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)
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
Descripción general del estudio
Estado
Intervención / Tratamiento
Descripción detallada
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.
Tipo de estudio
Fase
- Fase 3
Contactos y Ubicaciones
Ubicaciones de estudio
-
-
-
Abidjan, Costa de Marfil
- Programme PAC-CI, site ANRS
-
-
-
-
-
Lusaka, Zambia
- Center for Infectious Desease Reserach in Zambia
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
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.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Prevención
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Comparador activo: Atripla (R)
|
Atripla (R) : Efavirenz 600 mg - Tenofovir 300 mg - Emtricitabine 200 mg; Dosage : 1 pill/day
|
|
Comparador activo: Combivir (R) + Kaletra (R) or Aluvia (R)
|
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 |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
|---|---|
|
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
Periodo de tiempo: at 6 and 12 months following delivery/birth
|
at 6 and 12 months following delivery/birth
|
Medidas de resultado secundarias
Medida de resultado |
Periodo de tiempo |
|---|---|
|
occurence of grade 4 events in treated women, and of grade 3 or 4 events in ARV-exposed infants
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: at delivery/birth
|
at delivery/birth
|
|
cumulative incidence of paediatric HIV infection
Periodo de tiempo: at 12 months after delivery
|
at 12 months after delivery
|
|
tolerability of the ARV combination in treated women
Periodo de tiempo: at 6 and 12 months following delivery/birth
|
at 6 and 12 months following delivery/birth
|
Colaboradores e Investigadores
Investigadores
- Silla de estudio: Didier K Ekouevi, MD, PhD, Programme PACCI Abidjan, Cote d'Ivoire
- Silla de estudio: François Dabis, MD, PhD, Bordeaux 2 University, France
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Anticipado)
Finalización del estudio (Anticipado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Procesos Patológicos
- Infecciones por virus de ARN
- Enfermedades virales
- Infecciones transmitidas por la sangre
- Enfermedades De Transmisión Sexual Virales
- Enfermedades de transmisión sexual
- Infecciones por lentivirus
- Infecciones por retroviridae
- Síndromes de deficiencia inmunológica
- Enfermedades del sistema inmunológico
- Atributos de la enfermedad
- Enfermedades de virus lentos
- Infecciones por VIH
- Infecciones
- Enfermedades contagiosas
- Síndrome de inmunodeficiencia adquirida
- Mecanismos moleculares de acción farmacológica
- Agentes antiinfecciosos
- Agentes Antivirales
- Inhibidores de la transcriptasa inversa
- Inhibidores de la síntesis de ácidos nucleicos
- Inhibidores de enzimas
- Agentes Anti-VIH
- Agentes antirretrovirales
- Antimetabolitos
- Inhibidores de la proteasa
- Inhibidores del citocromo P-450 CYP3A
- Inhibidores de enzimas del citocromo P-450
- Inductores de enzimas de citocromo P-450
- Inductores de citocromo P-450 CYP3A
- Inhibidores de la proteasa del VIH
- Inhibidores de la proteasa viral
- Inductores de citocromo P-450 CYP2B6
- Inhibidores del citocromo P-450 CYP2C9
- Inhibidores del citocromo P-450 CYP2C19
- Tenofovir
- Emtricitabina
- Ritonavir
- Lopinavir
- Lamivudina
- Zidovudina
- Efavirenz
- Combinación de fármacos lamivudina, zidovudina
Otros números de identificación del estudio
- ANRS 12200 UMA
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .
Ensayos clínicos sobre Infecciones por VIH
-
Icahn School of Medicine at Mount SinaiIRRASReclutamientoHemorragia Intraventricular (HIV)Estados Unidos
-
Yale UniversityTerminadoPrecocidad | Recién nacidos de muy bajo peso al nacer | Hemorragia Intraventricular (HIV) | Sangrado en el cerebroEstados Unidos
-
China Medical University HospitalDesconocidoDisplasia broncopulmonar | Bebés extremadamente prematuros | TLP grave que las terapias convencionales han fallado | Sin anomalías congénitas graves | no Hiv Severa Ni FPV QuísticaTaiwán
Ensayos clínicos sobre Efavirenz-Tenofovir-Emtricitabine
-
University of North Carolina, Chapel HillBristol-Myers Squibb; Gilead SciencesTerminadoInfecciones por VIH | Infección aguda por VIHEstados Unidos
-
St Stephens Aids TrustViiV HealthcareDesconocido
-
National Institute of Allergy and Infectious Diseases...TerminadoInfecciones por VIHEstados Unidos, Sudáfrica, Tailandia, Botsuana, Brasil, Tanzania, Zimbabue, India, Uganda
-
University of HawaiiGilead SciencesDesconocido
-
University of Alabama at BirminghamBristol-Myers SquibbTerminado
-
Professor Francois VenterUniversity of Cape TownTerminadoTuberculosis | Infección por VIH-1Sudáfrica
-
St Stephens Aids TrustTerminadoInfecciones por VIH | Infección por VIHReino Unido
-
French National Agency for Research on AIDS and...Merck Sharp & Dohme LLC; Gilead Sciences; Institut de Médecine et d'Epidémiologie...Terminado
-
Merck Sharp & Dohme LLCTerminado