Cabotegravir + Rilpivirine for HIV During Pregnancy

No longer recruiting at 8 trial locations

Overseen By Rachel Scheckter

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must be taking: Antiretrovirals

Must not be taking: Nevirapine, Anticoagulants

Disqualifiers: Hepatitis B, Hepatitis C, Tuberculosis, others

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

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

Compensation: Varies

Number of Visits: 4

Duration: Throughout pregnancy

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests long-acting injections of Cabotegravir and Rilpivirine for pregnant individuals living with HIV. The research aims to understand how these medications behave in the body and assess their safety during pregnancy and after birth. Participants will have HIV-1 viral suppression and may switch from oral therapy to injections or continue their current injectable regimen. Suitable candidates are those who are pregnant, have been living with HIV, and are maintaining low virus levels with their treatment. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in HIV care during pregnancy.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, it mentions that participants should not have taken any prohibited medication within seven days prior to entry, except for antiviral agents that are part of their current HIV treatment. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the long-acting injectable drugs Cabotegravir and Rilpivirine are generally well-tolerated by pregnant individuals with HIV. In past studies, the rate of negative outcomes during pregnancy, such as side effects, ranged from 26% to 35% across different groups. This indicates that these treatments do not significantly increase the risk of negative outcomes during pregnancy.

In a study of 11 live births where the mothers took these drugs at conception, only one baby was born with a birth defect, suggesting that major birth defects are rare. However, current guidelines do not recommend starting these drugs during pregnancy due to insufficient safety data.

Additionally, other studies have shown that people using these treatments long-term have successfully kept the virus under control. These findings offer some reassurance about the safety of Cabotegravir and Rilpivirine during pregnancy, but more research is needed to fully understand their effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Cabotegravir (CAB) and Rilpivirine (RPV) for treating HIV during pregnancy because they offer a novel long-acting injectable option. Unlike the standard daily oral antiretroviral therapies, these treatments are administered every four or eight weeks, potentially improving adherence and quality of life for pregnant individuals. The long-acting formulation helps maintain viral suppression with less frequent dosing, which is particularly beneficial in pregnancy when adherence to daily medication can be challenging. This approach could transform HIV management during pregnancy by offering a more convenient and consistent treatment option.

What evidence suggests that Cabotegravir & Rilpivirine might be an effective treatment for HIV during pregnancy?

Research shows that Cabotegravir (CAB) and Rilpivirine (RPV), when used together as long-acting injections, may effectively treat HIV-1. Studies have documented 25 pregnancies where individuals were exposed to CAB and RPV at conception, with some positive outcomes. Those who used these medications during pregnancy demonstrated good control of the virus. In this trial, participants will join different treatment arms, including switching to or continuing with either a four-week (Q4W) or eight-week (Q8W) CAB LA + RPV LA regimen. Despite these promising results, current guidelines advise caution when starting these treatments during pregnancy due to insufficient safety information. However, ongoing research remains optimistic about their potential benefits for pregnant individuals with HIV. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for pregnant individuals with HIV-1 who have managed to suppress the virus. It's open to those in any trimester and continues into the postpartum period. Participants must be on a stable antiretroviral regimen, with no plans to modify it except for participating in this study.

Inclusion Criteria

Intending to deliver at a study-associated medical facility, remain in the geographic area of the study, and attend regularly scheduled study visits

Negative hepatitis C antibody test result at screening

Has documented plasma HIV-1 RNA result less than 50 copies/mL within specified timeframes

Exclusion Criteria

Plasma HIV-1 RNA measurement greater than or equal to 200 copies/mL within specified timeframe

My seizures are not well-controlled.

Specific conditions during current or previous pregnancies

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Cabotegravir and Rilpivirine long-acting injectables every 4 or 8 weeks during pregnancy

Throughout pregnancy

Visits every 4 or 8 weeks

Postpartum Follow-up

Participants and their infants are monitored for safety and pharmacokinetics postpartum

6 months postpartum

What Are the Treatments Tested in This Trial?

