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 ResearchConceptsDay 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 ResearchConceptsAntiretroviral 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 ResearchConceptsLopinavir-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 resistanceClinical characteristics of Plasmodium falciparum infection among symptomatic patients presenting to a major urban military hospital in Cameroon
Hodson DZ, Mbarga Etoundi Y, Mbatou Nghokeng N, Mohamadou Poulibe R, Magne Djoko S, Goodwin J, Cheteug Nguesta G, Nganso T, Armstrong JN, Andrews JJ, Zhang E, Wade M, Eboumbou Moukoko CE, Boum Y, Parikh S. Clinical characteristics of Plasmodium falciparum infection among symptomatic patients presenting to a major urban military hospital in Cameroon. Malaria Journal 2022, 21: 298. PMID: 36273147, PMCID: PMC9588226, DOI: 10.1186/s12936-022-04315-2.Peer-Reviewed Original ResearchConceptsP. falciparum infectionPopulation attributable risk percentFalciparum infectionPlasmodium falciparum infectionYears of ageClinical characteristicsUrban hospitalMilitary HospitalAttributable risk percentHigher positivity rateLikelihood ratioRapid diagnostic testsMajor urban hospitalRural African settingConclusionsThe prevalenceHigh feverSymptomatic patientsHemoglobin levelsAnemia prevalenceSevere anemiaEmergency departmentVenous samplesClinical surveyPositivity rateWHO definitionThe 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 ResearchConceptsArtemether-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
2021
Mapping partner drug resistance to guide antimalarial combination therapy policies in sub-Saharan Africa
Ehrlich HY, Bei AK, Weinberger DM, Warren JL, Parikh S. Mapping partner drug resistance to guide antimalarial combination therapy policies in sub-Saharan Africa. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2100685118. PMID: 34261791, PMCID: PMC8307356, DOI: 10.1073/pnas.2100685118.Peer-Reviewed Original Research
2020
Efficacy and tolerability of artemisinin-based and quinine-based treatments for uncomplicated falciparum malaria in pregnancy: a systematic review and individual patient data meta-analysis
Saito M, Mansoor R, Kennon K, Anvikar AR, Ashley EA, Chandramohan D, Cohee LM, D'Alessandro U, Genton B, Gilder ME, Juma E, Kalilani-Phiri L, Kuepfer I, Laufer MK, Lwin KM, Meshnick SR, Mosha D, Mwapasa V, Mwebaza N, Nambozi M, Ndiaye JA, Nosten F, Nyunt M, Ogutu B, Parikh S, Paw MK, Phyo AP, Pimanpanarak M, Piola P, Rijken MJ, Sriprawat K, Tagbor HK, Tarning J, Tinto H, Valéa I, Valecha N, White NJ, Wiladphaingern J, Stepniewska K, McGready R, Guérin PJ. Efficacy and tolerability of artemisinin-based and quinine-based treatments for uncomplicated falciparum malaria in pregnancy: a systematic review and individual patient data meta-analysis. The Lancet Infectious Diseases 2020, 20: 943-952. PMID: 32530424, PMCID: PMC7391007, DOI: 10.1016/s1473-3099(20)30064-5.Peer-Reviewed Original ResearchConceptsArtemisinin-based combination therapyIndividual patient dataQuinine-based treatmentsUncomplicated falciparum malariaPregnant womenArtemether-lumefantrineFalciparum malariaTreatment failureOne-stage individual patient dataSystematic reviewPatient dataObservational cohort studyAcute adverse eventsClinical Trials RegistryGametocyte carriageQuinine monotherapyAsexual parasitaemiaFever clearanceAdverse eventsCohort studyParasite clearanceTreatment guidelinesTrials RegistryCombination therapyRisk factorsEfavirenz-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 AgentsAnti-Retroviral AgentsAntimalarialsArtemetherArtemether, 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
2019
