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Farmakokinetiske egenskaber af antiretrovirale og anti-tuberkuloselægemidler under graviditet og postpartum

3. august 2026 opdateret af: National Institute of Allergy and Infectious Diseases (NIAID)
Formålet med denne undersøgelse er at evaluere de farmakokinetiske (PK) egenskaber af antiretrovirale (ARV) og anti-tuberkulose (TB) lægemidler administreret under graviditet og postpartum.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

Denne undersøgelse vil evaluere de farmakokinetiske (PK) egenskaber af antiretrovirale (ARV) og anti-tuberkulose (TB) lægemidler administreret under graviditet og postpartum.

IMPAACT 2026 er et klinisk fase IV observationsstudie. Deltagerne tildeles ikke de lægemidler, der undersøges, men modtager allerede lægemidlerne til klinisk pleje efter ordination af deres kliniske plejeudbydere. De er tilmeldt undersøgelsesarme i henhold til de lægemidler, de modtager gennem klinisk behandling, og hvis de er på flere lægemidler af interesse, er de i stand til at tilmelde sig flere arme samtidigt. Ingen ARV'er eller TB-behandlingsmidler leveres som en del af denne undersøgelse. Alle lægemidler, der undersøges, leveres af ikke-undersøgelseskilder. Studiesponsoren føjede denne observationsundersøgelse til et eksisterende undersøgelsesnummer for nyt lægemiddel (IND) til off-label brug i tilfælde af, at deltagerens kliniske plejeudbyder beslutter at ordinere en højere dosis end den godkendte dosis, hvis PK-resultaterne for den godkendte dosis indikerer, at lægemidlet eksponering kan være utilstrækkelig.

Denne undersøgelse består af fem komponenter, som igen består af arme, der er specifikke for hvert lægemiddel eller lægemiddelkombination, der evalueres:

  • Komponent 1 (Arms 1.1, 1.2. 1.3. 1.4. og 1.5): Gravide kvinder, der lever med HIV (WLHIV), der modtager orale ARV'er og ingen TB-lægemidler, og deres spædbørn.
  • Komponent 2 (arm 2.1): Gravide WLHIV og HIV-uinficerede kvinder, som fik langtidsvirkende/forlænget frigivelse ARV'er under graviditeten, og deres spædbørn.
  • Komponent 3 (arme 3.1, 3.2 og 3.3): Gravid WLHIV, der modtager ARV'er og førstelinje-TB-behandling, og deres spædbørn.
  • Komponent 4 (arm 4.1): Gravide WLHIV og HIV-ikke-inficerede kvinder, der modtager andenlinje-TB-behandling, og deres spædbørn.
  • Komponent 5 (Arms 5.1, 5.2. og 5.3): Postpartum WLHIV amning, mens de modtager orale ARV'er, og deres spædbørn.

Hver arm vil åbne for optjening uafhængigt og vil optjene uafhængigt over cirka 36 måneder fra den første tilmelding i hver arm.

Deltagere i komponent 1 vil blive fulgt op til 12 uger efter fødslen for mødre og op til 24 uger efter fødslen for spædbørn. Deltagere i komponent 2 vil blive fulgt op til 5 uger efter fødslen for mødre og spædbørn. Deltagere i komponent 3, 4 og 5 vil blive fulgt op til 24 uger efter fødslen for mødre og spædbørn.

Studiebesøg kan omfatte:

  • Komponent 1: Maternelle kliniske og laboratorieevalueringer og PK-prøvetagning i andet trimester (2T), tredje trimester (3T), fødslen og 6-12 uger efter fødslen (PP). Spædbørns kliniske evalueringer og udvaskning af PK-prøver ved fødslen og 5-9 dage efter fødslen.
  • Komponent 2: Maternelle kliniske og laboratoriemæssige evalueringer og PK-prøveudtagning ved fødslen. Spædbørns kliniske evalueringer og udvaskning af farmakokinetiske prøver ved fødslen, 5-9 dage og 12-16 dage efter fødslen. Moder- og spædbarnsmodermælk overfører PK-prøver 5-9 dage, 12-16 dage og 3-5 uger efter fødslen.
  • Komponent 3: Maternelle kliniske og laboratoriemæssige evalueringer og PK prøveudtagning i andet trimester (2T), tredje trimester (3T), fødslen og 2-8 uger efter fødslen (PP). Spædbørns kliniske evalueringer og udvaskning af PK-prøver ved fødslen og 5-9 dage efter fødslen. Moder- og spædbarnsmodermælk overfører PK-prøver 5-9 dage, 2-8 uger og 16-24 uger efter fødslen.
  • Komponent 4: Maternelle kliniske og laboratorieevalueringer og PK-prøvetagning i andet trimester (2T), tredje trimester (3T), fødslen og 2-8 uger efter fødslen (PP). Spædbørns kliniske evalueringer og udvaskning af PK-prøver ved fødslen og 5-9 dage efter fødslen. Moder- og spædbarnsmodermælk overfører PK-prøver 5-9 dage, 2-8 uger og 16-24 uger efter fødslen.
  • Komponent 5: Kliniske evalueringer af mødre og spædbørn og PK-prøveudtagning af modermælk 5-9 dage, 2-12 uger og 16-24 uger efter fødslen.

Undersøgelsestype

Observationel

Tilmelding (Faktiske)

