Trial reportThe Journal of antimicrobial chemotherapy2020
Pharmacokinetic profile and safety of adjusted doses of darunavir/ritonavir with rifampicin in people living with HIV.
Trial report in The Journal of antimicrobial chemotherapy, 2020. 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.
What it found
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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.
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.
Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Pharmacokinetics of antiretroviral and tuberculosis drugs in children with HIV/TB co-infection: a systematic review.The Journal of antimicrobial chemotherapy · 2020Pooled it
- Model-based evaluation of the interaction between ritonavir-boosted atazanavir and rifampicin in Ugandan adults with HIV.British journal of clinical pharmacology · 2025Trial
- Safety and Pharmacokinetics of Double-Dose Lopinavir/Ritonavir + Rifampin Versus Lopinavir/Ritonavir + Daily Rifabutin for Treatment of Human Immunodeficiency Virus-Tuberculosis Coinfection.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Trial
- Population pharmacokinetics of ritonavir-boosted atazanavir in subsequent-line treatment in African children with HIV.Antimicrobial agents and chemotherapy · 2026Observational
- Intracellular Penetration of Atazanavir, Ritonavir and Dolutegravir With Concomitant Rifampicin: A Dose Escalation Study.Clinical pharmacology and therapeutics · 2025Article
- Pharmacokinetics and Safety of Twice-daily Ritonavir-boosted Atazanavir With Rifampicin.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024Article
- Pharmacokinetics, Safety, and Tolerability of Once-Daily Darunavir With Cobicistat and Weekly Isoniazid/Rifapentine.Journal of acquired immune deficiency syndromes (1999) · 2023Article
- Clinical Relevance of Drug Interactions in People Living with Human Immunodeficiency Virus on Antiretroviral Therapy-Update 2022: Systematic Review.Pharmaceutics · 2023Review
- A literature review of liver function test elevations in rifampin drug-drug interaction studies.Clinical and translational science · 2022Review
- The Effect of Rifampicin on Darunavir, Ritonavir, and Dolutegravir Exposure within Peripheral Blood Mononuclear Cells: a Dose Escalation Study.Antimicrobial agents and chemotherapy · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundDarunavir/ritonavir is better tolerated than lopinavir/ritonavir and has a higher genetic barrier to resistance. Co-administration with rifampicin has been contraindicated as a significant reduction in darunavir exposure is expected. This is a barrier to darunavir/ritonavir use where TB is endemic.
objectivesTo evaluate the safety and pharmacokinetic profile of adjusted doses of darunavir/ritonavir with rifampicin.
methodsVirally suppressed participants on second-line lopinavir/ritonavir-based ART were switched to darunavir/ritonavir 800/100 mg q24h. In sequence: rifampicin was added; the dose of ritonavir was escalated; and darunavir was increased (darunavir/ritonavir 1600/200 mg q24h and 800/100 mg q12h were given in randomized sequence with rifampicin). Darunavir plasma concentrations were measured on the seventh/last day of each treatment period. To prevent viral rebound, dolutegravir (50 mg q12h) was added during rifampicin administration and for 1 week thereafter. Clinical events, ALT and bilirubin were monitored every 2-3 days during rifampicin administration.
resultsA total of 17/28 participants started study treatment. Six (35.3%) were withdrawn for symptomatic hepatitis with severe ALT elevations, developing after 9-11 days of rifampicin and 2-4 days of ritonavir 200 mg. The study was stopped prematurely due to this high rate of hepatotoxicity. Only four participants completed the study. All hepatotoxicity resolved on withdrawal of study treatment. All participants were successfully re-established on their lopinavir/ritonavir-based regimen. After doubling the darunavir/ritonavir doses on rifampicin, darunavir pre-dose concentrations approached those on standard doses without rifampicin for q12h doses, but not for q24h doses.
conclusionsAdjusted doses of darunavir/ritonavir with rifampicin had unacceptable risk of hepatotoxicity. Darunavir trough concentrations were markedly reduced with the daily adjusted dose.
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