gelmanova, Anchalee Avihingsanon, Roberto C Arduino and 5 more

Abstract read
In one paragraph

Article in Pharmacogenetics and genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
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

15 authors.

Nia CovingtonCollege of Charleston, Charleston, South Carolina.
Anne F LuetkemeyerUniversity of California San Francisco, San Francisco, California, USA.
Marjorie Z ImperialUniversity of California San Francisco, San Francisco, California, USA.
Rodney DawsonUniversity of Cape Town, Cape Town, South Africa.
Yoninah CramerFrontier Science Foundation, Brookline, Massachusetts.
Sue RosenkranzFrontier Science Foundation, Brookline, Massachusetts.
Susan SwindellsUniversity of Nebraska Medical Center, Omaha, Nebraska.
Irina GelmanovaNational Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
Anchalee AvihingsanonThai Red Cross AIDS Research Centre, Bangkok, Thailand.
Roberto C ArduinoMcGovern Medical School at UTHealth, Houston, Texas, USA.
Wadzanai SamanekaUniversity of Zimbabwe, Harare, Zimbabwe.
Kelly E DooleyVanderbilt University Medical Center.
Rada SavicUniversity of California San Francisco, San Francisco, California, USA.
Anthony T PodanyUniversity of Nebraska Medical Center, Omaha, Nebraska.
David W HaasVanderbilt University Medical Center.

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
Vanderbilt Institute for Clinical and Translational Research (VICTR) -Identifying correlates of functional immunity in SARS-CoV-2 convalescent plasmaUL1TR002243 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Paul A. Harris, Wesley H Self · 2017 to 2026
$130.7M
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
Clinical and Translational Science InstituteUL1TR001872 · NCATS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI COLLARD, HAROLD R, JACOBY, VANESSA · 2016 to 2025
$112.1M
UZ-UCSF CTUUM1AI069436 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ZVAVAHERA MIKE CHIRENJE, LYNDA STRANIX-CHIBANDA · 2012 to 2026
$75.9M
University of North Carolina Global HIV Prevention and Treatment Clinical Trials Unit 2024 SupplementUM1AI069423 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, MINA CHRISTINE HOSSEINIPOUR · 2012 to 2026
$71.8M
UCSD Department of Medicine HIV/AIDS Clinical Trials UnitUM1AI069432 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TIMOTHY J. WILKIN · 2012 to 2026
$50.4M
UZ-UCSF Clinical Trials UnitU01AI069436 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHIRENJE, ZVAVAHERA MIKE · 2007 to 2011
$49.3M
University of Cape Town Clinical Trials Unit (UCTCTU)UM1AI069519 · NIAID · UNIVERSITY OF CAPE TOWN · PI Linda-Gail Bekker · 2012 to 2026
$36.3M
Vanderbilt HIV Clinical Trials Unit (CTU)UM1AI069439 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI David W Haas, Spyros A Kalams · 2012 to 2026
$33.1M
San Francisco Vaccine and Prevention UnitUM1AI069496 · NIAID · PUBLIC HEALTH FOUNDATION ENTERPRISES · PI Susan Buchbinder, Diane V Havlir · 2012 to 2026
$30.5M
NCATS NIH HHS UL1 TR001872NCATS NIH HHS UL1 TR002243NIAID NIH HHS K23 AI134307NIAID NIH HHS K24 AI150349NIAID NIH HHS P30 AI110527NIAID NIH HHS R01 AI077505NIAID NIH HHS R01 AI120790NIAID NIH HHS U01 AI069399NIAID NIH HHS U01 AI069421NIAID NIH HHS U01 AI069423NIAID NIH HHS U01 AI069432NIAID NIH HHS U01 AI069436NIAID NIH HHS U01 AI069439NIAID NIH HHS U01 AI069456NIAID NIH HHS U01 AI069496NIAID NIH HHS U01 AI069519NIAID NIH HHS UM1 AI068634NIAID NIH HHS UM1 AI068636NIAID NIH HHS UM1 AI069399NIAID NIH HHS UM1 AI069421NIAID NIH HHS UM1 AI069423NIAID NIH HHS UM1 AI069432NIAID NIH HHS UM1 AI069436NIAID NIH HHS UM1 AI069439NIAID NIH HHS UM1 AI069456NIAID NIH HHS UM1 AI069496NIAID NIH HHS UM1 AI069519NIAID NIH HHS UM1 AI106701
6 · The paper itself

Abstract

In Advancing Clinical Therapeutics Globally protocol A5372, a pharmacokinetic study of dolutegravir with 1-month of daily rifapentine/isoniazid, twice-daily dolutegravir offset the induction effects of rifapentine on plasma dolutegravir trough concentrations (C trough ). Here, we characterize the impact on dolutegravir C trough of UGT1A1 , AADAC , and NAT2 polymorphisms that affect dolutegravir, rifapentine, and isoniazid, respectively. People with HIV receiving dolutegravir-based antiretroviral therapy with an indication to treat latent tuberculosis underwent pharmacokinetic sampling during dolutegravir 50 mg once daily alone, and on day 28 of dolutegravir 50 mg twice daily with rifapentine/isoniazid. Multivariable linear regression models characterized genetic associations with dolutegravir C trough . Among 30 participants evaluable for genetic associations, median (Q1, Q3) day 0 dolutegravir C trough was 1745 (1099, 2694) ng/ml, and day 28 was 2146 (1412, 2484) ng/ml. Day 28 C trough was higher with UGT1A1 rs887829 TT [geometric mean ratio (GMR) = 1.65; 90% confidence interval (CI): 0.97-2.78] and CT (GMR = 1.38; 90% CI: 1.02-1.86) than with CC, and was higher with AADAC rs1803155 GG (GMR = 1.79; 90% CI: 1.09-2.93) and AG (GMR = 1.48; 90% CI: 1.14-1.90) than with AA. Median day 28 C trough ranged from 1205 (1063, 1897) ng/ml with 4 total UGT1A1 and AADAC risk alleles, to 3882 and 3717 ng/ml with only one risk allele. Individuals with concomitant AADAC slow metabolizer and UGT1A1 normal metabolizer genotypes may be at greater risk for clinically significant drug-drug interactions between rifapentine/isoniazid and dolutegravir.

Indexed as

Carboxylic Ester HydrolasesGlucuronosyltransferaseHIV InfectionsHIV Integrase InhibitorsLatent TuberculosisAdultAntibiotics, AntitubercularDolutegravirFemaleHeterocyclic Compounds, 3-RingHumansIsoniazidMaleMiddle AgedOxazinesPharmacogenomic TestingAADAC protein, humanAntibiotics, AntitubercularCarboxylic Ester HydrolasesDolutegravirGlucuronosyltransferaseHeterocyclic Compounds, 3-RingHIV Integrase InhibitorsIsoniazidOxazinesPiperazinesPyridonesRifampinrifapentineUGT1A1 EnzymeCYP3AdolutegravirHIV-1isoniazidpharmacogeneticsrifapentinetuberculosisUGT1A1

Identifiers

PMID39960813
PMCPMC12043259

What Socratic holds

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Registered trials

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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 Socratic graph.