205

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Brasilien
      • Rio de Janeiro, Brasilien, 20221-903
        • Hospital Federal dos Servidores do Estado NICHD CRS
      • Rio de Janeiro, Brasilien, 26030
        • Hosp. Geral De Nova Igaucu Brazil NICHD CRS
  • Forenede Stater
    • California
      • Los Angeles, California, Forenede Stater, 90033
        • Usc La Nichd Crs
      • Los Angeles, California, Forenede Stater, 90095-1752
        • David Geffen School of Medicine at UCLA NICHD CRS
      • San Diego, California, Forenede Stater, 92103
        • University of California, UC San Diego CRS- Mother-Child-Adolescent HIV Program
    • Colorado
      • Aurora, Colorado, Forenede Stater, 80045
        • Univ. of Colorado Denver NICHD CRS
    • Florida
      • Fort Lauderdale, Florida, Forenede Stater, 33316
        • South Florida CDTC Ft Lauderdale NICHD CRS
      • Jacksonville, Florida, Forenede Stater, 32209
        • University of Florida Jacksonville NICHD CRS
      • Miami, Florida, Forenede Stater, 33136
        • Pediatric Perinatal HIV NICHD CRS
    • Georgia
      • Atlanta, Georgia, Forenede Stater, 30322
        • Emory University School of Medicine NICHD CRS
    • Illinois
      • Chicago, Illinois, Forenede Stater, 60612
        • Rush University Cook County Hospital Chicago NICHD CRS
      • Chicago, Illinois, Forenede Stater, 60614
        • Lurie Children's Hospital of Chicago (LCH) CRS (Site ID: 4001)
    • Maryland
      • Baltimore, Maryland, Forenede Stater, 21287
        • Johns Hopkins Univ. Baltimore NICHD CRS
    • New York
      • The Bronx, New York, Forenede Stater, 10457
        • Bronx-Lebanon Hospital Center NICHD CRS
      • The Bronx, New York, Forenede Stater, 10461
        • Jacobi Med. Ctr. Bronx NICHD CRS
  • Indien
    • Maharashtra
      • Pune, Maharashtra, Indien, 411001
        • Byramjee Jeejeebhoy Medical College (BJMC) CRS
  • Kenya
      • Kericho, Kenya, 20200
        • Kenya Medical Research Institute / Walter Reed Project Clinical Research Center, Kericho CRS
  • Puerto Rico
      • San Juan, Puerto Rico, 00935
        • IMPAACT/ Gamma Project/ UPR Pediatric HIV/AIDS Research CRS
  • Sydafrika
      • Cape Town, Sydafrika, 7505
        • Desmond Tutu TB Centre - Stellenbosch University (DTTC-SU) CRS
      • Tygerberg Hills, Sydafrika, 7505
        • Famcru Crs
    • Gauteng
      • Johannesburg, Gauteng, Sydafrika, 2001
        • Wits RHI Shandukani Research
  • Thailand
    • Bangkoknoi
      • Bangkok, Bangkoknoi, Thailand, 10700
        • Siriraj Hospital, Mahidol University NICHD CRS
  • Uganda
      • Kampala, Uganda
        • Baylor-Uganda CRS

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

  • Barn
  • Voksen
  • Ældre voksen

Tager imod sunde frivillige

Ingen

Prøveudtagningsmetode

Ikke-sandsynlighedsprøve

Studiebefolkning

Gravide og postpartum kvinder, der lever med og uden HIV (WLHIV og HIV-ikke-inficerede kvinder), der modtager ARV- og/eller TB-lægemidler under undersøgelse, og deres spædbørn.

Beskrivelse

Inklusionskriterier:

Komponent 1: Gravid WLHIV, der modtager orale ARV'er og ingen TB-lægemidler, og deres spædbørn

  • Moderen er myndig eller på anden måde i stand til at give uafhængigt informeret samtykke som bestemt af webstedets standarddriftsprocedurer (SOP'er) og i overensstemmelse med politikker og procedurer for webstedets institutionelle revisionsudvalg (IRB)/etisk komité (EC) og er villig og i stand til at give skriftligt informeret samtykke til hendes egen og hendes spædbarns deltagelse i denne undersøgelse.
  • Før studiestart blev HIV-status bekræftet som HIV-inficeret i henhold til undersøgelsesprotokol.

  • Ved studiestart, gravid og i et af følgende to tilmeldingsvinduer baseret på det bedste tilgængelige obstetriske estimat af gestationsalder:

    • Andet trimester: gestationsalder på 20 0/7 til 26 6/7 uger
    • Tredje trimester: gestationsalder på 30 0/7 til 37 6/7 uger

  • Ved studiestart, modtagelse af mindst én af følgende orale ARV-lægemidler eller lægemiddelkombinationer baseret på moderens rapport og tilgængelige lægejournaler:

    • Arm 1.1: Bictegravir (BIC) 50 mg q.d.
    • Arm 1.2: Doravirin (DOR) 100 mg q.d.
    • Arm 1.3: Tenofoviralafenamid (TAF) - 10 mg q.d. boostet med cobicistat
    • Arm 1.4: TAF 25 mg q.d. uden at booste
    • Arm 1.5: TAF 25 mg q.d. boostet med cobicistat eller ritonavir
  • Ved studiestart, planlægning at fortsætte den nuværende ARV-kur gennem mindst 12 uger efter fødslen, baseret på moderens rapport og tilgængelige lægejournaler.
  • Har ved studiestart modtaget lægemidlet eller lægemiddelkombinationen under undersøgelse i den påkrævede dosis i mindst to uger, baseret på moderens rapport og tilgængelige lægejournaler.
  • Ved undersøgelsens start, vurderet af undersøgelsespersonalet at have ingen identificerede barrierer for at afslutte indledende PK-prøvetagning inden for 20 0/7 - 26 6/7 ugers graviditet (andet trimester) eller 30 0/7 til 37 6/7 ugers svangerskab (tredje trimester) og inden for 14 dage efter tilmelding.
  • Hvis du modtager en generisk formulering af lægemidlet eller lægemiddelkombinationen under undersøgelse, godkendelse af formuleringen ved forsøgsprotokol.
  • Ved studiestart, ikke at modtage nogen TB-lægemidler (til enten profylakse eller behandling), baseret på moderrapport og tilgængelige lægejournaler.

Komponent 2: Gravide WLHIV og HIV-ikke-inficerede kvinder, som fik langtidsvirkende/forlænget frigivelse ARV'er under graviditeten, og deres spædbørn

  • Hvis myndig eller på anden måde er i stand til at give uafhængigt informeret samtykke som bestemt af webstedets SOP'er og i overensstemmelse med webstedets IRB/EC-politikker og -procedurer: Villig og i stand til at give skriftligt informeret samtykke til hendes egen og hendes spædbarns deltagelse i denne undersøgelse.
  • Hvis ikke myndig eller på anden måde er ude af stand til at give uafhængigt informeret samtykke som bestemt af webstedets SOP'er og i overensstemmelse med webstedets IRB/EC-politikker og -procedurer: Forælder/værge eller anden juridisk autoriseret repræsentant for moderen og hendes spædbarn er villig og i stand til at give skriftlige oplysninger informeret samtykke til moderen og hendes spædbarns deltagelse i undersøgelsen; desuden er moderen, når det er relevant, villig og i stand til at give skriftligt samtykke til sin egen og sit spædbarns studiedeltagelse.
  • Påtænker ved studiestart at levere på den studietilknyttede klinik eller hospital, baseret på moderrapport.
  • Ved studiestart, gestationsalder på mindst 24 0/7 uger baseret på bedste tilgængelige obstetriske estimat af gestationsalder, og endnu ikke født.

  • Har ved studiestart modtaget mindst én administration af følgende, baseret på tilgængelige lægejournaler, under den aktuelle graviditet:

    • Arm 2.1: Langtidsvirkende injicerbar formulering af cabotegravir (CAB LA) (enhver dosis)

Komponent 3: Gravid WLHIV, der modtager ARV'er med førstelinjes TB-behandling, og deres spædbørn

  • Moderen er myndig eller på anden måde i stand til at give uafhængigt informeret samtykke som bestemt af webstedets SOP'er og i overensstemmelse med webstedets IRB/EC-politikker og -procedurer, og er villig og i stand til at give skriftligt informeret samtykke til sin egen og sit spædbarns deltagelse i denne undersøgelse.
  • Før studiestart blev HIV-status bekræftet som HIV-inficeret i henhold til undersøgelsesprotokol.

