Etravirine Pharmacokinetics and HIV Viral Load in Breast Milk and Plasma

This study has been completed.
Sponsor:
Collaborator:
Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Information provided by (Responsible Party):
LaShonda, University of Southern California
ClinicalTrials.gov Identifier:
NCT01625169
First received: June 12, 2012
Last updated: August 11, 2014
Last verified: August 2014
  Purpose

HIV positive pregnant women who receive potent combination antiretroviral therapy over at least the last trimester of pregnancy, and who have proper obstetric interventions and are able to avoid breast feeding, decrease the risk of having an infected infant to about 1%. Breast milk HIV-1 RNA (cell free) viral load is significantly associated with breast milk transmission, and a 2-fold increased risk of transmission associated with every 10-fold increase in breast milk viral load has been reported. In addition, cell associated virus (HIV DNA) was associated with a significant increase in risk of transmission independent of the level of cell-free viral RNA.

However, multiple studies of HIV positive women giving birth have shown that exclusive breast-feeding carries a much lower risk of HIV transmission than mixed breast-feeding (defined as breast milk along with complementary food, other milk, and/or infant formula). The proposed study will measure the antiretroviral (ARV) drug etravirine concentrations in blood and breast milk in postpartum HIV positive women on HAART therapy. The short-term goal is to determine how much etravirine penetrates into breast milk, and whether it leads to undetectable HIV viral load in the breast milk and therefore has the potential to decrease the risk of transmission of HIV through breast milk. The long term goal is to see if breast milk HIV levels can be lowered sufficiently to prevent maternal to child transmission (MTCT) of HIV in infants receiving only breast feeding in resource poor areas.


Condition Intervention
HIV
Drug: Etravirine pharmacokinetics in breast milk and plasma

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Antiretroviral Drug Concentrations and HIV Viral Load in Breast Milk and Plasma in HIV+ Women Receiving HAART (Highly Active Antiretroviral Therapy) Therapy: Etravirine (ETR) Pharmacokinetics (PK) in Breast Milk and Plasma

Resource links provided by NLM:


Further study details as provided by University of Southern California:

Primary Outcome Measures:
  • Peak Plasma Concentration of Etravirine in Plasma [ Time Frame: Day 5 ] [ Designated as safety issue: No ]

    Cmax ng/ml

    Note: One participant did not complete the Day 5 evaluation.


  • Peak Concentration of Etravirine in Breast Milk [ Time Frame: day 5 ] [ Designated as safety issue: No ]

    Cmax ng/ml

    Note: One participant did not complete the Day 5 evaluation.


  • Peak Concentration of Etravirine in Breast Milk [ Time Frame: day 14 ] [ Designated as safety issue: No ]
    Cmax ng/mL

  • Peak Plasma Concentration of Etravirine in Plasma [ Time Frame: day 14 ] [ Designated as safety issue: No ]
    Cmax ng/mL

  • Area Under the Curve (AUC) 0-12 for Plasma [ Time Frame: Day 5: 0, 2,4, 8 and 24 hours post dose ] [ Designated as safety issue: No ]
    AUC 0-12 ng*hr/ml

  • Area Under the Curve (AUC) 0-12 for Plasma [ Time Frame: Day 14: 0, 2,4, 8 and 24 hours post dose ] [ Designated as safety issue: No ]
    AUC 0-12 ng*hr/ml

  • Area Under the Curve (AUC) 0-12 for Breast Milk [ Time Frame: Day 5 ] [ Designated as safety issue: No ]
    AUC 0-12 ng*hr/ml

  • Area Under the Curve (AUC) 0-12 for Breast Milk [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
    AUC 0-12 ng*hr/ml


Secondary Outcome Measures:
  • HIV Viral Load in Breast Milk and Plasma [ Time Frame: Day 5 ] [ Designated as safety issue: No ]
    Positive HIV RNA in breast milk and plasma- LDL 40 copies/ml

  • HIV Viral Load in Breast Milk and Plasma [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
    Positive HIV RNA in breast milk and plasma- LDL 40 copies/ml


Enrollment: 9
Study Start Date: April 2010
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
HIV + pregnant women
Etravirine pharmacokinetics in breast milk and plasma. Etravirine 200mg PO BID for 14 days with PK on days 5 and 14
Drug: Etravirine pharmacokinetics in breast milk and plasma
HIV+ pregnant women will receive etravirine 200mg PO BID for 14 days postpartum. PK will be done on postpartum days 5 and 14.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. HIV+ pregnant women on HAART for the prevention of MTCT w/ undetectable viral load at time of delivery (w/i 30 days of delivery).
  2. 18 years and older
  3. Only women who are deemed by the physician as being capable of understanding that HIV positive women should not breastfeed will be approached.
  4. Life expectancy greater than 6 months
  5. No known allergies to etravirine
  6. Willingness of subject to adhere to protocol requirements.

Exclusion Criteria:

  1. Pregnant women with medical or psychological contraindications to breast milk expression.
  2. Requirements for prohibited medications:

    • ARV: Tipranavir/ritonavir, fosamprenavir/ritonavir, atazanavir/ritonavir, and protease inhibitors administered without ritonavir, nonnucleoside reverse transcriptase inhibitor (NNRTIs).
    • Alternative/CAM: St. John's wort
    • Anticonvulsants: Phenobarbital, carbamazepine , phenytoin
    • Anti-infectives: Rifampin
  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: NCT01625169

Locations
United States, California
LAC+USC MCA Clinic
Los Angeles, California, United States, 90033
Sponsors and Collaborators
University of Southern California
Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Investigators
Principal Investigator: LaShonda Y Spencer, MD University of Southern California
  More Information

No publications provided

Responsible Party: LaShonda, Assistant Prof of Clinical Pediatrics, University of Southern California
ClinicalTrials.gov Identifier: NCT01625169     History of Changes
Other Study ID Numbers: HS-09-00698
Study First Received: June 12, 2012
Results First Received: June 9, 2014
Last Updated: August 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Southern California:
Pharmacokinetics
HIV
Breast milk

Additional relevant MeSH terms:
Etravirine
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

ClinicalTrials.gov processed this record on September 22, 2014