Etravirine Pharmacokinetics and HIV Viral Load in Breast Milk and Plasma

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

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.

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Drug: Etravirine pharmacokinetics in breast milk and plasma

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • LAC+USC MCA Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Plasma Concentration of Etravirine in Plasma	Cmax ng/ml Note: One participant did not complete the Day 5 evaluation.	Day 5
Peak Concentration of Etravirine in Breast Milk	Cmax ng/ml Note: One participant did not complete the Day 5 evaluation.	day 5
Peak Concentration of Etravirine in Breast Milk	Cmax ng/mL	day 14
Peak Plasma Concentration of Etravirine in Plasma	Cmax ng/mL	day 14
Area Under the Curve (AUC) 0-12 for Plasma	AUC 0-12 ng*hr/ml	Day 5: 0, 2,4, 8 and 24 hours post dose
Area Under the Curve (AUC) 0-12 for Plasma	AUC 0-12 ng*hr/ml	Day 14: 0, 2,4, 8 and 24 hours post dose
Area Under the Curve (AUC) 0-12 for Breast Milk	AUC 0-12 ng*hr/ml	Day 5
Area Under the Curve (AUC) 0-12 for Breast Milk	AUC 0-12 ng*hr/ml	Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HIV Viral Load in Breast Milk and Plasma	Positive HIV RNA in breast milk and plasma- LDL 40 copies/ml	Day 5
HIV Viral Load in Breast Milk and Plasma	Positive HIV RNA in breast milk and plasma- LDL 40 copies/ml	Day 14

Collaborators and Investigators

• Sponsor: University of Southern California
• Collaborators: Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
• Investigators: Principal Investigator: LaShonda Y Spencer, MD, University of Southern California

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: June 12, 2012
• First Submitted That Met QC Criteria: June 20, 2012
• First Posted (Estimate): June 21, 2012

Study Record Updates

• Last Update Posted (Estimate): August 13, 2014
• Last Update Submitted That Met QC Criteria: August 11, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: HIV; Pharmacokinetics; Breast milk
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Etravirine
• Other Study ID Numbers: HS-09-00698