  • Ved studiestart, gravid og i et af følgende to tilmeldingsvinduer, baseret på det bedste tilgængelige obstetriske estimat af gestationsalder:

    • Andet trimester: gestationsalder på 20 0/7 til 26 6/7 uger
    • Tredje trimester: gestationsalder på 30 0/7 til 37 6/7 uger

  • Ved studiestart, modtagelse af mindst to af følgende førstelinje-TB-behandlingslægemidler under undersøgelse OG mindst én af følgende ARV-lægemidler eller lægemiddelkombinationer, der undersøges, baseret på moderens rapport og tilgængelige lægejournaler:

    • Første-line TB-behandlingsmidler:
    • Isoniazid (INH) 4-6 mg/kg (maks. 300 mg) q.d.
    • Rifampin (RIF) 8-12 mg/kg (max 600 mg) q.d.
    • Rifabutin (RFB) 150-300 mg q.d.
    • Ethambutol (EMB) 15-20 mg/kg q.d.
    • Pyrazinamid (PZA) 20-30 mg/kg q.d.
    • Moxifloxacin (MFX) 400 mg eller 800 mg q.d
    • ARV'er:
    • Arm 3.1: Dolutegravir (DTG) 50 mg b.i.d. når det kombineres med RIF eller 50 mg q.d. hvis RIF ikke er en del af TB-kuren
    • Arm 3.2: Atazanavir/ritonavir (ATV/r) ≥300/100 mg q.d. eller Darunavir/ritonavir (DRV/r) ≥ 600/100 mg b.i.d.
    • Arm 3.3: Lopinavir/ritonavir (LPV/r) 800/200 mg b.i.d.
  • Har ved studiestart modtaget lægemiddelkombinationen under undersøgelse i den påkrævede dosis i mindst to uger baseret på moderens rapport og tilgængelige lægejournaler.
  • Ved undersøgelsens start, vurderet af undersøgelsespersonalet at have ingen identificerede barrierer for at afslutte indledende PK-prøvetagning inden for 20 0/7 - 26 6/7 ugers graviditet (andet trimester) eller 30 0/7 til 37 6/7 ugers svangerskab (tredje trimester) og inden for 14 dage efter tilmelding.
  • Hvis du modtager en generisk ARV- eller TB-formulering af det undersøgte lægemiddel eller lægemiddelkombination ved indtræden i undersøgelsen, godkendelse af formuleringen pr. undersøgelsesprotokol.
  • Ved studiestart, planlægger at fortsætte den nuværende ARV-kur gennem mindst 8 uger efter fødslen, baseret på moderens rapport og tilgængelige lægejournaler.

Komponent 4 Inklusionskriterier: Gravide WLHIV og HIV-ikke-inficerede kvinder, der modtager andenlinje-TB-behandling, og deres spædbørn

  • Moderen er myndig eller på anden måde i stand til at give uafhængigt informeret samtykke som bestemt af webstedets SOP'er og i overensstemmelse med webstedets IRB/EC-politikker og -procedurer, og er villig og i stand til at give skriftligt informeret samtykke til sin egen og sit spædbarns deltagelse i denne undersøgelse.
  • Før studiestart bekræftes HIV-status som HIV-inficeret eller HIV-ikke-inficeret, pr. undersøgelsesprotokol.

  • Ved studiestart, gravid og i et af følgende to tilmeldingsvinduer baseret på det bedste tilgængelige obstetriske estimat af gestationsalder:

    • Andet trimester: gestationsalder på 20 0/7 til 26 6/7 uger
    • Tredje trimester: gestationsalder på 30 0/7 til 37 6/7 uger

  • Ved studiestart, modtagelse af mindst én af følgende anden-line TB-behandlingslægemidler, der er under undersøgelse, baseret på moderens rapport og tilgængelige lægejournaler:

    • Arm 4.1: Andenlinjes TB-behandlingsmidler:
    • Levofloxacin (LFX) 750mg - 1000mg q.d.
    • Clofazimin (CFZ) 100 mg q.d.
    • Linezolid (LZD) 300mg - 600mg q.d.
    • Bedaquilin (BDQ) 200mg t.i.w.
    • Delamanid (DLM) 100mg b.i.d.
    • Moxifloxacin (MFX) 400mg eller 800mg q.d og mindst ét ​​andet anden-line TB behandlingslægemiddel under undersøgelse
  • Har ved studiestart modtaget lægemidlerne under undersøgelse i den påkrævede dosis i mindst to uger, baseret på moderens rapport og tilgængelige lægejournaler.
  • Ved undersøgelsens start, vurderet af undersøgelsespersonalet at have ingen identificerede barrierer for at afslutte indledende PK-prøvetagning inden for 20 0/7 - 26 6/7 ugers graviditet (andet trimester) eller 30 0/7 til 37 6/7 ugers svangerskab (tredje trimester) og inden for 14 dage efter tilmelding.
  • Hvis du modtager en generisk formulering af det eller de lægemidler, der undersøges, godkendelse af formuleringen pr. undersøgelsesprotokol ved indtræden i undersøgelsen.

Komponent 5: Postpartum WLHIV amning, mens du modtager orale ARV'er, og deres spædbørn

  • Moderen er myndig eller på anden måde i stand til at give uafhængigt informeret samtykke som bestemt af webstedets SOP'er og i overensstemmelse med webstedets IRB/EC-politikker og -procedurer, og er villig og i stand til at give skriftligt informeret samtykke til sin egen og sit spædbarns deltagelse i denne undersøgelse.
  • Før studiestart bekræftes HIV-status som HIV-inficeret i henhold til undersøgelsesprotokol.
  • Ved studiestart, inden for 5-9 dage efter levering (inklusive).
  • Ved start i undersøgelsen har ammende mor-spædbarn-par til hensigt at fortsætte eksklusiv amning i mindst 16 uger efter fødslen.

