Tenofovir/Emtricitabine for PMTCT in Africa and Asia (ANRS 12109 TEmAA)

This study has been completed.
Sponsor:
Collaborators:
European and Developing Countries Clinical Trials Partnership (EDCTP)
Gilead Sciences
Information provided by (Responsible Party):
French National Agency for Research on AIDS and Viral Hepatitis
ClinicalTrials.gov Identifier:
NCT00334256
First received: June 6, 2006
Last updated: December 2, 2011
Last verified: December 2011
  Purpose

To study the pharmacokinetic properties, safety and viral resistance pattern of the combination of tenofovir disoproxil fumarate and emtricitabine in HIV-1-infected pregnant women and their newborns, with a view to prevention of mother-to-child transmission (PMTCT) of HIV-1 in Africa and Asia.


Condition Intervention Phase
HIV Infection
Pregnancy
Drug: Tenofovir (TDF)
Drug: Emtricitabine (FTC)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Phase II Trial, Multicentre, Opened Label Evaluating the Pharmacokinetics and the Safety and Toxicity of the Tenofovir-Emtricitabine Combination in Pregnant Women and Infants in Africa and Asia

Resource links provided by NLM:


Further study details as provided by French National Agency for Research on AIDS and Viral Hepatitis:

Primary Outcome Measures:
  • Pharmacokinetic parameters of TDF and FTC in the mother and child [ Time Frame: during labor and first 72 hours of life ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety of TDF + FTC in pregnant women [ Time Frame: during labor and 2 months after delivery ] [ Designated as safety issue: Yes ]
  • Safety of TDF + FTC in children [ Time Frame: 2 months after birth ] [ Designated as safety issue: Yes ]
  • Frequency of viral resistance to TDF and FTC in the mothers and in the infected children [ Time Frame: at D2 and W4 postpartum/postnatal ] [ Designated as safety issue: No ]
  • Effect of the antiretroviral combination on maternal viral load [ Time Frame: D2 and W4 post-partum ] [ Designated as safety issue: No ]
  • Estimation of the mother-to-child HIV-1 transmission rate (exploratory study) [ Time Frame: D3, W4, W6 ] [ Designated as safety issue: No ]

Enrollment: 72
Study Start Date: October 2006
Study Completion Date: December 2009
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Detailed Description:

Single-dose nevirapine (sdNVP) is the option of choice for the prevention of mother-to-child transmission (PMTCT) of HIV-1 in countries with limited resources. However, the use of sdNVP results in resistance mutations with an estimated frequency at of least 15 to 70% in women at W4-W6 postpartum. These mutations could compromise the success of subsequent treatments of mother and child with antiretroviral combinations that include NVP. Pre-clinical and clinical studies suggest that a combination of TDF and FTC, drugs with interesting pharmacokinetic properties that may be a useful alternative or complement to sdNVP.

The objectives are to study the pharmacokinetic properties, safety and viral resistance pattern of the combination of tenofovir disoproxil fumarate {TDF, 600 mg} and emtricitabine {FTC, 400 mg}) in HIV-1-infected pregnant women and their newborns, with a view to prevention of mother-to-child transmission (PMTCT) of HIV-1 in Africa and Asia.

Phase II trial, multicentre, open-label will be conducted in two steps with 30 mother-infant pairs per step and with a balanced allocation in Abidjan (Côte d'Ivoire), Soweto (South Africa) and Phnom Penh (Cambodia):

