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

HIV Infections Clinical Trial

— UMA  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00936195
• Other study ID #: ANRS 12200 UMA
• Status: Withdrawn
• Phase: Phase 3
• First received: July 8, 2009
• Last updated: February 14, 2012
• Start date: January 2010
• Est. completion date: June 2013

Study information

• Verified date: February 2012
• Source: French National Agency for Research on AIDS and Viral Hepatitis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Cote d'Ivoire: Ministry of Health and Public Hygiene
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Breastfeeding
• HIV Infection
• HIV Infections
• Infection
• Pregnancy

Intervention

Drug:
• Efavirenz-Tenofovir-Emtricitabine
Atripla (R) : Efavirenz 600 mg - Tenofovir 300 mg - Emtricitabine 200 mg; Dosage : 1 pill/day
• 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

Locations

Country	Name	City	State
Côte D'Ivoire	Programme PAC-CI, site ANRS	Abidjan
Zambia	Center for Infectious Desease Reserach in Zambia	Lusaka

Sponsors (5)

Lead Sponsor	Collaborator
French National Agency for Research on AIDS and Viral Hepatitis	Abbott, Gilead Sciences, GlaxoSmithKline, Merck Sharp & Dohme Corp.

Countries where clinical trial is conducted

Côte D'Ivoire,  Zambia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		at 6 and 12 months following delivery/birth	Yes
Secondary	occurence of grade 4 events in treated women, and of grade 3 or 4 events in ARV-exposed infants		at 6 and 12 months following delivery/birth	Yes
Secondary	frequency of virological failure (>300 copies/mL) and viral resistance profile		at 6 month and 12 months post-delivery	No
Secondary	frequency of premature delivery (<37 weeks) and frequency of low birth weight (<2500 g)		at delivery/birth	Yes
Secondary	cumulative incidence of paediatric HIV infection		at 12 months after delivery	No
Secondary	tolerability of the ARV combination in treated women		at 6 and 12 months following delivery/birth	Yes