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Universal Use of EFV-TDF-FTC and AZT-3TC-LPV/r Combinations for HIV-1 PMTCT in Pregnant and Breastfeeding Women : a Phase 3 Trial (UMA)

14 februari 2012 bijgewerkt door: French National Agency for Research on AIDS and Viral Hepatitis

Safety and Efficacy of the Universal Use of EFV-TDF-FTC and AZT-3TC-LPV/r Combinations in Pregnant and Breastfeeding Women to Prevent mother-to Child Transmission of HIV-1 o, Resource-limited Settings: A Multicentre Randomized Phase 3 Clinical Trial

To assess the maternal and infant safety of a single daily fixed-dose combination of TDF/FTC/EFV (Atripla®), compared to the association of LPV/r (Kaletra® or Aluvia®) and 3TC/ZDV (Combivir®) given to African women to prevent overall MTCT in populations practicing breastfeeding.

Studie Overzicht

Toestand

Ingetrokken

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

The prevention of MTCT during pregnancy and through breastfeeding exposure remains challenging to date in most resource-limited settings. Peripartum HIV transmission is already amenable to ARV interventions. These ARV regimens, partially efficacious are insufficiently used despite their apparent simplicity. The postnatal transmission via breastfeeding remains a serious additional threat.

This is a multicentric, non-inferiority, randomized controlled trial aiming at assessing the maternal and infant safety of a single daily fixed-dose combination of TDF/FTC/EFV (Atripla®), compared to the association of LPV/r (Kaletra® or Aluvia®) and 3TC/ZDV (Combivir®) given to African women (in Cote d'Ivoire an in Zambia) to prevent MTCT overall in breastfeeding population.

The fixed-dose combination of Tenofovir/Emtricitabine/Efavirenz (TDF/FTC/EFV or Atripla®) is a highly effective HAART combination and the simplest ARV regimen currently available in resource-limited settings and is therefore likely to become soon the lead first-line HAART regimen for adults in such settings. Its anticipated widespread prescription in women of childbearing age requires the proper documentation of its use in pregnancy and during breastfeeding.

The combination of ZDV/3TC (Combivir®) and Lopinavir/ritonavir (LPV/r) (Kaletra® or Aluvia®) is chosen as a reference regimen as it is one of the most commonly used first-line HAART for adults and the reference regimen for PMTCT in industrialised settings.

The maternal ARV regimen will be initiated as soon as possible from 20 weeks of gestation until at least the cessation of breastfeeding (with the advice to cease at six months). The decision to stop or continue the maternal ARV regimen after breastfeeding cessation will be based on the baseline maternal CD4 count and the maternal clinical stage at baseline and/or at breastfeeding cessation. A woman with a baseline CD4 <500 cells/ml will always be proposed to continue her treatment after breastfeeding cessation. A woman with a baseline CD4 count >500 will be asked to stop her treatment after breastfeeding cessation unless she has reached the WHO clinical stage IV at that time.

Infants will receive daily Zidovudine syrup from birth during the first week of life, or an updated ARV post-exposure prophylaxis recommended by WHO when women receive HAART.

Studietype

Ingrijpend

Fase

  • Fase 3

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Ivoorkust
      • Abidjan, Ivoorkust
        • Programme PAC-CI, site ANRS
  • Zambia
      • Lusaka, Zambia
        • Center for Infectious Desease Reserach in Zambia

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Vrouw

Beschrijving

Inclusion Criteria:

  • being pregnant, presenting in at least the 20th week of pregnancy and no later than 2 weeks before the expected term;
  • at least 18 years of age;
  • diagnosed as infected with HIV-1 only;
  • not currently taking any ARV drugs;
  • having not been exposed to NVP in the 6 months preceding enrolment;
  • willing to breastfeed their forthcoming child;
  • residing and planning to continue to reside within the predefined catchment areas until 12 months after delivery;
  • being able to give informed consent for enrolment in the study;
  • lacking any medical contraindication to any of the proposed ARV medications;
  • and accepting the principle of being randomized to receive one of the ARV regimens evaluated within the study, to prevent MTCT and for their own health when required.

Exclusion Criteria:

  • presenting within 2 weeks before the expected term;
  • currently taking ARV drugs;
  • having been exposed to NVP in the 6 months preceding enrolment;
  • not willing to breastfeed their forthcoming child;
  • having severe renal insufficiency (creatin clearance < 60ml/min);
  • diagnosed as infected with HIV-2 only or dually infected HIV-1 and HIV-2;
  • hemoglobin < 7 g/dL in the month preceding inclusion
  • HBs Ag positive

Women meeting one of the three last exclusion criteria (HIV-2 infection or co-infection, hemoglobin < 7 g/dL, HBs Ag positive) will not be randomized but will all received Atripla and be followed-up in an ancillary open cohort according the same procedures and agenda.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Preventie
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Actieve vergelijker: Atripla (R)
Geneesmiddel: Efavirenz-Tenofovir-Emtricitabine
Atripla (R) : Efavirenz 600 mg - Tenofovir 300 mg - Emtricitabine 200 mg; Dosage : 1 pill/day
Actieve vergelijker: Combivir (R) + Kaletra (R) or Aluvia (R)
Geneesmiddel: Zidovudine-Lamivudine-Lopinavir/Ritonavir

Combivir (R) : Zidovudine 300 mg - Lamivudine 150 mg Dosage : 1 pill twice a day

Kaletra (R) or Aluvia (R) : Lopinavir 200 mg / Ritonavir 50 mg Dosage : 2 or 3 pills twice a day

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Tijdsspanne
cumulative occurence of : -adverse pregnancy outcomes (spontaneous abortion, stillbirth, congenital abnormality requiring surgical correction in children < 1 yr of age); -paediatric HIV infection; -infant mortality
Tijdsspanne: at 6 and 12 months following delivery/birth
at 6 and 12 months following delivery/birth

Secundaire uitkomstmaten

Uitkomstmaat
Tijdsspanne
occurence of grade 4 events in treated women, and of grade 3 or 4 events in ARV-exposed infants
Tijdsspanne: at 6 and 12 months following delivery/birth
at 6 and 12 months following delivery/birth
frequency of virological failure (>300 copies/mL) and viral resistance profile
Tijdsspanne: at 6 month and 12 months post-delivery
at 6 month and 12 months post-delivery
frequency of premature delivery (<37 weeks) and frequency of low birth weight (<2500 g)
Tijdsspanne: at delivery/birth
at delivery/birth
cumulative incidence of paediatric HIV infection
Tijdsspanne: at 12 months after delivery
at 12 months after delivery
tolerability of the ARV combination in treated women
Tijdsspanne: at 6 and 12 months following delivery/birth
at 6 and 12 months following delivery/birth

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

French National Agency for Research on AIDS and Viral Hepatitis

Medewerkers

GlaxoSmithKline
Merck Sharp & Dohme LLC
Gilead Sciences
Abbott

Onderzoekers

  • Studie stoel: Didier K Ekouevi, MD, PhD, Programme PACCI Abidjan, Cote d'Ivoire
  • Studie stoel: François Dabis, MD, PhD, Bordeaux 2 University, France

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 januari 2010

Primaire voltooiing (Verwacht)

1 januari 2013

Studie voltooiing (Verwacht)

1 juni 2013

Studieregistratiedata

Eerst ingediend

8 juli 2009

Eerst ingediend dat voldeed aan de QC-criteria

8 juli 2009

Eerst geplaatst (Schatting)

9 juli 2009

Updates van studierecords

Laatste update geplaatst (Schatting)

15 februari 2012

Laatste update ingediend die voldeed aan QC-criteria

14 februari 2012

Laatst geverifieerd

1 februari 2012

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • ANRS 12200 UMA

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