Efficacy and risk of harms of repeat ivermectin mass drug administrations for control of malaria (RIMDAMAL): a cluster-randomised trial
Foy BD, Alout H, Seaman JA, Rao S, Magalhaes T, Wade M, Parikh S, Soma DD, Sagna AB, Fournet F, Slater HC, Bougma R, Drabo F, Diabaté A, Coulidiaty AGV, Rouamba N, Dabiré RK. Efficacy and risk of harms of repeat ivermectin mass drug administrations for control of malaria (RIMDAMAL): a cluster-randomised trial. The Lancet 2019, 393: 1517-1526. PMID: 30878222, PMCID: PMC6459982, DOI: 10.1016/s0140-6736(18)32321-3.Peer-Reviewed Original ResearchConceptsMass drug administrationCluster-randomised trialIntervention groupMalaria episodesControl groupDrug AdministrationDetection cohortMass administrationIvermectin mass drug administrationUncomplicated malaria episodesClinical malaria episodesMalaria transmission seasonSingle oral dosesControl of malariaAdverse eventsCumulative incidencePrimary outcomeOral dosesEligible participantsAdverse reactionsFurther dosesTwo-armExclusion criteriaTransmission seasonTreatment phase
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 ResearchConceptsPregnant 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
Malaria in HIV-Infected Children Receiving HIV Protease-Inhibitor- Compared with Non-Nucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy, IMPAACT P1068s, Substudy to P1060
Hobbs CV, Gabriel EE, Kamthunzi P, Tegha G, Tauzie J, Petzold E, Barlow-Mosha L, H. BH, Li Y, Ilmet T, Kirmse B, Neal J, Parikh S, Deygoo N, Philippe P, Mofenson L, Prescott W, Chen J, Musoke P, Palumbo P, Duffy PE, Borkowsky W, Team F. Malaria in HIV-Infected Children Receiving HIV Protease-Inhibitor- Compared with Non-Nucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy, IMPAACT P1068s, Substudy to P1060. PLOS ONE 2016, 11: e0165140. PMID: 27936233, PMCID: PMC5147802, DOI: 10.1371/journal.pone.0165140.Peer-Reviewed Original ResearchMeSH KeywordsAntimalarialsCD4 Lymphocyte CountChildChild, PreschoolCoinfectionDrug Therapy, CombinationFemaleHIV InfectionsHIV Protease InhibitorsHIV-1HumansInfantLamivudineLopinavirMalaria, FalciparumMalawiMaleNevirapinePlasmodium falciparumReverse Transcriptase InhibitorsRitonavirViral LoadZidovudineConceptsNon-nucleoside reverse transcriptase inhibitorAntiretroviral therapyReverse transcriptase inhibitorBlood smear microscopyHIV protease inhibitorsPositive BSTranscriptase inhibitorProtease inhibitorsClinical malaria incidenceMalaria parasite carriageMalaria-endemic settingsHIV antiretroviral therapyAnti-malarial treatmentLopinavir-ritonavirIllness visitsParasite carriageMalaria treatmentClinical studiesSmear microscopyLower riskMalaria incidenceFurther evaluationMalaria parasitesHIVMonthsScreening for Glucose-6-Phosphate Dehydrogenase Deficiency Using Three Detection Methods: A Cross-Sectional Survey in Southwestern Uganda.
Roh ME, Oyet C, Orikiriza P, Wade M, Mwanga-Amumpaire J, Boum Y, Kiwanuka GN, Parikh S. Screening for Glucose-6-Phosphate Dehydrogenase Deficiency Using Three Detection Methods: A Cross-Sectional Survey in Southwestern Uganda. American Journal Of Tropical Medicine And Hygiene 2016, 95: 1094-1099. PMID: 27672207, PMCID: PMC5094223, DOI: 10.4269/ajtmh.16-0552.Peer-Reviewed Original ResearchMeSH KeywordsChild, PreschoolCross-Sectional StudiesDiagnostic Tests, RoutineFemaleGene FrequencyGlucosephosphate DehydrogenaseGlucosephosphate Dehydrogenase DeficiencyHumansInfantMalariaMalaria, FalciparumMalaria, VivaxMalePoint-of-Care SystemsPrevalencePrimaquineRural PopulationSensitivity and SpecificityUgandaUrban PopulationConceptsG6PDd prevalenceGlucose-6-phosphate dehydrogenase deficiencyDehydrogenase deficiencySingle-dose primaquinePlasmodium falciparum transmissionSouthwestern UgandaPlasmodium ovale infectionNegative predictive valueMonths of ageCross-sectional surveyViable screening testOvale infectionsDiagnostic modalitiesStandard quantitative assayLow prevalenceRadical curePlasmodium vivaxPredictive valueSectional surveyCare testScreening testPrevalenceSevere deficiencyPrimaquineEnzyme activityPopulation Pharmacokinetics and Pharmacodynamics of Lumefantrine in Young Ugandan Children Treated With Artemether-Lumefantrine for Uncomplicated Malaria
