Trial reportClinical pharmacology and therapeutics2021
Pharmacokinetics and Drug-Drug Interactions of Isoniazid and Efavirenz in Pregnant Women Living With HIV in High TB Incidence Settings: Importance of Genotyping.
Open access · hybridAbstract readMulticenter StudyRandomized Controlled Trial
In one paragraph
Trial report in Clinical pharmacology and therapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 2 pooled it
0.5field-weighted citation impact, top 21% of its field
What it found
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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.
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Who cites it
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 34 citations in OpenAlex.
- The Pharmacokinetics and Target Attainment of Antimicrobial Drugs Throughout Pregnancy: Part III Non-penicillin and Non-cephalosporin Drugs.Clinical pharmacokinetics · 2023Pooled it
- Influence of N-acetyltransferase 2 (NAT2) genotype/single nucleotide polymorphisms on clearance of isoniazid in tuberculosis patients: a systematic review of population pharmacokinetic models.European journal of clinical pharmacology · 2022Pooled it
- Hepatotoxicity Among People With HIV and Receiving Isoniazid Preventive Therapy in Pregnancy and Postpartum: The Role of Antiretroviral Regimen and Pharmacogenetics.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026Trial
- Population pharmacokinetics of pyrazinamide and isoniazid in plasma and cerebrospinal fluid from South African adults with tuberculous meningitis.Antimicrobial agents and chemotherapy · 2025Trial
- High-Dose Isoniazid Lacks EARLY Bactericidal Activity against Isoniazid-resistant Tuberculosis Mediated by katG Mutations: A Randomized Phase II Clinical Trial.American journal of respiratory and critical care medicine · 2024Trial
- Prevalence of neurotoxicity symptoms among postpartum women on isoniazid preventive therapy and efavirenz-based treatment for HIV: an exploratory objective of the IMPAACT P1078 randomized trial.BMC pregnancy and childbirth · 2023Trial
- Pharmacokinetics and Safety of 3 Months of Weekly Rifapentine and Isoniazid for Tuberculosis Prevention in Pregnant Women.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Trial
- Factors Influencing Phenoconversion in CYP-Mediated Drug Metabolism: A Scoping Review.Pharmacy (Basel, Switzerland) · 2026Review
- Tuberculosis Prevention in Pregnant Women Living with HIV: A Review of the Current Management Strategies and Guidance.Infection and drug resistance · 2026Review
- Pharmacokinetics of first-line tuberculosis drugs rifampin, isoniazid, ethambutol, and pyrazinamide during pregnancy and postpartum with and without efavirenz-based antiretroviral treatment: IMPAACT P1026s study.Antimicrobial agents and chemotherapy · 2025Article
- Pharmacokinetic Adaptations in Pregnancy: Implications for Optimizing Antiretroviral Therapy in HIV-Positive Women.Pharmaceutics · 2025Review
- An Update on the Clinical Management of HIV and Tuberculosis Co-Infection in Pregnancy: TB Preventative Therapy, Long-Acting ARVs, and Bedaquiline-Based Regimens.Current HIV/AIDS reports · 2025Review
- Mechanisms of altered hepatic drug disposition during pregnancy: small molecules.Expert opinion on drug metabolism & toxicology · 2025Review
- Pharmacokinetics, pharmacogenetics, and toxicity of co-administered efavirenz and isoniazid.Southern African journal of HIV medicine · 2025Article
- Pharmacogenetics in Tuberculosis-HIV Coinfected Populations: A Systematic Review of Genetic Variants Influencing Antiretroviral and Anti-Tuberculosis Drug Response.Journal of multidisciplinary healthcare · 2025Review
- The impact of alcohol and illicit substance use on the pharmacokinetics of first-line TB drugs.The Journal of antimicrobial chemotherapy · 2024Article
- Assessing potential drug-drug interactions between clofazimine and other frequently used agents to treat drug-resistant tuberculosis.Antimicrobial agents and chemotherapy · 2024Article
- Evaluating pediatric tuberculosis dosing guidelines: A model-based individual data pooled analysis.PLoS medicine · 2023Article
- Application of a physiologically based pharmacokinetic model to predict isoniazid disposition during pregnancy.Clinical and translational science · 2023Article
- Pharmacogenetics as part of recommended precision medicine for tuberculosis treatment in African populations: Could it be a reality?Clinical and translational science · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
39 authors at 20 institutions in 9 countries.
