Trial reportJournal of acquired immune deficiency syndromes (1999)2012
Concomitant efavirenz reduces pharmacokinetic exposure to the antimalarial drug artemether-lumefantrine in healthy volunteers.
Trial report in Journal of acquired immune deficiency syndromes (1999), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 3 of them syntheses 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
24 citing papers in PubMed, 3 syntheses or guidelines pooled it, 52 citations in OpenAlex.
- An Individual Participant Data Population Pharmacokinetic Meta-analysis of Drug-Drug Interactions between Lumefantrine and Commonly Used Antiretroviral Treatment.Antimicrobial agents and chemotherapy · 2020Pooled it
- Pooled it
- Pooled it
- Artemether-lumefantrine efficacy among adults on antiretroviral therapy in Malawi.Malaria journal · 2023Trial
- Trial
- Impact of Efavirenz-, Ritonavir-Boosted Lopinavir-, and Nevirapine-Based Antiretroviral Regimens on the Pharmacokinetics of Lumefantrine and Safety of Artemether-Lumefantrine in Plasmodium falciparum-Negative HIV-Infected Malawian Adults Stabilized on Antiretroviral Therapy.Antimicrobial agents and chemotherapy · 2018Trial
- Artemether-lumefantrine co-administration with antiretrovirals: population pharmacokinetics and dosing implications.British journal of clinical pharmacology · 2015Trial
- Artemisinin-based combination therapies are efficacious and safe for treatment of uncomplicated malaria in HIV-infected Ugandan children.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2014Trial
- Impact of Dolutegravir-, Lopinavir/Ritonavir-, and Efavirenz-Based Antiretrovirals on Piperaquine Pharmacokinetics in Ugandan Children Living with HIV.Clinical pharmacology and therapeutics · 2026Article
- Impact of Drug Exposure on Resistance Selection Following Artemether-Lumefantrine Treatment for Malaria in Children With and Without HIV in Uganda.Clinical pharmacology and therapeutics · 2023Article
- Health Considerations for HIV-Infected International Travelers.Current infectious disease reports · 2019Review
- Drug Interactions between Dolutegravir and Artemether-Lumefantrine or Artesunate-Amodiaquine.Antimicrobial agents and chemotherapy · 2019Article
- Article
- Strong correlation of lumefantrine concentrations in capillary and venous plasma from malaria patients.PloS one · 2018Article
- Concomitant nevirapine impacts pharmacokinetic exposure to the antimalarial artemether-lumefantrine in African children.PloS one · 2017Article
- Antiretroviral Choice for HIV Impacts Antimalarial Exposure and Treatment Outcomes in Ugandan Children.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2016Article
- CYP2B6*6 genotype and high efavirenz plasma concentration but not nevirapine are associated with low lumefantrine plasma exposure and poor treatment response in HIV-malaria-coinfected patients.The pharmacogenomics journal · 2016Article
- Artemether-Lumefantrine Exposure in HIV-Infected Nigerian Subjects on Nevirapine-Containing Antiretroviral Therapy.Antimicrobial agents and chemotherapy · 2015Article
- The influence of nevirapine and efavirenz-based anti-retroviral therapy on the pharmacokinetics of lumefantrine and anti-malarial dose recommendation in HIV-malaria co-treatment.Malaria journal · 2015Article
- The epidemiological impact of HIV antiretroviral therapy on malaria in children.AIDS (London, England) · 2015Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe antiretroviral drug efavirenz (EFV) and the antimalarial artemisinin-based combination therapy artemether-lumefantrine (AL) are commonly co-administered to treat HIV and malaria. EFV is a known inducer of cytochrome P450 3A4, which converts artemether to dihydroartemisinin (DHA) that is also active and metabolizes longer acting lumefantrine (LR). A study in healthy volunteers was completed to address the concern that EFV impacts AL pharmacokinetics (PKs).
methodsAdults received AL (80/480 mg twice daily) for 3-days before and during EFV co-administration (600 mg daily for 26 days) with intensive PK for artemether, DHA, and LR conducted after the last AL dose for each period. EFV PK was evaluated with and without AL. PK parameters were estimated using noncompartmental methods.
resultsTwelve subjects completed the 2-period study. PK exposure for artemether, DHA, and LR [as estimated by the area under the concentration time curve (AUClast)] decreased or trended toward decrease with EFV, compared with when administered alone [-51% (P = 0.084), -46% (P = 0.005), and -21% (P = 0.102), respectively]. Day-7 LR levels, previously deemed predictive of treatment success, were 46% lower (P = 0.002) with EFV, but the LR half-life was unchanged. EFV PK exposure was minimally altered after AL co-administration [AUC0-24 hrs decreased by 17% (P = 0.034)].
conclusionsExposure to DHA, but not LR, was significantly lower during EFV-AL co-administration compared with that during administration of AL alone. These findings may have implications for the treatment efficacy of AL, particularly in children. However, the observed modest changes probably do not warrant dosage adjustment during co-administration of AL with EFV.
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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.