Tchaparian E, Sambol NC, Arinaitwe E, McCormack SA, Bigira V, Wanzira H, Muhindo M, Creek DJ, Sukumar N, Blessborn D, Tappero JW, Kakuru A, Bergqvist Y, Aweeka FT, Parikh S. Population Pharmacokinetics and Pharmacodynamics of Lumefantrine in Young Ugandan Children Treated With Artemether-Lumefantrine for Uncomplicated Malaria. The Journal Of Infectious Diseases 2016, 214: 1243-1251. PMID: 27471317, PMCID: PMC5034953, DOI: 10.1093/infdis/jiw338.Peer-Reviewed Original ResearchConceptsArtemether-lumefantrineRecurrent parasitemiaLumefantrine exposurePopulation pharmacokineticsUgandan childrenYoung Ugandan childrenPlasmodium falciparum malariaDay 7 concentrationsAge 6 monthsFirst-order absorptionWhole blood concentrationsYoung childrenUncomplicated malariaFalciparum malariaBlood concentrationsTreatment outcomesLumefantrine concentrationsSignificant positive correlationParasitemiaOlder childrenPharmacokineticsLumefantrineMalariaExposure levelsOpen modelRethinking Dosing Regimen Selection of Piperaquine for Malaria Chemoprevention: A Simulation Study
Sambol NC, Tappero JW, Arinaitwe E, Parikh S. Rethinking Dosing Regimen Selection of Piperaquine for Malaria Chemoprevention: A Simulation Study. PLOS ONE 2016, 11: e0154623. PMID: 27182702, PMCID: PMC4868321, DOI: 10.1371/journal.pone.0154623.Peer-Reviewed Original ResearchMeSH KeywordsAntimalarialsChemopreventionComputer SimulationDrug Therapy, CombinationHumansMalariaMalaria, FalciparumModels, TheoreticalQuinolinesConceptsPopulation pharmacokinetic modelWeekly dosingUncomplicated Plasmodium falciparum malariaSteady-state trough concentrationsPharmacokinetic modelYoung childrenStandard therapeutic dosesYoung Ugandan childrenFirst-line therapyPlasmodium falciparum malariaFuture trial designPeak concentrationPlasma concentration-time profilesPercent of childrenConcentration-time profilesPiperaquine concentrationsMalaria chemopreventionBreakthrough infectionsMonthly administrationTrough concentrationsAcute treatmentFalciparum malariaLoading doseChemopreventive regimensInitial dosingAntiretroviral 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
Artemether-Lumefantrine Pharmacokinetics and Clinical Response Are Minimally Altered in Pregnant Ugandan Women Treated for Uncomplicated Falciparum Malaria
Nyunt MM, Nguyen VK, Kajubi R, Huang L, Ssebuliba J, Kiconco S, Mwima MW, Achan J, Aweeka F, Parikh S, Mwebaza N. Artemether-Lumefantrine Pharmacokinetics and Clinical Response Are Minimally Altered in Pregnant Ugandan Women Treated for Uncomplicated Falciparum Malaria. Antimicrobial Agents And Chemotherapy 2015, 60: 1274-1282. PMID: 26666942, PMCID: PMC4775973, DOI: 10.1128/aac.01605-15.Peer-Reviewed Original ResearchConceptsNonpregnant adultsPregnant womenArtemether-lumefantrineFalciparum malariaUncomplicated Plasmodium falciparum malariaPharmacokinetics of artemetherPregnant Ugandan womenSix-dose regimenFirst-line regimenUncomplicated falciparum malariaPlasmodium falciparum malariaHigh transmission settingsUncomplicated malariaClinical responsePharmacokinetic exposureTerminal eliminationClinical outcomesThird trimesterTreatment responseAntimalarial efficacyProphylactic periodUgandan womenPharmacokineticsDrug resistanceOverall pharmacokinetics
2013
Biochemical and immunological mechanisms by which sickle cell trait protects against malaria
Gong L, Parikh S, Rosenthal PJ, Greenhouse B. Biochemical and immunological mechanisms by which sickle cell trait protects against malaria. Malaria Journal 2013, 12: 317. PMID: 24025776, PMCID: PMC3847285, DOI: 10.1186/1475-2875-12-317.Peer-Reviewed Original ResearchConceptsSickle cell traitCell traitImmune-mediated mechanismsHost immune systemFalciparum malariaImmunological mechanismsProtective effectHO-1Immune componentsMultiple complex mechanismsImmune systemMalariaObserved protectionGenetic polymorphismsHost-parasite relationshipMicro RNAsNovel mechanismRelevant mechanismsDiseaseComplex mechanismsParasitic growth
2012
Population Pharmacokinetics and Pharmacodynamics of Piperaquine in Children With Uncomplicated Falciparum Malaria
Tarning J, Zongo I, Somé FA, Rouamba N, Parikh S, Rosenthal PJ, Hanpithakpong W, Jongrak N, Day NP, White NJ, Nosten F, Ouedraogo J, Lindegardh N. Population Pharmacokinetics and Pharmacodynamics of Piperaquine in Children With Uncomplicated Falciparum Malaria. Clinical Pharmacology & Therapeutics 2012, 91: 497-505. PMID: 22258469, PMCID: PMC3736305, DOI: 10.1038/clpt.2011.254.Peer-Reviewed Original ResearchMeSH KeywordsArtemisininsBody WeightBurkina FasoChildChild, PreschoolDrug Therapy, CombinationFemaleHumansMalaria, FalciparumMaleQuinolinesConceptsUncomplicated falciparum malariaFalciparum malariaPopulation pharmacokineticsThree-compartment distribution modelNonlinear mixed-effects modelingRecurrent malaria infectionsTotal piperaquine exposureArtemisinin combination treatmentWeight-normalized dosePlasma concentration-time profilesYoung childrenMixed-effects modelingConcentration-time profilesPiperaquine concentrationsPiperaquine exposureDose regimenMalaria infectionPlasma concentrationsPharmacodynamic propertiesCombination treatmentBody weightPiperaquineSignificant covariatesOlder childrenMalaria
2009
Intermittent Preventive Therapy for Malaria in Pregnancy: Is Sulfadoxine–Pyrimethamine the Right Drug?
Parikh S, Rosenthal PJ. Intermittent Preventive Therapy for Malaria in Pregnancy: Is Sulfadoxine–Pyrimethamine the Right Drug? Clinical Pharmacology & Therapeutics 2009, 87: 160-162. PMID: 20107451, DOI: 10.1038/clpt.2009.284.Peer-Reviewed Original Research
2007
Amodiaquine Metabolism is Impaired by Common Polymorphisms in CYP2C8: Implications for Malaria Treatment in Africa
Parikh S, Ouedraogo J, Goldstein JA, Rosenthal PJ, Kroetz DL. Amodiaquine Metabolism is Impaired by Common Polymorphisms in CYP2C8: Implications for Malaria Treatment in Africa. Clinical Pharmacology & Therapeutics 2007, 82: 197-203. PMID: 17361129, DOI: 10.1038/sj.clpt.6100122.Peer-Reviewed Original ResearchMeSH KeywordsAlkynesAmodiaquineAntimalarialsAryl Hydrocarbon HydroxylasesBenzoxazinesBurkina FasoChromatography, High Pressure LiquidCyclopropanesCytochrome P-450 CYP2C8Dose-Response Relationship, DrugDrug InteractionsEnzyme InhibitorsGenotypeHIV Protease InhibitorsHumansLopinavirMalaria, FalciparumModels, BiologicalPolymorphism, GeneticPyridinesPyrimidinonesPyronesReverse Transcriptase InhibitorsSaquinavirSpectrophotometry, UltravioletSulfonamidesTreatment OutcomeTrimethoprimConceptsAntimalarial drug amodiaquineMalaria-infected patientsAntiretroviral drug efavirenzImportant clinical implicationsAmodiaquine metabolismCYP2C8 genotypeMalaria treatmentN-desethylamodiaquineCYP2C8 variantsCYP2C8 activityCYP2C8 inhibitorsDrug interactionsDefective metabolismClinical implicationsCYP2C8Common polymorphismsDrug efavirenzMetabolismRelevant concentrationsDrugsEfficacyPrimary metabolitesAllele frequenciesToxicitySample size