  • Ved indgangen til undersøgelsen modtager mor et af følgende orale ARV-lægemidler eller lægemiddelkombinationer:

    • Arm 5.1: Atazanavir/ritonavir (ATV/r)
    • Arm 5.2: Darunavir/ritonavir (DRV/r)
    • Arm 5.3: Lopinavir/ritonavir (LPV/r)
  • Ved studiestart har moderen modtaget lægemidlet eller lægemiddelkombinationerne under undersøgelse i den nødvendige dosis i mindst to uger, baseret på moderens rapport og tilgængelige lægejournaler.
  • Ved indtræden i undersøgelsen, vurderet af undersøgelsespersonalet som ingen identificerede barrierer for at fuldføre indledende PK-prøvetagning inden for 5-9 dage efter levering PK-prøvetagningsvinduet.
  • Ved studiestart planlægger mor at fortsætte den nuværende ARV-kur gennem mindst 16 uger efter fødslen, baseret på moderens rapport og tilgængelige lægejournaler.
  • Hvis du modtager en generisk ARV-formulering af det undersøgte lægemiddel eller lægemiddelkombination ved indtræden i undersøgelsen, godkendelse af formuleringen pr. undersøgelsesprotokol.
  • Ved studiestart vejer spædbarnet mindst 1000 gram, baseret på tilgængelige lægejournaler.
  • Ved start i undersøgelsen har spædbarnet ikke nogen alvorlig medfødt misdannelse eller anden medicinsk tilstand, der ikke er forenelig med livet, eller som ville forstyrre undersøgelsesdeltagelsen eller fortolkningen, som vurderet af stedets investigator.

Udelukkelseskriterier for komponenter 1-4:

  • Ved indtræden i undersøgelsen har mor modtaget inden for de seneste 14 dage medicin, der vides at interferere med absorption, metabolisme eller clearance af lægemidlet eller lægemiddelkombinationen under undersøgelse (se undersøgelsesprotokol) baseret på moderens rapport og tilgængelige lægejournaler.

    • Bemærk: RIF er tilladt for mødre i komponent 3 og 4, der evalueres for TB- og ARV-lægemiddelinteraktioner.
  • Har ved studiestart et klinisk eller laboratoriefund eller en tilstand, som efter undersøgelsesstedets vurdering sandsynligvis vil kræve en ændring af det ARV- eller TB-lægemiddel, der undersøges, i løbet af studieopfølgningsperioden.
  • Kun arm 1.3, 1.4 og 1.5: Ved studiestart har mor modtaget TDF-baseret terapi inden for de seneste 6 måneder.

Komponent 5 Eksklusionskriterier

  • Mor er i øjeblikket tilmeldt komponent 1, 2, 3 eller 4.
  • Ved indtræden i undersøgelsen har moderen eller spædbarnet inden for de seneste 14 dage modtaget medicin, der vides at interferere med absorption, metabolisme eller clearance af lægemidlet eller lægemiddelkombinationen, der undersøges, baseret på moderens rapport og tilgængelige lægejournaler (se undersøgelsesprotokol).
  • Ved optagelse i undersøgelsen har mor eller spædbarn et klinisk eller laboratoriefund eller en tilstand, som efter undersøgelsesstedets opfattelse sandsynligvis vil kræve en ændring af det undersøgte lægemiddel under undersøgelsesopfølgningen.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Observationsmodeller: Kohorte
  • Tidsperspektiver: Fremadrettet

Kohorter og interventioner

Gruppe / kohorte
Intervention / Behandling
Komponent 1: Arm 1.1: Bictegravir (BIC) 50 mg q.d.
Kvinder ≥ 20 ugers graviditet, der ikke får TB-medicin og får bictegravir (BIC) 50 mg én gang dagligt (q.d.), og deres spædbørn
Medicin: Bictegravir (BIC)
Administreret i overensstemmelse med indlægssedlerne og/eller instruktionerne fra de ikke-undersøgelseskilder, som ordinerer eller leverer lægemidlerne til deltagerne
Komponent 1: Arm 1.2: Doravirin (DOR) 100 mg q.d.
Kvinder ≥ 20 ugers svangerskab, der ikke får TB-medicin og får doravirin (DOR) 100 mg q.d., og deres spædbørn
Medicin: Doravirin (DOR)
Administreret i overensstemmelse med indlægssedlerne og/eller instruktionerne fra de ikke-undersøgelseskilder, som ordinerer eller leverer lægemidlerne til deltagerne
Komponent 1: Arm 1.4: TAF 25 mg q.d. uden at booste
Kvinder ≥ 20 ugers svangerskab, der ikke får TB-medicin og får TAF 25 mg q.d. uden at booste, og deres spædbørn
Medicin: Tenofoviralafenamid (TAF)
Administreret i overensstemmelse med indlægssedlerne og/eller instruktionerne fra de ikke-undersøgelseskilder, som ordinerer eller leverer lægemidlerne til deltagerne
Komponent 1: Arm 1.5: TAF 25 mg q.d. med boostning
Kvinder ≥ 20 ugers svangerskab, der ikke får TB-medicin og får TAF 25 mg q.d. boostet med cobicistat eller ritonavir og deres spædbørn
Medicin: Tenofoviralafenamid (TAF)
Administreret i overensstemmelse med indlægssedlerne og/eller instruktionerne fra de ikke-undersøgelseskilder, som ordinerer eller leverer lægemidlerne til deltagerne
Medicin: Cobicistat
Administreret i overensstemmelse med indlægssedlerne og/eller instruktionerne fra de ikke-undersøgelseskilder, som ordinerer eller leverer lægemidlerne til deltagerne
Medicin: Ritonavir
Administreret i overensstemmelse med indlægssedlerne og/eller instruktionerne fra de ikke-undersøgelseskilder, som ordinerer eller leverer lægemidlerne til deltagerne
Komponent 3: Arm 3.1: Dolutegravir (DTG) 50 mg
Kvinder ≥ 20 ugers svangerskab, der modtager førstelinje-TB-behandling med mindst to af følgende TB-behandlingsmidler: isoniazid (INH), rifampin (RIF), rifabutin (RFB), ethambutol (EMB), pyrazinamid (PZA), moxifloxacin (MFX) ), og får dolutegravir (DTG) 50 mg to gange dagligt (b.i.d.), når det kombineres med RIF eller 50 mg q.d. hvis RIF ikke er en del af TB-kuren, og deres spædbørn
Medicin: Dolutegravir (DTG)
Administreret i overensstemmelse med indlægssedlerne og/eller instruktionerne fra de ikke-undersøgelseskilder, som ordinerer eller leverer lægemidlerne til deltagerne
Medicin: Førstelinje TB-behandling

Deltagerne vil modtage førstelinje-TB-behandling med mindst to af følgende TB-behandlingsmidler: isoniazid (INH), rifampin (RIF), rifabutin (RFB), ethambutol (EMB), pyrazinamid (PZA) eller moxifloxacin (MFX) .

