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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)

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ClinicalTrials.gov Identifier: NCT00936195
Recruitment Status : Withdrawn (faillure to obtain insurance because of refusal from insurance companies)
First Posted : July 9, 2009
Last Update Posted : February 15, 2012
Sponsor:
Collaborators:
Gilead Sciences
Merck Sharp & Dohme Corp.
GlaxoSmithKline
Abbott
Information provided by (Responsible Party):
French National Agency for Research on AIDS and Viral Hepatitis

Study Description
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Brief 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.

Condition or disease Intervention/treatment Phase
HIV Infection Pregnancy Breastfeeding HIV Infections Drug: Efavirenz-Tenofovir-Emtricitabine Drug: Zidovudine-Lamivudine-Lopinavir/Ritonavir Phase 3

Detailed 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.


Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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
Study Start Date : January 2010
Estimated Primary Completion Date : January 2013
Estimated Study Completion Date : June 2013

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U.S. FDA Resources

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Atripla (R) Drug: Efavirenz-Tenofovir-Emtricitabine
Atripla (R) : Efavirenz 600 mg - Tenofovir 300 mg - Emtricitabine 200 mg; Dosage : 1 pill/day
Active Comparator: Combivir (R) + Kaletra (R) or Aluvia (R) Drug: 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


Outcome Measures
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Primary Outcome Measures :
  1. 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 [ Time Frame: at 6 and 12 months following delivery/birth ]

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

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.

Contacts and Locations
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00936195


Locations
Côte D'Ivoire
Programme PAC-CI, site ANRS
Abidjan, Côte D'Ivoire
Zambia
Center for Infectious Desease Reserach in Zambia
Lusaka, Zambia
Sponsors and Collaborators
French National Agency for Research on AIDS and Viral Hepatitis
Gilead Sciences
Merck Sharp & Dohme Corp.
GlaxoSmithKline
Abbott
Investigators
Study Chair: Didier K Ekouevi, MD, PhD Programme PACCI Abidjan, Cote d'Ivoire
Study Chair: François Dabis, MD, PhD Bordeaux 2 University, France
More Information
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party: French National Agency for Research on AIDS and Viral Hepatitis
ClinicalTrials.gov Identifier: NCT00936195     History of Changes
Other Study ID Numbers: ANRS 12200 UMA
First Posted: July 9, 2009    Key Record Dates
Last Update Posted: February 15, 2012
Last Verified: February 2012

Keywords provided by French National Agency for Research on AIDS and Viral Hepatitis:
HIV
pregnancy
breastfeeding
 PMTCT
ARV treatment
treatment naive

Additional relevant MeSH terms:
Infection
Communicable Diseases
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Ritonavir
Lopinavir
 Tenofovir
Lamivudine
Emtricitabine
Zidovudine
Lamivudine, zidovudine drug combination
Efavirenz
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors