HIV -1 Infection
Conditions
Keywords
HIV, Pregnancy, CAB LA + RPV LA
Brief summary
Phase IV, multi-site, open-label, non-randomized study of the pharmacokinetics (PK) of long-acting injectable cabotegravir and rilpivirine (CAB LA + RPV LA) during pregnancy and postpartum.
Detailed description
Up to 40 adult-participants with HIV viral suppression will be enrolled, in pairs with their infants, to achieve 30 evaluable adult-participants overall. The study will include women who initiated CAB LA + RPV LA outside the study, prior to study entry, either pre-conception (including on the day of conception) or post-conception.
Interventions
DRUGEvery 4-week long-acting injectable cabotegravir and rilpivirine
Long-acting injectable cabotegravir and rilpivirine, initiated pre- or post-conception. Participants will receive these drugs as prescribed outside the study by their non-study clinical care provider
Sponsors
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute of Mental Health (NIMH)
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Willing and able to provide written informed consent for study participation for self and infant * At screening, age 18 years or older * Has a viable, intrauterine, singleton pregnancy with fetal ultrasound with an estimated gestational age (EGA) between 10 0/7 and 23 6/7 weeks (inclusive) at entry * At entry, intending to deliver at a study-associated medical facility and remain in the geographic area of the study for the duration of anticipated follow-up * Was diagnosed with HIV prior to the current pregnancy * Has a documented plasma HIV RNA result less than 50 copies/mL from a specimen collected within 28 days prior to entry * Has the following laboratory test results from a specimen collected within 28 days prior to entry (1) Grade 2 or lower platelets (greater than or equal to 50,000 cells/mm3 or greater than or equal to 50.00 x 109 cells/L); (2) Grade 1 or lower ALT (less than 2.5 x upper limit of normal; (3) Grade 1 or lower aspartate aminotransferase (AST) * Received first dose of CAB LA + RPV LA prior to entry (before or after conception of the current pregnancy) and is expected to receive CAB LA + RPV LA on a Q4W schedule for the duration of study participation
Exclusion criteria
* History of treatment/virologic failure associated with documented or suspected viral resistance to CAB or RPV (including oral RPV) * Has any of the following (1) HIV Subtype A6; (2) History of hypersensitivity reaction (HSR), known or suspected allergy to drugs under study, or any other contraindication to CAB or RPV; (3) Current contraindication to IM injection such as a current inflammatory skin condition that compromises the safety of IM injections or a dermatological condition which may interfere with the interpretation of ISRs; (4) Current use or anticipated need of therapeutic anticoagulation; (5) History of known or suspected bleeding disorder; (6) Current severe hepatic impairment (Class C) as determined by Child-Pugh classification; (7) History of suicidal ideation or attempt within six months of entry; (8) History of unstable or poorly controlled seizure disorder; (9) Current tuberculosis infection; (10) Current cervical intraepithelial neoplasia (CIN) 2 or 3, or malignancy other than Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma * Has any of the following during the current pregnancy: (1) Abnormal placentation, including placenta previa (complete) and placenta accreta/increta/percreta; (2) Cervical cerclage/cervical incompetence; (3) Abnormal fetal anatomy * Had any of the following in a previous pregnancy: (1) Eclampsia/Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) syndrome; (2) Intrauterine fetal demise (EGA greater than 20 weeks) without known nonrecurrent etiology; (3) Spontaneous very preterm delivery (less than 32 weeks); (4) Very LBW (less than 1500 g); (5) Cervical or abdominal cerclage due to cervical incompetence * Receipt of any prohibited medication within seven days prior to entry * Enrolled in another clinical trial of an investigational agent, device, or vaccine that may impact the PK of CAB or RPV * Receipt of an investigational agent or chemotherapy within 30 days prior to study entry * Adult-participant or fetus has any condition, such as uncontrolled diabetes, hypertension, or other comorbidities, that, in the opinion of the site investigator, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric mean pharmacokinetic trough of CAB and RPV from every 4 week (Q4W) CAB LA and RPV LA measured every 4 weeks in plasma in second trimester, third trimester, and postpartum | Measured from study entry through six weeks postpartum | Geometric mean pharmacokinetic trough of CAB and RPV from every 4 week (Q4W) CAB LA and RPV LA measured every 4 weeks in plasma in second trimester, third trimester, and postpartum |