Lægemidler vil blive administreret i overensstemmelse med indlægssedlerne og/eller instruktionerne fra de ikke-undersøgelseskilder, som ordinerer eller leverer lægemidlerne til deltagerne.
Komponent 3: Arm 3.2: ATV/r eller DRV/r
Kvinder ≥ 20 ugers svangerskab, der modtager førstelinje-TB-behandling med mindst to af følgende TB-behandlingsmidler: isoniazid (INH), rifampin (RIF), rifabutin (RFB), ethambutol (EMB), pyrazinamid (PZA), moxifloxacin (MFX). ), og får atazanavir/ritonavir (ATV/r) ≥ 300/100 mg q.d. eller darunavir/ritonavir (DRV/r) ≥ 600/100 mg b.i.d. og deres spædbørn
Medicin: Førstelinje TB-behandling

Deltagerne vil modtage førstelinje-TB-behandling med mindst to af følgende TB-behandlingsmidler: isoniazid (INH), rifampin (RIF), rifabutin (RFB), ethambutol (EMB), pyrazinamid (PZA) eller moxifloxacin (MFX) .

Lægemidler vil blive administreret i overensstemmelse med indlægssedlerne og/eller instruktionerne fra de ikke-undersøgelseskilder, som ordinerer eller leverer lægemidlerne til deltagerne.

Medicin: Atazanavir/ritonavir (ATV/r)
Administreret i overensstemmelse med indlægssedlerne og/eller instruktionerne fra de ikke-undersøgelseskilder, som ordinerer eller leverer lægemidlerne til deltagerne
Medicin: Darunavir/ritonavir (DRV/r)
Administreret i overensstemmelse med indlægssedlerne og/eller instruktionerne fra de ikke-undersøgelseskilder, som ordinerer eller leverer lægemidlerne til deltagerne
Komponent 3: Arm 3.3: Lopinavir/ritonavir (LPV/r) 800/200 mg
Kvinder ≥ 20 ugers svangerskab, der modtager førstelinje-TB-behandling med mindst to af følgende TB-behandlingsmidler: isoniazid (INH), rifampin (RIF), rifabutin (RFB), ethambutol (EMB), pyrazinamid (PZA), moxifloxacin (MFX) ), og modtager lopinavir/ritonavir (LPV/r) 800/200 mg b.i.d. og deres spædbørn
Medicin: Førstelinje TB-behandling

Deltagerne vil modtage førstelinje-TB-behandling med mindst to af følgende TB-behandlingsmidler: isoniazid (INH), rifampin (RIF), rifabutin (RFB), ethambutol (EMB), pyrazinamid (PZA) eller moxifloxacin (MFX) .

Lægemidler vil blive administreret i overensstemmelse med indlægssedlerne og/eller instruktionerne fra de ikke-undersøgelseskilder, som ordinerer eller leverer lægemidlerne til deltagerne.

Medicin: Lopinavir/ritonavir (LPV/r)
Administreret i overensstemmelse med indlægssedlerne og/eller instruktionerne fra de ikke-undersøgelseskilder, som ordinerer eller leverer lægemidlerne til deltagerne
Komponent 4: Arm 4.1: Andenlinjes TB-behandlingsmidler

Kvinder ≥ 20 ugers svangerskab, der modtager mindst én af følgende anden linje TB-behandlingsmidler, og deres spædbørn:

  • Levofloxacin (LFX) 750mg - 1000mg q.d.
  • Clofazimin (CFZ) 100 mg q.d.
  • Linezolid (LZD) 300mg - 600mg q.d.
  • Bedaquilin (BDQ) 200mg tre gange om ugen (t.i.w.)
  • Delamanid (DLM) 100mg b.i.d.
  • Moxifloxacin (MFX) 400mg eller 800mg q.d. og mindst ét ​​andet anden-line TB behandlingslægemiddel under undersøgelse
Medicin: Second-line TB-behandling

Deltagerne vil modtage anden-linje-TB-behandling med mindst én af følgende anden-line-TB-behandlingsmidler:

  • Levofloxacin (LFX) 750mg - 1000mg q.d.
  • Clofazimin (CFZ) 100 mg q.d.
  • Linezolid (LZD) 300mg - 600mg q.d.
  • Bedaquilin (BDQ) 200mg tre gange om ugen (t.i.w.)
  • Delamanid (DLM) 100mg b.i.d.
  • Moxifloxacin (MFX) 400mg eller 800mg q.d. og mindst ét ​​andet anden-line TB behandlingslægemiddel under undersøgelse

Lægemidler vil blive administreret i overensstemmelse med indlægssedlerne og/eller instruktionerne fra de ikke-undersøgelseskilder, som ordinerer eller leverer lægemidlerne til deltagerne.
Komponent 5: Arm 5.1: ATV/r
Kvinder efter fødslen, der modtager ATV/r, og deres spædbørn
Medicin: Atazanavir/ritonavir (ATV/r)
Administreret i overensstemmelse med indlægssedlerne og/eller instruktionerne fra de ikke-undersøgelseskilder, som ordinerer eller leverer lægemidlerne til deltagerne
Komponent 5: Arm 5.2: DRV/r
Kvinder efter fødslen, der modtager DRV/r, og deres spædbørn
Medicin: Darunavir/ritonavir (DRV/r)
Administreret i overensstemmelse med indlægssedlerne og/eller instruktionerne fra de ikke-undersøgelseskilder, som ordinerer eller leverer lægemidlerne til deltagerne
Komponent 5: Arm 5.3: LPV/r
Kvinder efter fødslen, der modtager LPV/r, og deres spædbørn
Medicin: Lopinavir/ritonavir (LPV/r)
Administreret i overensstemmelse med indlægssedlerne og/eller instruktionerne fra de ikke-undersøgelseskilder, som ordinerer eller leverer lægemidlerne til deltagerne
Component 1: Arm 1.3: Tenofovir alafenamide (TAF) 10 mg q.d. boosted with cobicistat
Women ≥ 20 weeks gestation not receiving TB drugs and receiving tenofovir alafenamide (TAF) 10 mg q.d. boosted with cobicistat, and their infants
Medicin: Tenofoviralafenamid (TAF)
Administreret i overensstemmelse med indlægssedlerne og/eller instruktionerne fra de ikke-undersøgelseskilder, som ordinerer eller leverer lægemidlerne til deltagerne
Medicin: Cobicistat
Administreret i overensstemmelse med indlægssedlerne og/eller instruktionerne fra de ikke-undersøgelseskilder, som ordinerer eller leverer lægemidlerne til deltagerne
Component 2: Arm 2.1: Long-acting injectable formulation of cabotegravir (CAB LA)
Women ≥ 24 weeks gestation who received at least one dose of long-acting injectable formulation of cabotegravir (CAB LA) any dose during pregnancy, and their infants
Medicin: Long-acting injectable formulation of cabotegravir (CAB LA)
Administered consistent with the package inserts and/or instructions provided by the non-study sources who prescribe or supply the drugs to participants