Kamunkhwala GausiDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.ORCID 0000-0002-9002-8087
Lubbe WiesnerDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Jennifer NormanDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Carole L WallisBARC Laboratories South Africa, Johannesburg, South Africa.
Carolyne Onyango-MakumbiMakerere University - Johns Hopkins University Research Collaboration, Kampala, Uganda.
Tsungai ChipatoDepartment of Obstetrics and Gynaecology, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe.
David W HaasDepartments of Medicine, Pharmacology, Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Renee BrowningDivision of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Nahida ChakhtouraNational Institutes of Health (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, Maryland, USA.
Grace MontepiedraCenter for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.
Lisa AaronCenter for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.
Katie McCarthyFHI 360, Durham, North Carolina, USA.
Sarah BradfordFHI 360, Durham, North Carolina, USA.
Tichaona VhemboDepartment of Obstetrics and Gynaecology, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe.
Lynda Stranix-ChibandaDepartment of Obstetrics and Gynaecology, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe.
Gaerolwe R MashetoBotswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
Avy ViolariThe Perinatal HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa.
Blandina T MmbagaKilimanjaro Christian Medical Centre, Moshi, Tanzania.
Linda AurpibulResearch Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand.
Ramesh BhosaleByramjee Jeejeebhoy Government Medical College, Pune, India.
Neetal NevrekharByramjee Jeejeebhoy Government College-Johns Hopkins Clinical Research Site, Pune, India.
Vanessa RouzierWeill Cornell Center for Global Health New York, New York, New York, USA.
Enid KabughoMU-JHU Research Collaboration, Kampala, Uganda.
Mercy MutambanengweUniversity of Zimbabwe College of Health Sciences Clinical Trials Research Centre, Harare, Zimbabwe.
Vongai ChanaiwaUniversity of Zimbabwe College of Health Sciences Clinical Trials Research Centre, Harare, Zimbabwe.
Mandisa NyatiPerinatal HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa.
Tsungai MhembereUniversity of Zimbabwe College of Health Sciences Clinical Trials Research Centre, Harare, Zimbabwe.
Fuanglada TongprasertDepartment of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Anneke HesselingDepartment of Paediatrics and Child Health, The Desmond Tutu TB Center, Stellenbosch University, Tygerberg, South Africa.
Katherine ShinDivision of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Bonnie ZimmerUniversity of California, Los Angeles, California, USA.
Diane CostelloFrontier Science Foundation, Amherst, New York, USA.
Patrick Jean-PhilippeDivision of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Timothy R SterlingVanderbilt Tuberculosis Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Gerhard TheronDepartment of Obstetrics and Gynaecology, Stellenbosch University, Cape Town, South Africa.
Adriana WeinbergUniversity of Colorado Denver Anschutz Medical Campus, Aurora, Colorado, USA.
Amita GuptaJohns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Paolo DentiDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
IMPAACT P1078 (TB APPRISE) Study Group TeamResearch Group: IMPAACT P1078 Study Group Team, Durham, North Carolina, USA.
University of Zimbabwe · ZWNational Institutes of Health · USUniversity of Cape Town · ZACancer Research And Biostatistics · USChiang Mai University · THFamily Health International 360 · USMUJHU Research Collaboration · UGUniversity of the Witwatersrand · ZABotswana Harvard AIDS Institute Partnership · BWCornell University · USDesmond Tutu HIV Foundation · ZAFrontier Science & Technology Research Foundation · USGovernment Medical College · INJohns Hopkins University · USKilimanjaro Christian Medical Centre · TZLancet Laboratories · ZAMaterials Research Group (United States) · USMeharry Medical College · USStellenbosch University · ZAUniversity of California, Los Angeles · US
Funding