| Population PK: geometric mean clearance of CAB and RPV in second trimester, third trimester, and postpartum derived from a population PK model | Measured from study entry through six weeks postpartum | Population PK: geometric mean clearance of CAB and RPV in second trimester, third trimester, and postpartum derived from a population PK model |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of adult participants with HIV RNA less than 50 copies/mL at delivery | Delivery | Percentage of adult participants with HIV RNA less than 50 copies/mL at delivery |
| Percentage of adult participants with virologic escape | Measured from study entry through six weeks postpartum | Percentage of adult participants with virologic escape, defined as a single measurement of HIV RNA greater than or equal to 200 copies/mL |
| Percentage of adult participants with confirmed virologic failure | Through 6 weeks postpartum | Percentage of adult participants with confirmed virologic failure, defined as two successive HIV RNA test results greater than or equal to 200 copies/mL from separate specimens collected at least two weeks apart |
| Number of adult participants with HIV resistance to CAB or RPV who had confirmed virologic failure | Through 6 weeks postpartum | Number of adult participants with HIV resistance to CAB or RPV using IAS-USA, in participants who experienced confirmed virologic failure |
| Number of infant participants with perinatal transmission | Birth and six weeks post-birth | Number of infant participants with perinatal transmission |
| Percentage of adult participants with at least one Grade 3 or higher adverse event | Measured from study entry through six weeks postpartum | Percentage of adult participants with at least one Grade 3 or higher adverse event |
| Percentage of adult participants with at least one serious adverse event | Measured from study entry through six weeks postpartum | Percentage of adult participants with at least one serious adverse event |
| Percentage of infant participants with at least one serious adverse event | Measured from birth through six weeks post-birth | Percentage of infant participants with at least one serious adverse event |
| Percentage of adult participants with spontaneous abortion | Through 6 weeks postpartum | Percentage of adult participants with spontaneous abortion less than 20 weeks gestation |
| Percentage of adult participants with fetal demise/stillbirth | Through 6 weeks postpartum | Percentage of adult participants with fetal demise/stillbirth, at greater than or equal to 20 weeks gestation |
| Percentage of infant participants born small for gestational age | Birth | Percentage of infant participants born small for gestational age, where birthweight is less than 10th percentile for sex and gestational age assigned at birth, based on Intergrowth 21st Standards |
| Percentage of infant participants with low birth weight | Birth | Percentage of infant participants with low birth weight, defined as less than 2500 grams |
| Percentage of infant participants born preterm | Birth | Percentage of infant participants born preterm, defined as less than 37 weeks gestation |
| Percentage of infant participants with a congenital anomaly | Birth | Percentage of infant participants with a congenital anomaly based on the Metropolitan Atlanta Congenital Defects Program (MACDP) definition of defect |
| Percentage of adult participants who would recommend CAB LA and RPV LA injections for other people living with HIV during pregnancy | Six weeks postpartum | Percentage of adult participants who would recommend CAB LA and RPV LA injections |
| Percentage of infant deaths | Measured from birth through six weeks post-birth | Percentage of infant deaths |
| Percentage of mother-infant pairs with occurrence of any adverse pregnancy outcome | Through 6 weeks postpartum | Percentage of mother-infant pairs with occurrence of any adverse pregnancy outcome. Outcomes include: spontaneous abortion (\<20 weeks gestation), stillbirth (≥20 weeks gestation), preterm delivery (\<37 gestational weeks), small for gestational age (\<10th percentile per INTERGROWTH 21st Standards), or neonatal death |
Countries
United States
Contacts
CONTACTLisa Levy
STUDY_CHAIRRachel Scott, MD, MPH
MedStar Washington Hospital Center & MedStar Health Research Institute
Outcome results
None listed