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Number of Women Who Meet Area Under the Curve (AUC) Target in Plasma (Component 1)
Tidsramme: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 6-12 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, 12, and 24 hours post-dose.
A target AUC was derived for each drug as the 10th percentile for the non-pregnant population based on historical control data. The target AUC is 58.7 mg*h/L for Arm 1.1 and 10.0 mg*h/L for Arm 1.2. Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods. McNemar's test was not conducted for Arm 1.2 due to low sample size.
Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 6-12 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, 12, and 24 hours post-dose.
Median Maternal AUC in Plasma (Component 1)
Tidsramme: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 6-12 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, 12, and 24 hours post-dose.
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods. Wilcoxon signed-rank test was not conducted for Arm 1.2 due to low sample size.
Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 6-12 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, 12, and 24 hours post-dose.
Median Maternal Tenofovir-diphosphate (TFV-DP) Concentrations in Dried Blood Spots (DBS) (Component 1)
Tidsramme: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 6-12 weeks after delivery). Samples collected pre-dose.
TFV-DP intracellular concentrations in DBS samples. Concentrations obtained from two 7 mm punches.
Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 6-12 weeks after delivery). Samples collected pre-dose.
Median Maternal Tenofovir-diphosphate (TFV-DP) Concentrations in Peripheral Blood Mononuclear Cells (PBMCs ) (Component 1)
Tidsramme: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 6-12 weeks after delivery). Samples collected pre-dose and at 3 and 24 hours post-dose.
TFV-DP intracellular concentrations in PBMC samples.
Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 6-12 weeks after delivery). Samples collected pre-dose and at 3 and 24 hours post-dose.
Median Maternal Isoniazid (INH) AUC in Plasma (Component 3)
Tidsramme: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods. AUC reported is the AUC to the last measurable timepoint.
Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Median Maternal Rifampin (RIF) AUC in Plasma (Component 3)
Tidsramme: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods. AUC reported is the AUC to the last measurable timepoint.
Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Median Maternal Ethambutol (EMB) AUC in Plasma (Component 3)
Tidsramme: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods. AUC reported is the AUC to the last measurable timepoint.
Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Median Maternal Pyrazinamide (PZA) AUC in Plasma (Component 3)
Tidsramme: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods. AUC reported is the AUC to the last measurable timepoint. Comparison of Antepartum vs. Postpartum was not done due to low sample size.
Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Median Maternal Dolutegravir (DTG) AUC in Plasma (Component 3)
Tidsramme: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods. AUC reported is the AUC to the last measurable timepoint. The data of the P1026s arm was not reported since it's not one of the arms in this study.
Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Median Maternal Bedqauiline (BDQ) AUC in Plasma (Component 4)
Tidsramme: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods. AUC reported is the AUC to the last measurable timepoint. Wilcoxon signed-rank test was not conducted for Arm 4.1 due to low sample size.
Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Median Maternal Clofazimine (CFZ) AUC in Plasma (Component 4)
Tidsramme: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods. AUC reported is the AUC to the last measurable timepoint. Wilcoxon signed-rank test was not conducted for Arm 4.1 due to low sample size.
Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Median Maternal Delamanid (DLM) AUC in Plasma (Component 4)
Tidsramme: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods. AUC reported is the AUC to the last measurable timepoint. Wilcoxon signed-rank test was not conducted for Arm 4.1 due to low sample size.
Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Median Maternal Levofloxacin (LFX) AUC in Plasma (Component 4)
Tidsramme: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods. AUC reported is the AUC to the last measurable timepoint.
Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Median Maternal Linezolid (LZD) AUC in Plasma (Component 4)
Tidsramme: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods. AUC reported is the AUC to the last measurable timepoint. Wilcoxon signed-rank test was not conducted for Arm 4.1 due to low sample size.
Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Median Maternal Atazanavir (ATV) Breast Milk/Maternal Plasma Concentration Ratio (Component 5)
Tidsramme: Measured at 5-9 days, 2-12 weeks, and 16-24 weeks post-delivery
Breast milk and maternal plasma concentrations were collected at study visits and compared as a ratio. A higher ratio indicates the potential for higher infant drug exposure through breast milk. Only measured for mothers who met the breast milk transfer PK sampling requirements outlined in the protocol.
Measured at 5-9 days, 2-12 weeks, and 16-24 weeks post-delivery
Median Maternal Ritonavir (RTV) Breast Milk/Maternal Plasma Concentration Ratio (Component 5)
Tidsramme: Measured at 5-9 days, 2-12 weeks, and 16-24 weeks post-delivery
Breast milk and maternal plasma concentrations were collected at study visits and compared as a ratio. A higher ratio indicates the potential for higher infant drug exposure through breast milk. Only measured for mothers who met the breast milk transfer PK sampling requirements outlined in the protocol.
Measured at 5-9 days, 2-12 weeks, and 16-24 weeks post-delivery
Infant Atazanvir (ATV) Plasma Concentration (Component 5)
Tidsramme: Measured at 5-9 days, 2-12 weeks, and 16-24 weeks of life
Only measured for infants who met the breast milk transfer PK sampling requirements outlined in the protocol. The lower limit of quantitation (LLoQ) was 23.4 ng/mL for ATV.
Measured at 5-9 days, 2-12 weeks, and 16-24 weeks of life
Infant Ritonavir (RTV) Plasma Concentration (Component 5)
Tidsramme: Measured at 5-9 days, 2-12 weeks, and 16-24 weeks of life
Only measured for infants who met the breast milk transfer PK sampling requirements outlined in the protocol. The lower limit of quantitation (LLoQ) was 9.8 ng/mL for RTV.
Measured at 5-9 days, 2-12 weeks, and 16-24 weeks of life

