Etravirine Pharmacokinetics and HIV Viral Load in Breast Milk and Plasma

Study Overview
=================
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.

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

Conditions
-----------------
HIV

Intervention / Treatment
-----------------
* Drug: Etravirine pharmacokinetics in breast milk and plasma


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: HIV+ pregnant women on HAART for the prevention of MTCT w/ undetectable viral load at time of delivery (w/i 30 days of delivery). 18 years and older Only women who are deemed by the physician as being capable of understanding that HIV positive women should not breastfeed will be approached. Life expectancy greater than 6 months No known allergies to etravirine Willingness of subject to adhere to protocol requirements. Exclusion Criteria: Pregnant women with medical or psychological contraindications to breast milk expression. 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: HIV + pregnant women<br>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<br>* HIV+ pregnant women will receive etravirine 200mg PO BID for 14 days postpartum. PK will be done on postpartum days 5 and 14.<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pharmacokinetics, HIV, Breast milk