Step 1: administration of TDF/FTC to the mother; Step 2: administration of TDF/FTC to the mother and the newborn.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Women received voluntary counselling and testing and knows her serological status
  • HIV-1 or HIV-1+2 infection whose serological diagnosis is confirmed by two samples
  • Aged 18 years or over on the day of the inclusion
  • Ongoing pregnancy of between 28 and 38 weeks of gestation from the day of the inclusion. This estimate will be based on the date of the last menstruation, or ultrasound scan, or uterine height measurement
  • Indication for antiretroviral treatment in the Prevention of Mother-To-Child-Transmission (PMTCT), in line with international or national recommendations in force: WHO's clinical stage 1, 2 and CD4≥200/mm3or stage 3 and CD4≥350/mm3 (No indication of antiretroviral treatment)
  • Haemoglobin over 8 g/dL in the month preceding inclusion
  • Blood creatinine less than three times the upper limit of normal values
  • Creatinine clearance > 49 mL/min
  • Transaminases (ALAT or ASAT) less than five times the upper limit of normal values
  • Neutrophils ≥750/mm3
  • No hypersensitivity to emtricitabine, tenofovir, tenofovir disoproxil fumarate, zidovudine, nevirapine or to the excipients
  • Signed informed-consent form by the woman and, by the father of the child to be born
  • Planned delivery in a hospital setting and stay for at least 72 hours afterwards
  • Agreement to take no other medication during the trial without telling the investigator
  • Naïve to all antiretroviral treatment and to antiretroviral prophylaxis for PMTCT during a previous pregnancy
  • Permanent residence close enough to the study centre to enable follow-up as stipulated in the protocol

Exclusion Criteria:

  • Under 18 years of age
  • Infected by HIV-2 alone
  • One of the two parents (father) refuses to sign the consent to participate (available only for Abidjan and Phnom Penh) or the mother ( for the Soweto site)
  • Indication for antiretroviral treatment (stage 4 or CD4 <200/mm3 or stage 3 and CD4 <350/mm3)
  • Has already taken antiretrovirals, including any exposure to previous treatment or prophylaxis for PMTCT, before inclusion in the study
  • Use of drugs which can interfere with the study such as :

    • nephrotoxic drugs amphotericin B, ganciclovir, valganciclovir or cidofovir, foscarnet, aminosides, pentamidine, cisplatin
    • anticoagulants (heparin)
  • Regular use of drug or alcohol
  • Health problem requiring systematic treatment or hospitalization
  • Severe pregnancy disease (pre-eclampsia) that is life-threatening for the mother, the infant, or for both
  • Severe vomiting preventing ingestion of tablets
  • Refuses to give birth at a study site and to stay in hospital for at least 72 hours afterwards
  • Renal insufficiency defined by blood creatinine more than three times the upper limit of normal values
  • Creatinine clearance under or equal to 49 mL/min
  • Hepatic insufficiency defined by transaminases (ALAT or ASAT) more than five times the upper limit of normal values
  • Neutrophils <750/mm3
  • Haemoglobin <8 grams/dL in the month preceding inclusion
  • Hypersensitivity to emtricitabine, tenofovir, tenofovir disoproxil fumarate, zidovudine, nevirapine or to the excipients
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00334256

Locations
Cambodia
Calmette Hospital
Phnom Penh, Cambodia
Côte D'Ivoire
Centre de Prise en Charge et de Formation ACONDA
Abidjan, Côte D'Ivoire
South Africa
PHRU
Soweto, South Africa
Sponsors and Collaborators
French National Agency for Research on AIDS and Viral Hepatitis
European and Developing Countries Clinical Trials Partnership (EDCTP)
Gilead Sciences
Investigators
Study Chair: François Dabis, MD, PhD Université Bordeaux 2
Principal Investigator: Didier K Ekouevi, MD, PhD Programme PACCI Abidjan
  More Information

Additional Information:
Publications:
Responsible Party: French National Agency for Research on AIDS and Viral Hepatitis
ClinicalTrials.gov Identifier: NCT00334256     History of Changes
Other Study ID Numbers: ANRS 12109 TEmAA
Study First Received: June 6, 2006
Last Updated: December 2, 2011
Health Authority: Cote d'Ivoire: Ministry of AIDS

Keywords provided by French National Agency for Research on AIDS and Viral Hepatitis:
PMTCT
Resistance
HIV infection
Pregnancy

Additional relevant MeSH terms:
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
Tenofovir
Tenofovir disoproxil
Emtricitabine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on July 20, 2014