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Median Ratio of Cord Blood Concentration to Maternal Blood Concentration (Component 1, Arms 1.1 and 1.2)
Tidsramme: Measured at time of delivery with single cord blood and single maternal blood sample.
Cord blood and maternal blood concentrations were collected and measured for the drug(s) under study at delivery and compared as a ratio.
Measured at time of delivery with single cord blood and single maternal blood sample.
Median Ratio of Cord Blood Concentration to Maternal Blood Concentration (Component 1, Arms 1.3 and 1.4)
Tidsramme: Measured at time of delivery with single cord blood and single maternal blood sample.
Cord blood and maternal blood concentrations were collected and measured for the drug(s) under study at delivery and compared as a ratio. There are four analytes for Arms 1.3 and 1.4: tenofovir alafenamide fumarate (TAF) in plasma, tenofovir-diphosphate (TFV-DP) in dried blood spots (DBS), TFV-DP in peripheral blood mononuclear cells (PBMCs), and tenofovir (TFV) in plasma. For Arm 1.3 TAF in plasma, all values were below the lower level of quantitation.
Measured at time of delivery with single cord blood and single maternal blood sample.
Median Ratio of Cord Blood Concentration to Maternal Blood Concentration (Component 3)
Tidsramme: Measured at time of delivery with single cord blood and single maternal blood sample.
Cord blood and maternal blood concentrations were collected and measured for the drugs under study at delivery and compared as a ratio. The analytes for Arm 3.1 were: isoniazid (INH), rifampin (RIF), ethambutol (EMB), pyrazinamide (PZA), and dolutegravir (DTG).
Measured at time of delivery with single cord blood and single maternal blood sample.
Median Ratio of Cord Blood Concentration to Maternal Blood Concentration (Component 4)
Tidsramme: Measured at time of delivery with single cord blood and single maternal blood sample.
Cord blood and maternal blood concentrations were collected and measured for the drugs under study at delivery and compared as a ratio. The analytes for Arm 4.1 were: bedaquiline (BDQ), clofazimine (CFZ), delamanid (DLM), levofloxacin (LFX), and linezolid (LZD).
Measured at time of delivery with single cord blood and single maternal blood sample.
Median Infant Washout Half-life of Drug After Birth (Component 1)
Tidsramme: Measured at birth (2-10 hours, 18-28 hours and 36-72 hours) and 5-9 days after birth
Infant washout PK concentrations were measured during the first 9 days of life. Half-life was calculated based on the concentrations. The analyte of Arm 1.4 is tenofovir in plasma.
Measured at birth (2-10 hours, 18-28 hours and 36-72 hours) and 5-9 days after birth
Infant Washout Half-life of Drug After Birth (Component 3)
Tidsramme: Measured at birth (2-10 hours, 18-28 hours and 36-72 hours) and 5-9 days after birth
Infant washout PK concentrations were measured during the first 9 days of life. Half-life was calculated based on the concentrations. The analytes for Arm 3.1 were: isoniazid (INH), rifampin (RIF), ethambutol (EMB), pyrazinamide (PZA), and dolutegravir (DTG).
Measured at birth (2-10 hours, 18-28 hours and 36-72 hours) and 5-9 days after birth
Infant Washout Half-life of Drug After Birth (Component 4)
Tidsramme: Measured at birth (2-10 hours, 18-28 hours and 36-72 hours) and 5-9 days after birth
Infant washout PK concentrations were measured during the first 9 days of life. Half-life was calculated based on the concentrations where it was possible to calculate. The analytes for Arm 4.1 were: bedaquiline (BDQ), clofazimine (CFZ), delamanid (DLM), levofloxacin (LFX), and linezolid (LZD).
Measured at birth (2-10 hours, 18-28 hours and 36-72 hours) and 5-9 days after birth
Maternal Breast Milk/Maternal Plasma Concentration Ratio (Components 3 and 4)
Tidsramme: Measured at 2-8 weeks postpartum (and 5-9 days and 16-24 weeks post-delivery if the requirements for breast milk transfer PK sampling are met)
Breast milk and maternal plasma concentrations were collected at study visits to be compared as a ratio, measured for mothers who met the breast milk transfer PK sampling requirements outlined in the protocol. A higher ratio indicates the potential for higher infant drug exposure through breast milk. Per the protocol, breast milk transfer sampling was not to be performed for Arm 3.1. For Arm 4.1, samples were collected but not run and have yet to be analyzed. The anticipated reporting date is April 2027.
Measured at 2-8 weeks postpartum (and 5-9 days and 16-24 weeks post-delivery if the requirements for breast milk transfer PK sampling are met)
Infant Plasma Concentration (Component 3)
Tidsramme: Measured through Week 24
Plasma concentrations as part of breast milk transfer sampling. Per the protocol, breast milk transfer sampling was not to be performed for Arm 3.1.
Measured through Week 24
Median Infant Bedaquiline (BDQ) Plasma Concentration (Component 4)
Tidsramme: Measured at 5-9 days, 2-8 weeks, and 16-24 weeks after delivery.
Infant plasma concentration as part of breast milk transfer sampling to describe the kinetics of drug transfer from mother to infant via breast milk
Measured at 5-9 days, 2-8 weeks, and 16-24 weeks after delivery.
Median Infant Clofazimine (CFZ) Plasma Concentration (Component 4)
Tidsramme: Measured at 5-9 days, 2-8 weeks, and 16-24 weeks after delivery.
Infant plasma concentration as part of breast milk transfer sampling to describe the kinetics of drug transfer from mother to infant via breast milk
Measured at 5-9 days, 2-8 weeks, and 16-24 weeks after delivery.
Median Infant Delamanid (DLM) Plasma Concentration (Component 4)
Tidsramme: Measured at 5-9 days, 2-8 weeks, and 16-24 weeks after delivery.
Infant plasma concentration as part of breast milk transfer sampling to describe the kinetics of drug transfer from mother to infant via breast milk
Measured at 5-9 days, 2-8 weeks, and 16-24 weeks after delivery.
Median Infant Levofloxacin (LFX) Plasma Concentration (Component 4)
Tidsramme: Measured at 5-9 days, 2-8 weeks, and 16-24 weeks after delivery.
Infant plasma concentration as part of breast milk transfer sampling to describe the kinetics of drug transfer from mother to infant via breast milk
Measured at 5-9 days, 2-8 weeks, and 16-24 weeks after delivery.
Median Infant Linezolid (LZD) Plasma Concentration (Component 4)
Tidsramme: Measured at 5-9 days, 2-8 weeks, and 16-24 weeks after delivery.
Infant plasma concentration as part of breast milk transfer sampling to describe the kinetics of drug transfer from mother to infant via breast milk
Measured at 5-9 days, 2-8 weeks, and 16-24 weeks after delivery.
Median Infant Dolutegravir (DTG) Plasma Concentration (Component 4)
Tidsramme: Measured at 5-9 days, 2-8 weeks, and 16-24 weeks after delivery.
Infant plasma concentration as part of breast milk transfer sampling to describe the kinetics of drug transfer from mother to infant via breast milk
Measured at 5-9 days, 2-8 weeks, and 16-24 weeks after delivery.
Median Maternal Efavirenz (EFV) AUC in Plasma (Component 4)
Tidsramme: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery).
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods.
Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery).
Median Maternal Lopinavir (LPV) AUC in Plasma (Component 4)
Tidsramme: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery).
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods.
Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery).
Median Median Atazanavir (ATV) AUC in Plasma (Component 4)
Tidsramme: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery).
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods.
Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery).
Median Maternal Darunavir (DRV) AUC in Plasma (Component 4)
Tidsramme: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery).
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods.
Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery).
Median Maternal Dolutegravir (DTG) AUC in Plasma (Component 4)
Tidsramme: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods. AUC reported is the AUC to the last measurable timepoint.
Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery). Sampling performed pre-dose and at 1, 2, 4, 6, 8, and 12 hours post-dose.
Median Maternal Raltegravir (RAL) AUC in Plasma (Component 4)
Tidsramme: Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery).
Pharmacokinetic parameters were determined by the study pharmacologists from plasma concentration-time profiles using noncompartmental methods.
Measured at 2nd trimester (2T, 20 0/7 - 26 6/7 weeks of pregnancy), 3rd trimester (3T, 30 0/7 - 37 6/7 weeks of pregnancy), and postpartum (PP, 2-8 weeks after delivery).
Number of Participants With Grade 3 or Higher Maternal Adverse Events
Tidsramme: Component 1 measured through Week 12 post-delivery; Component 3 and 4 measured through Week 8 post-delivery (except breastmilk transfer women measured through Week 24 post-delivery); Component 5 measured through Week 24 post-delivery.
Maternal Grade 3 or higher adverse events. Adverse events were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017.
Component 1 measured through Week 12 post-delivery; Component 3 and 4 measured through Week 8 post-delivery (except breastmilk transfer women measured through Week 24 post-delivery); Component 5 measured through Week 24 post-delivery.
Number of Participants With Grade 2 or Higher Infant Adverse Events
Tidsramme: Measured from entry through Week 24
Infant Grade 2 or higher adverse events. Adverse events were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017.
Measured from entry through Week 24
Number of Participants With Maternal Serious Adverse Events
Tidsramme: Component 1 measured through Week 12 post-delivery; Component 3 and 4 measured through Week 8 post-delivery (except breastmilk transfer women measured through Week 24 post-delivery); Component 5 measured through Week 24 post-delivery.
Maternal serious adverse events which were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017
Component 1 measured through Week 12 post-delivery; Component 3 and 4 measured through Week 8 post-delivery (except breastmilk transfer women measured through Week 24 post-delivery); Component 5 measured through Week 24 post-delivery.
Number of Participants With Infant Serious Adverse Events
Tidsramme: Measured from entry through Week 24
Infant serious adverse events. Adverse events were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017
Measured from entry through Week 24
Number of Participants With Grade 3 or Higher Maternal Adverse Events Assessed as Related to the Drug Under Study
Tidsramme: Component 1 measured through Week 12 post-delivery; Component 3 and 4 measured through Week 8 post-delivery (except breastmilk transfer women measured through Week 24 post-delivery); Component 5 measured through Week 24 post-delivery.
Maternal Grade 3 or higher adverse events assessed as related to the drug under study. Adverse events were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017.
Component 1 measured through Week 12 post-delivery; Component 3 and 4 measured through Week 8 post-delivery (except breastmilk transfer women measured through Week 24 post-delivery); Component 5 measured through Week 24 post-delivery.
Number of Participants With Grade 2 or Higher Infant Adverse Events Assessed as Related to the Drug Under Study
Tidsramme: Measured from entry through Week 24
Infant Grade 2 or higher adverse events assessed as related to the drug under study. Adverse events were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017
Measured from entry through Week 24
Pregnancy Outcome
Tidsramme: Measured on maternal delivery date/infant Day 0
Outcome of pregnancy categorized as live birth, stillbirth, spontaneous abortion, and etc.
Measured on maternal delivery date/infant Day 0
Median Gestational Age at Birth
Tidsramme: Measured on Day 0 (0-3 days)
Infant gestational age at birth (weeks)
Measured on Day 0 (0-3 days)
Median Infant Birth Weight
Tidsramme: Measured on Day 0 (0-3 days)
Infant birth weight (grams)
Measured on Day 0 (0-3 days)
Occurrence of Congenital Anomaly or Mitochondrial Disorder
Tidsramme: Measured from Day 0 through Week 24 for Components 1, 3, 4 and 5; measured from Day 0 through Week 5 for Component 2
Presence of any congenital anomaly or mitochondrial disorder identified in infants.
Measured from Day 0 through Week 24 for Components 1, 3, 4 and 5; measured from Day 0 through Week 5 for Component 2
Infant HIV Status
Tidsramme: Measured from Day 0 through Week 24
Infant HIV status which is determined according to diagnosis per local standard of care
Measured from Day 0 through Week 24
Maternal HIV-1 RNA
Tidsramme: Measured in 2nd Trimester,(2T, 20 0/7 to 26 6/7 weeks of pregnancy), 3rd Trimester (3T, 30 0/7 to 37 6/7 weeks of pregnancy), delivery, and PP (2-8 weeks or 6-12 weeks after delivery, depending on study arm)
Plasma HIV-1 RNA levels in the mothers as in categories. The highest value of the lower limits of quantitation (LLoQ) for each arm was used for categorizations. The LLoQs are: Arm 1.1 - 40 copies/mL, Arm 1.2 - 20 copies/mL, Arm 1.3 and Arm 1.4 - 200 copies/mL, Arm 3.1 - 40 copies/mL, and Arm 4.1 - 50 copies/mL.
Measured in 2nd Trimester,(2T, 20 0/7 to 26 6/7 weeks of pregnancy), 3rd Trimester (3T, 30 0/7 to 37 6/7 weeks of pregnancy), delivery, and PP (2-8 weeks or 6-12 weeks after delivery, depending on study arm)

