HIV
Conditions
Keywords
Pharmacokinetics, HIV, Breast milk
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.
Interventions
DRUGEtravirine 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.
Sponsors
Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
University of Southern California
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak Plasma Concentration of Etravirine in Plasma | Day 5 | Cmax ng/ml Note: One participant did not complete the Day 5 evaluation. |
| Peak Concentration of Etravirine in Breast Milk | day 5 | Cmax ng/ml Note: One participant did not complete the Day 5 evaluation. |
| Area Under the Curve (AUC) 0-12 for Plasma | Day 5: 0, 2,4, 8 and 24 hours post dose | AUC 0-12 ng\*hr/ml |
| Area Under the Curve (AUC) 0-12 for Breast Milk | Day 5 | AUC 0-12 ng\*hr/ml |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HIV Viral Load in Breast Milk and Plasma | Day 5 | Positive HIV RNA in breast milk and plasma- LDL 40 copies/ml |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HIV + Pregnant Women Etravirine PK on days 5 and 14
Etravirine pharmacokinetics in breast milk and plasma: HIV+ pregnant women will receive etravirine for 14 days postpartum. PK will be done on postpartum days 5 and 14.
There is only one arm- all pregnant women enrolled into the study will receive Etravirine 200mg PO bid for 14 days postpartum | 9 |
| Total | 9 |
Baseline characteristics
| Characteristic | HIV + Pregnant Women |
|---|---|
| Absolute CD4 at Delivery | 437 cells/ml |
| Age, Continuous | 28.1 years |
| Previous Breast Feeding No | 7 participants |
| Previous Breast Feeding Yes | 1 participants |
| Previous Pregnancies Abortion | 1 pregnancies |
| Previous Pregnancies Gravida | 3 pregnancies |
| Previous Pregnancies Parity | 2 pregnancies |
| Region of Enrollment United States | 9 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 0 Participants |
| Timing of Delivery Preterm | 1 number participants |
| Timing of Delivery Term | 8 number participants |
| Type of Delivery C-section | 2 participants |
| Type of Delivery Vaginal | 7 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 9 |
| serious Total, serious adverse events | 0 / 9 |
Outcome results
Primary
Area Under the Curve (AUC) 0-12 for Breast Milk
AUC 0-12 ng\*hr/ml
Time frame: Day 5
Population: One participant did not complete D5 visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HIV + Pregnant Women | Area Under the Curve (AUC) 0-12 for Breast Milk | 4371.9 ng*hr/ml | Standard Deviation 3491.8 |
Primary
Area Under the Curve (AUC) 0-12 for Breast Milk
AUC 0-12 ng\*hr/ml
Time frame: Day 14
Population: One participant did not complete D14 visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HIV + Pregnant Women | Area Under the Curve (AUC) 0-12 for Breast Milk | 12953.7 ng*hr/ml | Standard Deviation 10200.4 |
Primary
Area Under the Curve (AUC) 0-12 for Plasma
AUC 0-12 ng\*hr/ml
Time frame: Day 5: 0, 2,4, 8 and 24 hours post dose
Population: One participant did not complete Day 5 visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HIV + Pregnant Women | Area Under the Curve (AUC) 0-12 for Plasma | 3622.1 ng*hr/ml | Standard Deviation 2020.3 |
Primary
Area Under the Curve (AUC) 0-12 for Plasma
AUC 0-12 ng\*hr/ml
Time frame: Day 14: 0, 2,4, 8 and 24 hours post dose
Population: One participant did not complete D14 visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HIV + Pregnant Women | Area Under the Curve (AUC) 0-12 for Plasma | 4096 ng*hr/ml | Standard Deviation 2999.63 |
Primary
Peak Concentration of Etravirine in Breast Milk
Cmax ng/mL
Time frame: day 14
Population: Note: One participant did not complete the Day 14 evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HIV + Pregnant Women | Peak Concentration of Etravirine in Breast Milk | 1805.4 ng/ml | Standard Deviation 1390 |
Primary
Peak Concentration of Etravirine in Breast Milk
Cmax ng/ml Note: One participant did not complete the Day 5 evaluation.
Time frame: day 5
Population: Note: One participant did not complete the Day 5 evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HIV + Pregnant Women | Peak Concentration of Etravirine in Breast Milk | 685.4 ng/ml | Standard Deviation 477.7 |
Primary
Peak Plasma Concentration of Etravirine in Plasma
Cmax ng/ml Note: One participant did not complete the Day 5 evaluation.
Time frame: Day 5
Population: Note: One participant did not complete the Day 5 evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HIV + Pregnant Women | Peak Plasma Concentration of Etravirine in Plasma | 497.6 ng/ml | Standard Deviation 261.77 |
Primary
Peak Plasma Concentration of Etravirine in Plasma
Cmax ng/mL
Time frame: day 14
Population: Note: One participant did not complete the Day 14 evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HIV + Pregnant Women | Peak Plasma Concentration of Etravirine in Plasma | 564.6 ng/ml | Standard Deviation 412.86 |
Secondary
HIV Viral Load in Breast Milk and Plasma
Positive HIV RNA in breast milk and plasma- LDL 40 copies/ml
Time frame: Day 5
Population: One participant did not complete Visit D5.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HIV + Pregnant Women | HIV Viral Load in Breast Milk and Plasma | Breast milk | 0 participants |
| HIV + Pregnant Women | HIV Viral Load in Breast Milk and Plasma | Plasma | 1 participants |
Secondary
HIV Viral Load in Breast Milk and Plasma
Positive HIV RNA in breast milk and plasma- LDL 40 copies/ml
Time frame: Day 14
Population: One participant did not complete D14 visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HIV + Pregnant Women | HIV Viral Load in Breast Milk and Plasma | Breast milk | 2 participants |
| HIV + Pregnant Women | HIV Viral Load in Breast Milk and Plasma | Plasma | 0 participants |