2024
Persistent and multiclonal malaria parasite dynamics despite extended artemether-lumefantrine treatment in children
Goodwin J, Kajubi R, Wang K, Li F, Wade M, Orukan F, Huang L, Whalen M, Aweeka F, Mwebaza N, Parikh S. Persistent and multiclonal malaria parasite dynamics despite extended artemether-lumefantrine treatment in children. Nature Communications 2024, 15: 3817. PMID: 38714692, PMCID: PMC11076639, DOI: 10.1038/s41467-024-48210-7.Peer-Reviewed Original ResearchMeSH KeywordsAntimalarialsArtemether, Lumefantrine Drug CombinationArtemisininsChildChild, PreschoolFemaleHIV InfectionsHumansInfantMalariaMalaria, FalciparumMaleParasitemiaPlasmodium falciparumRNA, Ribosomal, 18SConceptsDay 7 lumefantrine concentrationsArtemether-lumefantrine treatmentRing-stage parasitesEarly post-treatmentEarly post-treatment periodArtemether-lumefantrineArtemisinin resistanceDay regimenMulticlonal infectionsEfficacious therapyFollow-upRandomized trialsPersistent clonesTransmission settingsEffective treatmentPost-treatment periodRegimensAntimalarial studiesStandard diagnosticsStandard 3DaysPost-treatmentChildrenTreatmentTherapy
2023
Artemether-lumefantrine efficacy among adults on antiretroviral therapy in Malawi
Nyangulu W, Mungwira R, Divala T, Nampota-Nkomba N, Nyirenda O, Buchwald A, Miller J, Earland D, Adams M, Plowe C, Taylor T, Mallewa J, van Oosterhout J, Parikh S, Laurens M, Laufer M. Artemether-lumefantrine efficacy among adults on antiretroviral therapy in Malawi. Malaria Journal 2023, 22: 32. PMID: 36707795, PMCID: PMC9881508, DOI: 10.1186/s12936-023-04466-w.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntimalarialsArtemetherArtemether, Lumefantrine Drug CombinationArtemisininsDrug CombinationsEthanolaminesFluorenesHIV InfectionsHumansLumefantrineMalariaMalaria, FalciparumMalawiTreatment OutcomeConceptsAntiretroviral therapyLumefantrine levelsTreatment failureDrug-drug interactionsACPR ratesMalaria infectionTrimethoprim-sulfamethoxazolePCR correctionTreatment efficacyUndetectable HIV RNA viral loadEfavirenz-based antiretroviral therapyHIV RNA viral loadUncomplicated Plasmodium falciparum malariaHuman immunodeficiency virus (HIV) infectionArtemether-lumefantrine efficacyCohort of PWHEfavirenz-based regimensImmunodeficiency virus infectionRNA viral loadPlasmodium falciparum malariaMalaria treatment failurePopulation of adultsRandom-effects modelTherapeutic efficacy monitoringLumefantrine exposure
2022
Impact of Drug Exposure on Resistance Selection Following Artemether‐Lumefantrine Treatment for Malaria in Children With and Without HIV in Uganda
Kay K, Goodwin J, Ehrlich H, Ou J, Freeman T, Wang K, Li F, Wade M, French J, Huang L, Aweeka F, Mwebaza N, Kajubi R, Riggs M, Ruiz‐Garcia A, Parikh S. Impact of Drug Exposure on Resistance Selection Following Artemether‐Lumefantrine Treatment for Malaria in Children With and Without HIV in Uganda. Clinical Pharmacology & Therapeutics 2022, 113: 660-669. PMID: 36260349, PMCID: PMC9981240, DOI: 10.1002/cpt.2768.Peer-Reviewed Original ResearchMeSH KeywordsAntimalarialsArtemetherArtemether, Lumefantrine Drug CombinationArtemisininsChildDrug CombinationsFluorenesHIV InfectionsHumansLopinavirLumefantrineMalariaMalaria, FalciparumNevirapineRitonavirUgandaConceptsLopinavir-ritonavirLumefantrine concentrationsSensitive parasitesRecurrence riskPopulation PK/PD modelArtemether-lumefantrine treatmentTrimethoprim-sulfamethoxazole prophylaxisPK/PD modelPopulation PK modelFirst-order absorptionHigh transmission regionsAntiretroviral regimensLumefantrine exposureLumefantrine susceptibilityPfcrt K76Pfmdr1 N86Suboptimal dosingArtemether-lumefantrineTwo-compartment modelHIV statusRecurrent infectionsCombination therapyDrug exposurePrimary treatmentArtemisinin resistanceThe Impact of Extended Treatment With Artemether-lumefantrine on Antimalarial Exposure and Reinfection Risks in Ugandan Children With Uncomplicated Malaria: A Randomized Controlled Trial
Whalen ME, Kajubi R, Goodwin J, Orukan F, Colt M, Huang L, Richards K, Wang K, Li F, Mwebaza N, Aweeka FT, Parikh S. The Impact of Extended Treatment With Artemether-lumefantrine on Antimalarial Exposure and Reinfection Risks in Ugandan Children With Uncomplicated Malaria: A Randomized Controlled Trial. Clinical Infectious Diseases 2022, 76: 443-452. PMID: 36130191, PMCID: PMC9907485, DOI: 10.1093/cid/ciac783.Peer-Reviewed Original ResearchMeSH KeywordsAntimalarialsArtemetherArtemether, Lumefantrine Drug CombinationArtemisininsChildChild, PreschoolDrug CombinationsEthanolaminesFluorenesHumansInfantLumefantrineMalariaMalaria, FalciparumParasitemiaProspective StudiesReinfectionUgandaConceptsArtemether-lumefantrineReinfection riskArtemisinin-based combination therapyDay 7 levelsOverall drug exposureHigh transmission settingsYoung childrenAntimalarial exposureUncomplicated malariaExtended regimenRecurrent parasitemiaControlled TrialsPrimary outcomeCombination therapyKaplan-MeierDrug exposureTotal episodesUgandan childrenArtemisinin resistanceLumefantrine concentrationsPharmacodynamic studiesHigh riskPharmacokinetic parametersRecurrence riskDay 7
2020
An Individual Participant Data Population Pharmacokinetic Meta-analysis of Drug-Drug Interactions between Lumefantrine and Commonly Used Antiretroviral Treatment
Francis J, Barnes KI, Workman L, Kredo T, Vestergaard LS, Hoglund RM, Byakika-Kibwika P, Lamorde M, Walimbwa SI, Chijioke-Nwauche I, Sutherland CJ, Merry C, Scarsi KK, Nyagonde N, Lemnge MM, Khoo SH, Bygbjerg IC, Parikh S, Aweeka FT, Tarning J, Denti P. An Individual Participant Data Population Pharmacokinetic Meta-analysis of Drug-Drug Interactions between Lumefantrine and Commonly Used Antiretroviral Treatment. Antimicrobial Agents And Chemotherapy 2020, 64: 10.1128/aac.02394-19. PMID: 32071050, PMCID: PMC7179577, DOI: 10.1128/aac.02394-19.Peer-Reviewed Original ResearchConceptsDrug-drug interactionsAntiretroviral therapyDolutegravir-based antiretroviral therapyPotential drug-drug interactionsDay 7 concentrationsIndividual participant dataConcomitant efavirenzLopinavir-ritonavirLumefantrine exposureLumefantrine regimenAntituberculosis treatmentUncomplicated malariaAntiretroviral treatmentHIV infectionTreatment failurePopulation pharmacokineticsLumefantrine concentrationsLarger body weightBody weightEfavirenzParticipant dataLumefantrineMalariaAdult participantsRifampinEfavirenz-Based Antiretroviral Therapy Reduces Artemether-Lumefantrine Exposure for Malaria Treatment in HIV-Infected Pregnant Women.
Hughes E, Mwebaza N, Huang L, Kajubi R, Nguyen V, Nyunt MM, Orukan F, Mwima MW, Parikh S, Aweeka F. Efavirenz-Based Antiretroviral Therapy Reduces Artemether-Lumefantrine Exposure for Malaria Treatment in HIV-Infected Pregnant Women. JAIDS Journal Of Acquired Immune Deficiency Syndromes 2020, 83: 140-147. PMID: 31929402, PMCID: PMC7061940, DOI: 10.1097/qai.0000000000002237.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAlkynesAnti-HIV AgentsAntimalarialsAnti-Retroviral AgentsArtemetherArtemether, Lumefantrine Drug CombinationArtemisininsBenzoxazinesCyclopropanesDrug CombinationsDrug InteractionsFemaleHIV InfectionsHumansLumefantrineMalariaMalaria, FalciparumPregnancyProspective StudiesUgandaYoung AdultConceptsEfavirenz-based antiretroviral therapyImpact of efavirenzPregnant womenArtemether-lumefantrineMalaria treatmentAntiretroviral therapyEfavirenz therapyIntensive PK evaluationPK exposure parametersPlasmodium falciparum malariaEffect of efavirenzActive metabolite dihydroartemisininAntimalarial exposureClinical responseFalciparum malariaPregnant HIVTreatment regimenNonsignificant reductionClinical pharmacokinetic studiesPK evaluationDrug interactionsLumefantrine concentrationsHIVTreatment durationPK samples
2018
Artemether-lumefantrine dosing for malaria treatment in young children and pregnant women: A pharmacokinetic-pharmacodynamic meta-analysis
Kloprogge F, Workman L, Borrmann S, Tékété M, Lefèvre G, Hamed K, Piola P, Ursing J, Kofoed PE, Mårtensson A, Ngasala B, Björkman A, Ashton M, Hietala S, Aweeka F, Parikh S, Mwai L, Davis TME, Karunajeewa H, Salman S, Checchi F, Fogg C, Newton PN, Mayxay M, Deloron P, Faucher JF, Nosten F, Ashley EA, McGready R, van Vugt M, Proux S, Price RN, Karbwang J, Ezzet F, Bakshi R, Stepniewska K, White NJ, Guerin PJ, Barnes KI, Tarning J. Artemether-lumefantrine dosing for malaria treatment in young children and pregnant women: A pharmacokinetic-pharmacodynamic meta-analysis. PLOS Medicine 2018, 15: e1002579. PMID: 29894518, PMCID: PMC5997317, DOI: 10.1371/journal.pmed.1002579.Peer-Reviewed Original ResearchMeSH KeywordsAntimalarialsArtemether, Lumefantrine Drug CombinationChild, PreschoolDose-Response Relationship, DrugEthanolaminesFemaleFluorenesHumansInfantInfant, NewbornMalaria, FalciparumMaleModels, ChemicalPregnancyConceptsPregnant womenArtemether-lumefantrineCure rateClinical studiesYoung childrenCurrent standard treatment regimenUncomplicated Plasmodium falciparum malariaPharmacokinetic modelAbsorption of lumefantrinePre-treatment parasitaemiaVenous plasma dataAlternative dosing regimensPlasmodium falciparum malariaStandard treatment regimenProspective clinical studyNon-pregnant adultsLow cure ratePopulation pharmacokinetic modelRelevant clinical studiesUseful therapeutic lifeFrequency of dosingConcentration-time dataHigher individual dosesLumefantrine exposureLumefantrine levels
2016
Antiretroviral Choice for HIV Impacts Antimalarial Exposure and Treatment Outcomes in Ugandan Children
Parikh S, Kajubi R, Huang L, Ssebuliba J, Kiconco S, Gao Q, Li F, Were M, Kakuru A, Achan J, Mwebaza N, Aweeka FT. Antiretroviral Choice for HIV Impacts Antimalarial Exposure and Treatment Outcomes in Ugandan Children. Clinical Infectious Diseases 2016, 63: 414-422. PMID: 27143666, PMCID: PMC4946019, DOI: 10.1093/cid/ciw291.Peer-Reviewed Original ResearchConceptsArtemether-lumefantrine treatmentLPV/rRecurrent malariaLumefantrine exposureDrug exposureCritical drug-drug interactionsFirst-line antiretroviral therapy regimensArtemisinin-based combination therapyLopinavir/ritonavirAntiretroviral therapy regimensPlasmodium falciparum malariaHuman immunodeficiency virusDay 7 concentrationsMalaria-endemic regionsDrug-drug interactionsAntimalarial exposureAntimalarial componentPharmacokinetic samplingArtemether-lumefantrineFalciparum malariaClinical outcomesDosing regimensTherapy regimensImmunodeficiency virusCombination therapy
2015
The epidemiological impact of HIV antiretroviral therapy on malaria in children
Greenhalgh S, Ndeffo M, Galvani AP, Parikh S. The epidemiological impact of HIV antiretroviral therapy on malaria in children. AIDS 2015, 29: 473-482. PMID: 25486414, PMCID: PMC4391884, DOI: 10.1097/qad.0000000000000550.Peer-Reviewed Original ResearchMeSH KeywordsAfrica South of the SaharaAnimalsAntimalarialsArtemether, Lumefantrine Drug CombinationArtemisininsChildChild, PreschoolDrug CombinationsEthanolaminesFluorenesHIV InfectionsHIV Protease InhibitorsHumansMalariaRecurrenceTreatment OutcomeConceptsHIV protease inhibitorsRecurrent malariaMalaria transmissionAntiretroviral therapyArtemether-lumefantrineAnnual incidenceProtease inhibitorsFirst-line antiretroviral regimenFirst-line antiretroviral therapyArtemether-lumefantrine treatmentHIV-negative childrenFirst-line antimalarialsHIV prevalence settingsHIV antiretroviral therapyRecent clinical trialsHIV prevalence levelsMalaria transmission settingsMalaria transmission intensityAntiretroviral regimenAntimalarial treatmentHIV prevalenceProphylactic effectPrevalence settingsClinical trialsHealth burden