Evidence map›Paper›PMID 34910844›Full record

ArticleJournal of the International AIDS Society2021

Tenofovir diphosphate levels in dried blood spots are associated with virologic failure and resistance to first-line therapy in South Africa: a case-control cohort study.

Jose R Castillo-Mancilla, Johnathan A Edwards, Jaysingh Brijkumar, Mahomed-Yunus Moosa, Yuan Zhao, Igho Ofotokun, Brent A Johnson, Mitchell H Lee, Selvan Pillay, Melendhran Pillay and 7 more

Open access · goldAbstract read
In one paragraph

Article in Journal of the International AIDS Society, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.5field-weighted citation impact, top 33% 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

9 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Observational
  5. Article
  6. Observational
  7. Article
  8. Article
  9. 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

17 authors at 5 institutions in 3 countries.

Jose R Castillo-MancillaDivision of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.ORCID 0000-0003-1242-1745
Johnathan A EdwardsDivision of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
Jaysingh BrijkumarNational Health Laboratory Service, Durban, South Africa.ORCID 0000-0002-3511-2112
Mahomed-Yunus MoosaNational Health Laboratory Service, Durban, South Africa.ORCID 0000-0001-8409-4689
Yuan ZhaoDivision of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
Igho OfotokunDivision of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
Brent A JohnsonDepartment of Biostatistics and Computational Biology, University of Rochester, Rochester, New York, USA.
Mitchell H LeeDivision of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
Selvan PillayNational Health Laboratory Service, Durban, South Africa.
Melendhran PillayNational Health Laboratory Service, Durban, South Africa.
Pravi MoodleyNational Health Laboratory Service, Durban, South Africa.
Daniel R KuritzkesDivison of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Henry SunpathNational Health Laboratory Service, Durban, South Africa.
Lane R BushmanDivision of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Lucas EllisonDivision of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Peter L AndersonDivision of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Vincent C MarconiDivision of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
National Health Laboratory Service · ZAEmory University · USUniversity of Colorado Anschutz Medical Campus · USBrigham and Women's Hospital · USUniversity of Rochester · US

Funding

Virology and Molecular Biomarkers CoreP30AI050409 · NIAID · EMORY UNIVERSITY · PI Ann M Chahroudi, Colleen F Kelley · 2002 to 2026
$74.0M
New Pharmacologic Measures of ART Adherence and Exposure: Pathway to Clinical ImplementationR01AI145453 · NIAID · UNIVERSITY OF COLORADO DENVER · PI ANDERSON, PETER L. · 2019 to 2023
$3.7M
Novel virologic and pharmacologic assays to predict clinical outcomes after first-line ART failure in sub-Saharan AfricaR01AI138801 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI LI, JONATHAN · 2018 to 2021
$3.2M
Antiretroviral drug resistance in KwaZulu NatalR01AI098558 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI KURITZKES, DANIEL R., MARCONI, VINCENT CHARLES · 2013 to 2017
$2.3M
NIAID NIH HHS P30 AI050409NIAID NIH HHS R01 AI098558NIAID NIH HHS R01 AI138801NIAID NIH HHS R01 AI145453
6 · The paper itself

Abstract

introductionTenofovir diphosphate (TFV-DP) in dried blood spots (DBS), a measure of cumulative antiretroviral therapy (ART) adherence, is associated with viral suppression and predicts future viremia in persons with HIV (PWH). However, its utility to identify those at risk for virologic failure (VF) and drug resistance is unknown. To address this, we aimed to establish the association between this adherence biomarker and VF with drug resistance in a cohort of PWH initiating first-line ART in KwaZulu-Natal, South Africa.

methodsPWH initiating TFV disoproxil fumarate (TDF)-based ART within a parent prospective cohort were evaluated. Using a nested design, DBS for TFV-DP were collected from cases who developed VF (HIV-1 RNA ≥1000 copies/ml) after ≥5 months on ART versus controls, matched 1:2 by site, age, gender, race and ART duration. Cases were categorized as having VF with or without resistance using genotyping. One-way analysis of variance (ANOVA) was used to compare TFV-DP for controls, cases with VF and resistance, and cases with VF without resistance. Data are presented as mean (standard deviation, SD) or geometric mean [95% confidence interval, 95% CI]. RESULTS AND DISCUSSION: One thousand participants were enrolled in the parent study between 2014 and 2016, of which 288 (29%) had DBS available. Of these, 94 (33%) were cases and 194 (67%) were controls; 59% were women. Mean age of our population was 33 (SD 8) years. Genotyping was available in 50 (53%) of the 94 cases. Geometric mean TFV-DP in DBS from controls was 708 [95% CI; 647-773] fmol/punch, which was higher compared to participants having VF with resistance (n = 36), 386 [95% CI; 241-617] fmol/punch and VF without resistance (n = 14), 61 [95% CI; 22-164] fmol/punch; p<0.001. Genotype could not be obtained in 44 (47%) cases.

conclusionsTFV-DP in DBS showed a stepwise association with VF and drug resistance in South African PWH. Participants having VF with resistance had mid-range concentrations of TFV-DP, which were higher than those for PWH without resistance. Future research on the clinical utility of TFV-DP concentrations in DBS to predict and prevent the development of VF and drug resistance is needed.

Indexed as

Anti-HIV AgentsHIV InfectionsAdenineAdultCase-Control StudiesFemaleHumansOrganophosphatesProspective StudiesSouth AfricaAdenineAnti-HIV AgentsOrganophosphatestenofovir diphosphateadherencedried blood spotsHIV resistanceSouth Africatenofovir diphosphateviral failure

Identifiers

PMID34910844
PMCPMC8673924
OpenAlexW4200587416

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.