Etravirine Pharmacokinetics and HIV Viral Load in Breast Milk and Plasma

Study Description

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Brief 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.

Condition or disease	Intervention/treatment	Phase
HIV	Drug: Etravirine pharmacokinetics in breast milk and plasma	Not Applicable

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	9 participants
Intervention Model:	Single Group Assignment
Masking:	None (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
Study Start Date :	April 2010
Actual Primary Completion Date :	December 2012
Actual Study Completion Date :	December 2012

Arms and Interventions

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Arm	Intervention/treatment
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.

Outcome Measures

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Primary Outcome Measures :

1. Peak Plasma Concentration of Etravirine in Plasma [ Time Frame: Day 5 ]

   Cmax ng/ml

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

2. Peak Concentration of Etravirine in Breast Milk [ Time Frame: day 5 ]

   Cmax ng/ml

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

3. Peak Concentration of Etravirine in Breast Milk [ Time Frame: day 14 ]
   Cmax ng/mL
4. Peak Plasma Concentration of Etravirine in Plasma [ Time Frame: day 14 ]
   Cmax ng/mL
5. Area Under the Curve (AUC) 0-12 for Plasma [ Time Frame: Day 5: 0, 2,4, 8 and 24 hours post dose ]
   AUC 0-12 ng*hr/ml
6. Area Under the Curve (AUC) 0-12 for Plasma [ Time Frame: Day 14: 0, 2,4, 8 and 24 hours post dose ]
   AUC 0-12 ng*hr/ml
7. Area Under the Curve (AUC) 0-12 for Breast Milk [ Time Frame: Day 5 ]
   AUC 0-12 ng*hr/ml
8. Area Under the Curve (AUC) 0-12 for Breast Milk [ Time Frame: Day 14 ]
   AUC 0-12 ng*hr/ml

Secondary Outcome Measures :

1. HIV Viral Load in Breast Milk and Plasma [ Time Frame: Day 5 ]
   Positive HIV RNA in breast milk and plasma- LDL 40 copies/ml
2. HIV Viral Load in Breast Milk and Plasma [ Time Frame: Day 14 ]
   Positive HIV RNA in breast milk and plasma- LDL 40 copies/ml

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes 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

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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

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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
First Posted:	June 21, 2012
Results First Posted:	August 7, 2014
Last Update Posted:	August 13, 2014
Last Verified:	August 2014

Keywords provided by LaShonda, 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; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents