Clinical trial NCT01625169: Etravirine Pharmacokinetics and HIV Viral Load in Breast Milk and Plasma
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV
Keywords: Pharmacokinetics
HIV
Breast milk
Lead sponsor: University of Southern California
Sponsor class: OTHER
Collaborators: name: Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
First posted: 2012-06-21
Enrollment: 9
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP

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.


Eligibility 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

Primary outcomes:
measure: Peak Plasma Concentration of Etravirine in Plasma
timeFrame: Day 5
measure: Peak Concentration of Etravirine in Breast Milk
timeFrame: day 5
measure: Peak Concentration of Etravirine in Breast Milk
timeFrame: day 14
measure: Peak Plasma Concentration of Etravirine in Plasma
timeFrame: day 14
measure: Area Under the Curve (AUC) 0-12 for Plasma
timeFrame: Day 5: 0, 2,4, 8 and 24 hours post dose
measure: Area Under the Curve (AUC) 0-12 for Plasma
timeFrame: Day 14: 0, 2,4, 8 and 24 hours post dose
measure: Area Under the Curve (AUC) 0-12 for Breast Milk
timeFrame: Day 5
measure: Area Under the Curve (AUC) 0-12 for Breast Milk
timeFrame: Day 14
Secondary outcomes:
measure: HIV Viral Load in Breast Milk and Plasma
timeFrame: Day 5
measure: HIV Viral Load in Breast Milk and Plasma
timeFrame: Day 14
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: LAC+USC MCA Clinic
state: California
Study officials:
affiliation: University of Southern California
name: LaShonda Y Spencer, MD
role: PRINCIPAL_INVESTIGATOR
References: