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

Trial Summary

What is the purpose of this trial?

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.

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 data supports the effectiveness of the drug Cabotegravir for PrEP in breastfeeding individuals?

Cabotegravir, a long-acting injectable drug, has been shown to be more effective than daily oral PrEP in preventing HIV in various populations, including transgender women, men who have sex with men, and cisgender women. Its long-lasting formulation allows for less frequent dosing, making it a convenient option for those at risk of HIV. ^{1 2 3 4 5}

Is cabotegravir safe for humans?

Cabotegravir, used as a long-acting injection for HIV prevention, has been generally well tolerated in clinical trials, though more long-term safety data is needed. It has been approved for use in adults and adolescents at risk of HIV, showing it is considered safe for these groups. ^{3 4 5 6 7}

How is the drug Cabotegravir unique for HIV prevention in breastfeeding individuals?

Cabotegravir is unique because it is a long-acting injectable drug that requires less frequent dosing compared to daily oral medications, making it more convenient for users. It is the first long-acting injectable approved for HIV prevention, offering an alternative to daily pills, and is particularly beneficial for breastfeeding individuals who may find daily medication challenging. ^{2 3 4 7 8}

Research Team

Rebecca Zash, MD

Principal Investigator

Beth Israel Deaconess Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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 (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]

References

1. Switzerland 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. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Systematic review of the values and preferences regarding the use of injectable pre-exposure prophylaxis to prevent HIV acquisition. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

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

4. United States pubmed.ncbi.nlm.nih.gov

Is Long-acting Cabotegravir a Pre-exposure Prophylaxis Option for Women of Childbearing Potential? [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Long-acting injectable cabotegravir for the prevention of HIV infection. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Cabotegravir: The First Long-Acting Injectable for HIV Preexposure Prophylaxis. [2023]

7. England pubmed.ncbi.nlm.nih.gov

The potential benefits of long-acting injectable cabotegravir in pregnant and breastfeeding women and their infants: a modelling study. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Cabotegravir (Apretude) for Pre-exposure Prophylaxis for HIV Type 1 Infection. [2023]