Cabotegravir Injections for PrEP in Breastfeeding Individuals

(Tshireletso Trial)

Recruiting at 1 trial location

Overseen By Rebecca Zash, MD

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: Beth Israel Deaconess Medical Center

Must be taking: Cabotegravir

Must not be taking: Anticonvulsants, Rifamycins, Dexamethasone, St. John's wort

Disqualifiers: TB, Hypersensitivity, Unstable condition, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 24 months

500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether a long-acting injection called cabotegravir (CAB-LA) can prevent HIV in individuals who have recently given birth and are breastfeeding. The researchers aim to determine the injection's safety and effectiveness for both the parent and the breastfeeding infant. This study targets those with a negative HIV test who are within 14 days postpartum and plan to remain in certain regions for follow-up care. Participants will receive regular injections and check-ups over a 24-month period to monitor health and any side effects. As a Phase 4 trial, this research focuses on understanding how this already FDA-approved and effective treatment can benefit more patients.

Do I need to stop my current medications to join the trial?

You may need to stop certain medications to join the trial. Specifically, you cannot be taking carbemazapine, phenobarbital, phenytoin, oxycarbazepine, rifampin, rifabutin, rifapentine, systemic dexamethasone, or St. John's wort.

What is the safety track record for Cabotegravir injections?

Research shows that cabotegravir (CAB-LA) is under investigation for safety in breastfeeding individuals. Earlier studies suggest that CAB-LA is generally well-tolerated, with most experiencing only mild side effects, such as soreness at the injection site. Although specific safety information for breastfeeding individuals is still being collected, ongoing studies are examining this aspect.

CAB-LA has already received FDA approval for other uses, indicating its general safety. However, this later-stage study specifically assesses the long-term safety of CAB-LA for both the breastfeeding individual and their baby. The study will monitor any effects on the health of both the mother and the baby. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Cabotegravir is unique because it offers a long-acting injectable form of HIV pre-exposure prophylaxis (PrEP), which is particularly beneficial for breastfeeding individuals. Unlike the current standard oral PrEP options like Truvada or Descovy that require daily pills, cabotegravir is administered via an intramuscular injection once every two months after initial doses. This extended dosing interval can improve adherence and convenience, reducing the burden of daily medication and enhancing protection against HIV. Researchers are excited about this treatment because it represents a significant advancement in HIV prevention, potentially increasing accessibility and adherence in populations that may struggle with daily pill regimens.

What evidence suggests that cabotegravir injections could be an effective treatment for HIV prevention in breastfeeding individuals?

Research shows that cabotegravir (CAB-LA), a long-lasting injection to prevent HIV, is both effective and safe. Studies have found that over 95% of people continue with the injections without major problems. Pregnant and breastfeeding individuals tolerate the medication well, with no increased risk of birth defects. Very little of the drug passes to infants through breast milk, supporting its use. In this trial, participants will receive CAB-LA injections as a promising option for preventing HIV in breastfeeding individuals. ^{2 5 6 7 8}

Who Is on the Research Team?

Rebecca Zash, MD

Principal Investigator

Beth Israel Deaconess Medical Center

Are You a Good Fit for This Trial?

This trial is for mothers over 18, within 14 days post-delivery, HIV-negative, with fewer than three prior pregnancies. They must plan to stay in Gaborone or Molepolole regions of Botswana for two years and be willing to receive injections every eight weeks. Exclusions include TB treatment, unstable conditions affecting adherence, care outside government clinics, weight under 35kg, certain medications use or previous reactions to CAB.

Inclusion Criteria

< 14 days after delivery (calendar day of birth = day 0)

Negative HIV screening test (conducted at the time of enrollment)

I am a mother, over 18, and can consent to participate.

Exclusion Criteria

I am currently taking medication such as carbemazapine or St. John's wort.

I am able to follow a treatment plan that requires injections every 8 weeks.

Plan for pediatric and post-partum care outside the government system (private clinics)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive long-acting Cabotegravir (CAB-LA) injections for HIV prevention, starting at the maternity ward and continuing at local clinics.

24 months

1 visit at enrollment, followed by visits at 1 month and every 2 months

Follow-up

Participants and their infants are monitored for safety, adherence, and HIV incidence.

24 months

Regular visits aligned with treatment schedule

Pharmacokinetics Substudy

Evaluation of CAB-LA levels in maternal serum, breastmilk, and infant serum.

5 months

Visits at 1 month and 5 months for PK assessments

What Are the Treatments Tested in This Trial?

Interventions

• Cabotegravir

Trial Overview

The study tests the safety and effectiveness of Cabotegravir-LA injections as HIV prevention in breastfeeding post-partum individuals. Participants will get their first dose at the maternity ward followed by doses at local clinics during routine visits. The study monitors on-time injection attendance and reasons for continuation or discontinuation over a period of 24 months.

How Is the Trial Designed?

Group I: CAB-LA PrEP Experimental Treatment 1 Intervention

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.

Cabotegravir is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Vocabria for:

• HIV-1 infection

Approved in United States as Vocabria for:

• HIV-1 infection

Approved in Canada as Vocabria for:

• HIV-1 infection

Approved in Japan as Vocabria for:

• HIV-1 infection

Who Is Running the Clinical Trial?

Beth Israel Deaconess Medical Center

Lead Sponsor

Trials

872

Recruited

12,930,000+

Botswana Harvard AIDS Institute Partnership

Collaborator

Trials

14

Recruited

26,900+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

ViiV Healthcare

Industry Sponsor

Trials

379

Recruited

479,000+

Founded

2009

Headquarters

London, England, UK

Known For

HIV Research

Top Products

- Tivicay (dolutegravir), - Triumeq (abacavir/dolutegravir/lamivudine), - Juluca (dolutegravir/rilpivirine), - Apretude (cabotegravir)

Dr. Harmony Garges

ViiV Healthcare

Chief Medical Officer

MD

Deborah Waterhouse

ViiV Healthcare

Chief Executive Officer since 2017

Bachelor's degree in Business Administration

Published Research Related to This Trial

Injectable PrEP (CAB-LA) could significantly reduce HIV transmission rates among pregnant and breastfeeding women in South Africa, with estimated reductions of up to 41.2% in vertical transmission to infants compared to no PrEP.

In comparison to oral PrEP, CAB-LA shows greater efficacy in preventing new HIV infections, suggesting it may be a more effective option for this high-risk population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential benefits of long-acting injectable cabotegravir in pregnant and breastfeeding women and their infants: a modelling study. Johnson, LF., Myer, L., Jamieson, L., et al.[2023]

Cabotegravir extended-release (ER) injectable suspension is the first long-acting injectable option approved for HIV-1 pre-exposure prophylaxis (PrEP), allowing for infrequent dosing every 2 months after an initial loading period, which enhances convenience for users.

In clinical trials, cabotegravir ER demonstrated superior efficacy compared to daily oral emtricitabine/tenofovir disoproxil fumarate in preventing HIV-1 acquisition among at-risk populations, including transgender women and cisgender men who have sex with men.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabotegravir Extended-Release Injectable Suspension: A Review in HIV-1 Pre-Exposure Prophylaxis. Blair, HA.[2022]

Cabotegravir (CAB-LA) is the first long-acting injectable medication approved for HIV preexposure prophylaxis (PrEP), showing superior efficacy compared to daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in preventing HIV-1 infection among high-risk individuals, as demonstrated in two phase 3 trials that were stopped early due to its effectiveness.

While CAB-LA is generally well-tolerated, with injection site reactions being the most common side effect, it may be particularly beneficial for individuals who struggle with adherence to daily oral medications, although it is more expensive than generic options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabotegravir: The First Long-Acting Injectable for HIV Preexposure Prophylaxis. Durham, SH., Milam, A., Waer, D., et al.[2023]

A systematic review of 62 studies found that there is a general preference for injectable PrEP (specifically cabotegravir) among potential users, as it may help overcome adherence challenges associated with daily oral PrEP.

Concerns about injectable PrEP include fear of needles and logistical issues, highlighting the need for personalized options that allow users to choose the prevention method that best fits their lifestyle and preferences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review of the values and preferences regarding the use of injectable pre-exposure prophylaxis to prevent HIV acquisition. Lorenzetti, L., Dinh, N., van der Straten, A., et al.[2023]

Long-acting injectable cabotegravir (CAB LA) for HIV preexposure prophylaxis (PrEP) has shown promising results in phase 2 studies, with effective dosing at 8-week intervals that maintains target drug levels in both men and women.

