Evidence map›Paper›PMID 37982585›Full record

ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2024

Pharmacokinetics and Safety of Twice-daily Ritonavir-boosted Atazanavir With Rifampicin.

Kamunkhwala Gausi, Henry Mugerwa, Marco Siccardi, Maiara Camotti Montanha, Mohammed Lamorde, Lubbe Wiesner, Antonio D'Avolio, Helen McIlleron, Edmund Wilkins, Amedeo De Nicolò and 5 more

Registry-linked trialOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04121195 (A Phase 3, Open-label, Dose Escalation Study to Determine the Pharmacokinetics of Atazanavir Administered With RIfampicin to HIV Positive Adults on sEcond-line ART Regimen With Suppressed HIV-1 Viral Load), which is not on this map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.7field-weighted citation impact, top 15% 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.

NCT04121195 phase2 / phase3completednot on this map

A Phase 3, Open-label, Dose Escalation Study to Determine the Pharmacokinetics of Atazanavir Administered With RIfampicin to HIV Positive Adults on sEcond-line ART Regimen With Suppressed HIV-1 Viral Load (DERIVE)

TypeinterventionalSponsorUniversity of LiverpoolRan2020 to 2023Enrolled26ConditionsHIV/AIDS, TuberculosisArmsDose escalation
3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 9 citations in OpenAlex.

  1. Trial
  2. Observational
  3. Article
  4. Article
  5. Observational
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 at 6 institutions in 4 countries.

Kamunkhwala GausiDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.ORCID 0000-0002-9002-8087
Henry MugerwaJoint Clinical Research Centre, Research Department, Kampala, Uganda.
Marco SiccardiDepartment of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom.
Maiara Camotti MontanhaDepartment of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom.
Mohammed LamordeInfectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda.
Lubbe WiesnerDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.ORCID 0000-0002-9070-8699
Antonio D'AvolioLaboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Turin, Italy.
Helen McIlleronDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Edmund WilkinsNorth Manchester General Hospital, HIV Research Unit, Manchester, United Kingdom.
Amedeo De NicolòLaboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Turin, Italy.ORCID 0000-0002-5973-9948
Gary MaartensDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.ORCID 0000-0003-3080-6606
Saye KhooDepartment of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom.
Cissy KityoDivision 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
Catriona WaittDepartment of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom.
University of Cape Town · ZAUniversity of Liverpool · GBUniversity of Turin · ITInfectious Diseases Institute · UGJoint Clinical Research Centre · UGNorth Manchester General Hospital · GB

Funding

European Union RIA2016MC-1606-VirTUAL
6 · The paper itself

Abstract

backgroundCritical drug-drug interactions (DDI) and hepatotoxicity complicate concurrent use of rifampicin and protease inhibitors. We investigated whether dose escalation of atazanavir/ritonavir could safely overcome the DDI with rifampicin.

methodsDERIVE (NCT04121195, EDCTP) was a dose-escalation trial in people with human immunodeficiency virus (HIV) on atazanavir/ritonavir-based antiretroviral therapy (ART) in Uganda. Four intensive pharmacokinetic (PK) visits were performed: PK1 300/100 mg OD (baseline); PK2 300/100 mg OD with rifampicin 600 mg; PK3 300/100 mg twice a day (BID) with rifampicin 600 mg OD; PK4 300/100 mg BID with rifampicin 1200 mg OD. Dolutegravir 50 mg BID throughout the study period ensured participants remained protected from subtherapeutic atazanavir concentrations. The data were interpreted with noncompartmental analysis. The target minimum concentration was atazanavir's protein-adjusted IC90 (PA-IC90), 0.014 mg/L.

resultsWe enrolled 26 participants (23 female) with median (range) age 44 (28-61) years and weight 67 (50-75) kg. Compared with PK1, atazanavir Ctau, and AUC were significantly reduced at PK2 by 96% and 85%, respectively. The escalation to BID dosing (PK3) reduced this difference in Ctau, and AUC24 to 18% lower and 8% higher, respectively. Comparable exposures were maintained with double doses of rifampicin. Lowest Ctau during PK1, PK3, and PK4 were 12.7-, 4.8-, and 8.6-fold higher than PA-IC90, respectively, whereas 65% of PK2 Ctau were below the limit of quantification (0.03 mg/L), hence likely below PA-IC90. No participant developed significant elevation of liver enzymes, reported a serious adverse event (SAE) or experienced rebound viraemia.

conclusionsTwice daily atazanavir/ritonavir during rifampicin co-administration was well tolerated and achieved plasma concentrations above the target. CLINICAL TRIALS REGISTRATION: NCT04121195. Registered on 09 October 2019, https://clinicaltrials.gov/ct2/show/NCT04121195.

Indexed as

Atazanavir SulfateDrug InteractionsHIV InfectionsRifampinRitonavirAdultAnti-HIV AgentsDrug Administration ScheduleDrug Therapy, CombinationFemaleHIV Protease InhibitorsHumansMaleMiddle AgedUgandaAnti-HIV AgentsAtazanavir SulfateHIV Protease InhibitorsRifampinRitonavirAfrica CID specificationsdrug-drug interactionHIVpharmacokineticstuberculosis

Identifiers

PMID37982585
PMCPMC11093668
OpenAlexW4388826069

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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.