Evidence map›Paper›PMID 30815689›Full record

ArticleThe Journal of antimicrobial chemotherapy2019

Rifampicin effect on intracellular and plasma pharmacokinetics of tenofovir alafenamide.

Maddalena Cerrone, Omamah Alfarisi, Megan Neary, Mark A Marzinke, Teresa L Parsons, Andrew Owen, Gary Maartens, Anton Pozniak, Charles Flexner, Marta Boffito

Open access · greenAbstract readClinical Trial, Phase I
In one paragraph

Article in The Journal of antimicrobial chemotherapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 2 pooled it
4.6field-weighted citation impact, top 4% 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

30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 62 citations in OpenAlex.

  1. Pooled it
  2. Guideline
  3. Twice-Daily Dolutegravir-Based Antiretroviral Therapy With 1 Month of Daily Rifapentine and Isoniazid for Tuberculosis Prevention.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024
    Trial
  4. HBV/HCV coinfection and anti-tuberculosis drug-induced liver injury: from risk assessment and exploration of mechanisms to preventive considerations.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026
    Review
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  15. Epidemiology, pathogenesis, clinical presentation and management of TB in patients with HIV and diabetes.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2023
    Article
  16. Tenofovir Alafenamide Plasma Concentrations Are Reduced in Pregnant Women Living With Human Immunodeficiency Virus (HIV): Data From the PANNA Network.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022
    Article
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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 4 institutions in 3 countries.

Maddalena CerroneSt Stephen's AIDS Trust, Chelsea and Westminster Hospital, London, UK.
Omamah AlfarisiJohns Hopkins University, Baltimore, MD, USA.
Megan NearyMolecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Mark A MarzinkeJohns Hopkins University, Baltimore, MD, USA.
Teresa L ParsonsJohns Hopkins University, Baltimore, MD, USA.
Andrew OwenMolecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
Gary MaartensDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Anton PozniakSt Stephen's AIDS Trust, Chelsea and Westminster Hospital, London, UK.
Charles FlexnerJohns Hopkins University, Baltimore, MD, USA.
Marta BoffitoSt Stephen's AIDS Trust, Chelsea and Westminster Hospital, London, UK.
Johns Hopkins University · USChelsea and Westminster Hospital · GBUniversity of Liverpool · GBUniversity of Cape Town · ZA

Funding

Vaccine Response and Immunotherapeutics SWGP30AI094189 · NIAID · JOHNS HOPKINS UNIVERSITY · PI Anna Palmer Durbin · 2012 to 2026
$67.0M
NIAID NIH HHS P30 AI094189
6 · The paper itself

Abstract

objectivesTenofovir alafenamide produces lower plasma tenofovir and higher intracellular tenofovir diphosphate (DP) concentrations than tenofovir disoproxil fumarate but it is likely a victim of interactions with rifampicin. We aimed to investigate the pharmacokinetics of tenofovir alafenamide/emtricitabine with rifampicin. PATIENTS AND

methodsHealthy volunteers received tenofovir alafenamide/emtricitabine at 25/200 mg once daily, followed by tenofovir alafenamide/emtricitabine + rifampicin daily followed by tenofovir disoproxil fumarate. Plasma tenofovir alafenamide, tenofovir, emtricitabine and intracellular tenofovir-DP and emtricitabine triphosphate pharmacokinetics and genetic polymorphisms were assessed.

resultsTenofovir alafenamide exposure decreased when tenofovir alafenamide/emtricitabine + rifampicin was used compared with tenofovir alafenamide/emtricitabine [geometric mean ratio (GMR) (90% CI): 0.45 (0.33-0.60)]. Plasma tenofovir and intracellular tenofovir-DP concentrations decreased with rifampicin [GMR (90% CI): 0.46 (0.40-0.52) and 0.64 (0.54-0.75), respectively]. GMR (90% CI) of intracellular tenofovir-DP AUC0-24 for tenofovir alafenamide/emtricitabine + rifampicin versus tenofovir disoproxil fumarate was 4.21 (2.98-5.95). Rifampicin did not affect emtricitabine pharmacokinetics. CYP3A4*22 rs35599367 was associated with higher plasma tenofovir alafenamide AUC0-24 at day 56.

conclusionsFollowing tenofovir alafenamide/emtricitabine administration with rifampicin, intracellular tenofovir-DP concentrations were still 4.21-fold higher than those achieved by tenofovir disoproxil fumarate, supporting further study during HIV/TB co-infection.

Indexed as

AdenineAdultAntibiotics, AntitubercularAnti-HIV AgentsAntiviral AgentsDrug InteractionsDrug Resistance, ViralFemaleHumansMaleMiddle AgedOrganophosphatesPharmacogenomic TestingRifampinTissue DistributionYoung AdultAdenineAntibiotics, AntitubercularAnti-HIV AgentsAntiviral AgentsOrganophosphatesRifampintenofovir diphosphate

Identifiers

PMID30815689
PMCPMC8204702
OpenAlexW2918499676

What Socratic holds

Textmetadata
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 Socratic graph.