Tshireletso: Safety, Efficacy and Feasibility of Cabotegravir-LA PrEP in a Breastfeeding Population in Botswana

NCT05986084 | Active Not Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: 2023P0004155R01HD108047
• Study Type: interventional
• Target: 500
• Locations: 2 countries
• Sites: 2

Brief Summary

The goal of this this hybrid safety/implementation study is to evaluate whether using long-acting cabotegravir (CAB-LA) for HIV prevention (PrEP) is acceptable, feasible and safe in post-partum people who are breastfeeding. The main question\[s\] it aims to answer are:

• Will CAB-LA injections work well as a way to prevent HIV infection in post-partum people?
• Will CAB-LA injections be safe in post-partum people and their infants who will be breastfeeding? Participants without HIV who are admitted to the maternity ward after having delivered a baby will be offered to start CAB-LA PrEP. Those who choose to participate will receive their first dose (injection) at the maternity ward and their follow up doses (injections) at their local clinic when they come for routine post-partum and pediatric care. Participants and their infants will be followed in the study for 24 months. We will be following how many people come on-time for their CAB-LA injections, how often they keep coming back, and the reasons they continue (or stop) these injections. We will also test people for HIV at all of their visits to see how many people get HIV during the study. We will also measure the levels of the medication in the blood of the post-partum people and their infants (who may be getting some of the CAB-LA in breastmilk) and evaluate to see if their is any impact of CAB-LA on the health of the post-partum person or their infants.

Conditions

Pre-Exposure Prophylaxis (PrEP); Breast Feeding

Keywords

Botswana; Lactation; Infant PK; long acting injectable; HIV prevention; post-partum; integrase strand transfer inhibitor; cabotegravir

Outcome Measures

Primary Outcomes (6)

• Persistence of CAB-LA injections

  The % of participants continuing CAB-LA PrEP at 5 months,11 months,17 months and 24 months

  24 months

• Uptake of CAB-LA injections

  The % of eligible participants accepting CAB-LA PrEP

  24 months

• Adherence to CAB-LA injections

  The % of injection visits attended by participants

  24 months

• HIV Incidence

  The incidence of HIV infections will be calculated as the number of HIV infections infections identified during follow up, per person-year)

  24 months

• Composite Maternal Adverse Effects

  The % of participants with any of the following: grade 2 or higher DAIDS-graded adverse event, obesity (24 month BMI \>30), new onset diabetes and pre-diabetes (HgBA1c \>5.8 or diagnosis during routine care), hypertension (systolic \>140 or diastolic \>90 on 2 separate measurements, or diagnosis during routine care) and prevalence of depression (PHQ-9 score \>9) or diagnosis during routine care

  24 months

• Composite Infant Adverse Effects

  The % of infants with any of the following: incident pediatric HIV infections, Z-score \>=2 standard deviations (SD) below norms for length-for-age, weight-for-age or head-circumference-for-age based on WHO growth curves at 24 months

  24 months

Secondary Outcomes (11)

• Maternal Cabotegravir Levels

  5 months

• Infant Cabotegravir Levels

  5 months

• Median maternal weight change

  24 months

• Maternal Obesity

  24 months

• Maternal Diabetes

  24 months

Study Arms (1)

CAB-LA PrEP

EXPERIMENTAL

Following a negative HIV test, long-acting Cabotegravir Injection (CAB-LA) 600mg will be administered as a 3mL intramuscular (IM) injection in the gluteal muscle at enrollment, 1 month, and then every 2 months, for a maximum of 13 injections over 24 months of follow up.

Drug: Cabotegravir Injection [Apretude]

Interventions

Cabotegravir Injection [Apretude] DRUG

Injection

CAB-LA PrEP

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Mother 18 years of age or older and willing and able to provide an informed consent
• \< 14 days after delivery (calendar day of birth = day 0)
• Negative HIV screening test (conducted at the time of enrollment)
• Mother \<30 years old or has had \< 3 prior pregnancies (Gravida 1, 2, or 3 including this pregnancy)
• Plan to stay and receive postpartum and pediatric care in the Gaborone or Molepolole region for 24 months

You may not qualify if:

• Receiving carbemazapine, phenobarbital, phenytoin, oxycarbazepine, rifampin, rifabutin, rifapentine, systemic dexamethasone (\>1 dose oral/IV), or St. John's wort
• Suspected to have, recently diagnosed with, or on treatment for TB (due to interaction with rifampin)
• Previous hypersensitivity reaction to CAB or other INSTI
• Unstable medical or psychiatric condition making it unlikely they will be able to adhere to injections every 8 weeks
• Plan for pediatric and post-partum care outside the government system (private clinics)
• Inflammatory skin condition that compromises the safety of the intramuscular injection
• Weight \<35kg

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• Botswana Harvard AIDS Institute Partnership: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• ViiV Healthcare: collaborator

Study Sites (2)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Botswana Harvard AIDS Institute Partnership

Gaborone, Botswana

Location

MeSH Terms

Conditions

Breast Feeding

Interventions

cabotegravir

Condition Hierarchy (Ancestors)

Feeding Behavior; Behavior

Study Officials

• Rebecca Zash, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: July 27, 2023
• First Posted: August 14, 2023
• Study Start: November 30, 2023
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): November 30, 2027
• Last Updated: March 4, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will be available starting 3 months after the publication of the main outcomes of the Tshireletso study and be available until the end of the funding period for this study.

Locations

BO (1); US (1)