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Samarbejdspartnere

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute of Mental Health (NIMH)
Merck Sharp & Dohme LLC
Gilead Sciences
ViiV Healthcare
International Maternal Pediatric Adolescent AIDS Clinical Trials Group

Efterforskere

  • Studiestol: Mark Mirochnick, MD, Boston University

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Hjælpsomme links

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

1. september 2021

Primær færdiggørelse (Faktiske)

24. april 2025

Studieafslutning (Faktiske)

10. juli 2025

Datoer for studieregistrering

Først indsendt

5. marts 2020

Først indsendt, der opfyldte QC-kriterier

14. august 2020

Først opslået (Faktiske)

19. august 2020

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

26. august 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

3. august 2026

Sidst verificeret

1. august 2026

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • IMPAACT 2026
  • 38609 (Registry Identifier: DAIDS-ES Registry Number)

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

JA

IPD-planbeskrivelse

Individuelle deltagerdata, der ligger til grund, resulterer i offentliggørelsen efter afidentifikation.

IPD-delingstidsramme

Begyndende 3 måneder efter offentliggørelsen og tilgængelig i hele finansieringsperioden for International Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) Network af NIH.

IPD-delingsadgangskriterier

  • Med hvem?

    • Forskere, der giver et metodisk forsvarligt forslag til brug af data, som er godkendt af IMPAACT Network.

  • Til hvilke typer analyser?

    • At nå målene i forslaget godkendt af IMPAACT-netværket.

  • Ved hvilken mekanisme vil data blive gjort tilgængelige?

    • Forskere kan indsende en anmodning om adgang til data ved hjælp af IMPAACT "Data Request"-formularen på: https://www.impaactnetwork.org/resources/study-proposals.htm. Forskere af godkendte forslag skal underskrive en IMPAACT-databrugsaftale, før de modtager dataene

IPD-deling Understøttende informationstype

  • STUDY_PROTOCOL
  • SAP

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Abonner