IMPAACT 2040

IMPAACT 2040 is a Phase I/II study of the pharmacokinetics (PK) and safety of long-acting injectable cabotegravir and rilpivirine (CAB LA + RPV LA) in people with virally suppressed HIV-1 during pregnancy and postpartum. The CREATE (Cabotegravir & Rilpivirine Antiretroviral Therapy in Pregnancy) study will enroll up to 45 pregnant women and their infants. The study will enroll “Switch Group” and “Continuation Group” participants.

• The Switch Group will be on oral ART and then switched to intramuscular (IM) CAB LA + RPV LA upon entry into the study
• The continuation group will be on CAB LA + RPV LA and continue with IM dosing throughout study participation

The study includes two cohorts:

• Cohort 1 will enroll Switch Group participants who will receive CAB LA + RPV LA every four weeks (Q4W), as well as Continuation Group participants who will receive CAB LA + RPV LA either Q4W or every eight weeks (Q8W), depending on their injection schedule prior to entry. Cohort 1 will open to accrual first.
• Cohort 2 will enroll Switch Group participants who will receive CAB LA + RPV LA Q8W. Recruitment into Cohort 2 will open if there are acceptable PK, safety, and virologic outcomes from the interim analysis with data from 10 evaluable Q4W Cohort 1 Switch Group participants through six weeks postpartum.

Participants and their infants will be followed for up to six weeks or ten weeks postpartum, based on whether they are on the Q4W or Q8W schedule, to evaluate postpartum outcomes and neonatal safety of the regimen.

Site selection was completed in November 2022. IMPAACT sites located in the US and South Africa were invited to participate. US sites were invited based on availability of the recruitment population (pregnant individuals continuing on CAB LA + RPV LA). Sites in South Africa were invited to participate based on the pharmaceutical partner's assessment of anticipated timelines for regulatory review and, if applicable, addition of CAB LA + RPV LA to national guidelines.