Leadership and Operations Center (LOC), AIDS Clinical Trials Group (ACTG); LOC 1/UM1AI068636 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, RAJESH T GANDHI · 2011 to 2026
$1073.1MLOC-IMPAACT Leadership GroupPharmacokinetics and Safety of Remdesivir for Treatment of COVID-19 in Pregnant Women in the USUM1AI068632 · NIAID · SOCIAL AND SCIENTIFIC SYSTEMS, INC. · PI Jennifer Jao, Sharon A Nachman · 2011 to 2026
$278.1MStatistical and Data Management Center (SDMC), AIDS Clinical Trials Group (ACTG)UM1AI068634 · NIAID · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Marlene Ann Cooper, Michael David Hughes · 2011 to 2026
$246.6MStatistical and Data Management Center-Pediatric,Adolescent, and Maternal CTGUM1AI068616 · NIAID · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Sean Scott Brummel, Marlene Ann Cooper · 2011 to 2026
$155.6MValidation, CLIA and Qualification (VQC): Enhancing the RS ratio as a tool for AIDS Clinical Trial Group (ACTG) tuberculosis trialsUM1AI106701 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Grace M Aldrovandi · 2014 to 2026
$116.8MInternational Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) GroupU01AI068632 · NIAID · SOCIAL AND SCIENTIFIC SYSTEMS, INC. · PI JACKSON, J BROOKS · 2006 to 2010
$109.7MUZ-UCSF CTUUM1AI069436 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ZVAVAHERA MIKE CHIRENJE, LYNDA STRANIX-CHIBANDA · 2012 to 2026
$75.9MUZ-UCSF Clinical Trials UnitU01AI069436 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHIRENJE, ZVAVAHERA MIKE · 2007 to 2011
$49.3MLC - IMPAACT Leadership GroupUM1AI106716 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Grace M Aldrovandi · 2014 to 2026
$47.2MThe Johns Hopkins University - Uganda Clinical Trials UnitUM1AI069530 · NIAID · JOHNS HOPKINS UNIVERSITY · PI MARY Glenn Fowler, Philippa Musoke · 2012 to 2026
$34.8MThe Johns Hopkins Baltimore-Washington-India Clinical Trials Unit (BWI CTU)UM1AI069465 · NIAID · JOHNS HOPKINS UNIVERSITY · PI Charles W. Flexner, Amita Gupta · 2012 to 2026
$34.1MThailand HIV/AIDS and Infectious Disease Clinical Trials Unit (THAI CTU)UM1AI069399 · NIAID · CHIANG MAI UNIVERSITY · PI Kiat Ruxrungtham, Khuanchai Supparatpinyo · 2012 to 2026
$25.0MNIAID NIH HHS R01 AI077505NIAID NIH HHS U01 AI068632NIAID NIH HHS U01 AI069436NIAID NIH HHS UM1 AI068616NIAID NIH HHS UM1 AI068632NIAID NIH HHS UM1 AI068634NIAID NIH HHS UM1 AI068636NIAID NIH HHS UM1 AI069399NIAID NIH HHS UM1 AI069436NIAID NIH HHS UM1 AI069465NIAID NIH HHS UM1 AI069521NIAID NIH HHS UM1 AI069530NIAID NIH HHS UM1 AI106701NIAID NIH HHS UM1 AI106716NICHD NIH HHS HHSN275201800001CNICHD NIH HHS HHSN275201800001INIMH NIH HHS R21 MH083308
Abstract
The World Health Organization guidelines recommend that individuals living with HIV receive ≥ 6 months of isoniazid preventive therapy, including pregnant women. Yet, plasma isoniazid exposure during pregnancy, in the antiretroviral therapy era, has not been well-described. We investigated pregnancy-induced and pharmacogenetic-associated pharmacokinetic changes and drug-drug interactions between isoniazid and efavirenz in pregnant women. Eight hundred forty-seven women received isoniazid for 28 weeks, either during pregnancy or at 12 weeks postpartum, and 786 women received efavirenz. After adjusting for NAT2 and CYP2B6 genotype and weight, pregnancy increased isoniazid and efavirenz clearance by 26% and 15%, respectively. Isoniazid decreased efavirenz clearance by 7% in CYP2B6 normal metabolizers and 13% in slow and intermediate metabolizers. Overall, both isoniazid and efavirenz exposures were reduced during pregnancy, but the main determinants of drug concentration were NAT2 and CYP2B6 genotypes, which resulted in a five-fold difference for both drugs between rapid and slow metabolizers.
Indexed as
AdolescentAdultAlkynesAnti-HIV AgentsAntitubercular AgentsArylamine N-AcetyltransferaseBenzoxazinesBody WeightCyclopropanesCytochrome P-450 CYP2B6Double-Blind MethodDrug InteractionsEquivalence Trials as TopicFemaleGenotypeHIV InfectionsAlkynesAnti-HIV AgentsAntitubercular AgentsArylamine N-AcetyltransferaseBenzoxazinesCyclopropanesCytochrome P-450 CYP2B6efavirenzIsoniazidNAT2 protein, humanReverse Transcriptase Inhibitors
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