CAB LA has a favorable safety profile, requiring no dose adjustments for patients with liver or kidney issues and showing minimal drug-drug interactions, making it a potentially effective alternative for individuals who struggle with daily pill adherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting injectable cabotegravir for the prevention of HIV infection. Clement, ME., Kofron, R., Landovitz, RJ.[2023]

Long-acting injectable cabotegravir (CAB-LA) could significantly reduce new HIV infections if PrEP coverage is expanded, particularly in high-incidence areas like Atlanta, where increasing coverage from 29% to 40% could avert 36% of new infections by 2032.

In contrast, achieving similar reductions in lower-incidence areas like Montreal and the Netherlands requires much larger increases in PrEP coverage, highlighting that CAB-LA's impact is more pronounced in regions with higher HIV transmission rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population-level impact of expanding PrEP coverage by offering long-acting injectable PrEP to MSM in three high-resource settings: a model comparison analysis. Stansfield, SE., Heitner, J., Mitchell, KM., et al.[2023]

Long-acting cabotegravir (CAB-LA) is a promising new option for pre-exposure prophylaxis (PrEP) that could benefit various populations, including cis-women of reproductive potential.

The unique pharmacokinetics of CAB-LA may influence how it is prescribed, potentially improving adherence and effectiveness in preventing HIV transmission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is Long-acting Cabotegravir a Pre-exposure Prophylaxis Option for Women of Childbearing Potential? Sahloff, EG., Hamons, N., Baumgartner, K., et al.[2022]

Cabotegravir (Apretude) is an effective extended-release injectable medication used as pre-exposure prophylaxis (PrEP) to significantly reduce the risk of acquiring HIV-1 in HIV-negative individuals at risk.

It is approved for use in adults and adolescents who weigh at least 35 kg (77 lb), highlighting its targeted application for those most vulnerable to sexually transmitted HIV-1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabotegravir (Apretude) for Pre-exposure Prophylaxis for HIV Type 1 Infection. El-Haddad, A., Erlich, D.[2023]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12495377/

Early results from implementation of HIV pre-exposure ...

Adherence to injections exceeded 95%, tolerability was favourable and only 1.5% discontinued for drug-related reasons. These findings ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05986084

Tshireletso: Safety, Efficacy and Feasibility of Cabotegravir- ...

The investigators will also evaluate safety outcomes, including postpartum depression, weight gain, and infant growth and INSTI resistance in incident HIV ...

3.

prepwatch.org

prepwatch.org/wp-content/uploads/2023/01/BioPIC-IS-Meeting-CAB-for-PrEP-Research-During-Pregnancy-and-Breastfeeding-Notes-Public.pdf

Coordinating Implementation Science for Cabotegravir

Results suggested that residual CAB is generally well tolerated during pregnancy and breastfeeding with no increased risk of congenital anomalies found in ...

4.

viivhealthcare.com

viivhealthcare.com/en-us/media-center/news/press-releases/2024/july/viiv-healthcare-announces-positive-new-data-for-apretude/

ViiV Healthcare announces positive new data for Apretude ...

Adverse pregnancy outcome rates were similar across groups, with 33% (70/212) using cabotegravir LA for PrEP during pregnancy, 38% (26/68) ...

5.

aidsmap.com

aidsmap.com/news/jul-2025/lenacapavir-and-cabotegravir-prep-supported-use-pregnancy-and-breastfeeding

Lenacapavir and cabotegravir PrEP supported for use in ...

Both drugs showed minimal transfer to infants through breast milk and no increase in adverse pregnancy or birth outcomes, supporting their use ...

6.

clinicalinfo.hiv.gov

clinicalinfo.hiv.gov/en/guidelines/perinatal/pre-exposure-prophylaxis-prep-prevent-hiv

Pre-exposure Prophylaxis (PrEP) to Prevent HIV During ...

If pregnancy occurs while using TDF/FTC as PrEP, PrEP use can continue throughout pregnancy and breastfeeding. Risk for HIV acquisition should ...

7.

reporter.nih.gov

reporter.nih.gov/search/66KpMDasUkSgKV1csem0Yg/project-details/10676833

Linking HIV Prevention and post-partum care

In addition to identifying strategies to efficiently reach young women at risk for HIV, breastfeeding safety data for CAB- LA are needed to achieve widespread ...

8.

clinicalinfo.hiv.gov

clinicalinfo.hiv.gov/en/guidelines/perinatal/safety-toxicity-arv-agents-integrase-inhibitors-cabotegravir-vocabria

Appendix B: Cabotegravir - Safety and Toxicity in Pregnancy

Placental and Breast Milk Passage. Studies in lactating rats and their offspring indicate that CAB is present in rat milk. See Rilpivirine for data about RPV.