Etravirine Pharmacokinetics and HIV Viral Load in Breast Milk and Plasma

HIV Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01625169
• Other study ID #: HS-09-00698
• Status: Completed
• Phase: N/A
• First received: June 12, 2012
• Last updated: August 11, 2014
• Start date: April 2010
• Est. completion date: December 2012

Study information

• Verified date: August 2014
• Source: University of Southern California
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• HIV

Intervention

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.

Locations

Country	Name	City	State
United States	LAC+USC MCA Clinic	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
University of Southern California	Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peak Plasma Concentration of Etravirine in Plasma	Cmax ng/ml; Note: One participant did not complete the Day 5 evaluation.	Day 5	No
Primary	Peak Concentration of Etravirine in Breast Milk	Cmax ng/ml; Note: One participant did not complete the Day 5 evaluation.	day 5	No
Primary	Peak Concentration of Etravirine in Breast Milk	Cmax ng/mL	day 14	No
Primary	Peak Plasma Concentration of Etravirine in Plasma	Cmax ng/mL	day 14	No
Primary	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	No
Primary	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	No
Primary	Area Under the Curve (AUC) 0-12 for Breast Milk	AUC 0-12 ng*hr/ml	Day 5	No
Primary	Area Under the Curve (AUC) 0-12 for Breast Milk	AUC 0-12 ng*hr/ml	Day 14	No
Secondary	HIV Viral Load in Breast Milk and Plasma	Positive HIV RNA in breast milk and plasma- LDL 40 copies/ml	Day 5	No
Secondary	HIV Viral Load in Breast Milk and Plasma	Positive HIV RNA in breast milk and plasma- LDL 40 copies/ml	Day 14	No