Interventions

• Cabotegravir & Rilpivirine

Trial Overview The CREATE trial is testing two long-acting injectable drugs: Cabotegravir (CAB) at doses of either 400mg or 600mg, and Rilpivirine (RPV) at doses of either 900mg or 600mg. The goal is to see how these medications work and are processed by the body during pregnancy and after birth.

How Is the Trial Designed?

Group I: Q8W Switch Experimental Treatment 2 Interventions

Pregnant people between 10 0/7 and 19 4/7 weeks gestation with HIV-1 viral suppression on oral antiretroviral therapy willing to switch to an every eight week (Q8W) CAB LA + RPV LA regimen.

Group II: Q8W Continuation Experimental Treatment 2 Interventions

Pregnant people between 10 0/7 and 19 4/7 weeks gestation with HIV-1 viral suppression who were using every 8 week CAB LA + RPV LA at and since conception and are willing to continue their current CAB LA + RPV LA regimen.

Group III: Q4W Switch Experimental Treatment 4 Interventions

Pregnant people between 10 0/7 and 19 4/7 weeks gestation with HIV-1 viral suppression on oral antiretroviral therapy willing to switch to an every four week (Q4W) CAB LA + RPV LA regimen.

Group IV: Q4W Continuation Experimental Treatment 2 Interventions

Pregnant people 19 4/7 weeks gestation or less with HIV-1 viral suppression who were using every 4 week CAB LA + RPV LA at and since conception and are willing to continue their current CAB LA + RPV LA regimen.

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

In a study of 25 pregnancies involving women exposed to cabotegravir and rilpivirine (CAB + RPV), there were 10 live births, indicating that these medications can be used during conception with monitored outcomes.

The plasma levels of CAB and RPV during pregnancy were similar to those found in non-pregnant women, suggesting that the pharmacokinetics of these drugs remain stable and safe during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pregnancy outcomes and pharmacokinetics in pregnant women living with HIV exposed to long-acting cabotegravir and rilpivirine in clinical trials. Patel, P., Ford, SL., Baker, M., et al.[2023]

Long-acting cabotegravir/rilpivirine (CAB/RPV) was effective in achieving undetectable HIV RNA levels in a patient with a history of virologic failure within just two months of treatment initiation.

The case also highlights the occurrence of immune reconstitution inflammatory syndrome (IRIS) due to Mycobacterium avium-intracellulare infection after starting CAB/RPV, indicating that while the treatment is effective, it can lead to complications in patients with underlying infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Reconstitution Inflammatory Syndrome in Aids Patient After Successful Induction of Virological Suppression with Cabotegravir/Rilpivirine. Al-Handola, R., Chinnappan, J., Bakeer, M., et al.[2023]

Long-acting injectable therapies, cabotegravir (CAB) and rilpivirine (RPV), have been shown to be as effective as traditional oral antiretroviral therapy (ART) for HIV-1, maintaining efficacy over 96 weeks in clinical trials with virologically suppressed adults.

CAB has also demonstrated effectiveness as a preexposure prophylaxis (PrEP) option, significantly reducing HIV infections compared to daily oral medication, indicating its potential for broader use in HIV prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new paradigm for antiretroviral delivery: long-acting cabotegravir and rilpivirine for the treatment and prevention of HIV. Bares, SH., Scarsi, KK.[2023]

Cabotegravir and rilpivirine, as long-acting injectable therapy for HIV-1, have shown to be non-inferior to traditional oral triple-therapy in phase II and III trials, indicating their effectiveness as a treatment option.

Patients generally accept the 4-weekly or 8-weekly injections despite some experiencing injection-site reactions, but there are still important questions regarding missed doses, drug interactions, and the therapy's efficacy across different HIV-1 subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating cabotegravir/rilpivirine long-acting, injectable in the treatment of HIV infection: emerging data and therapeutic potential. Fernandez, C., van Halsema, CL.[2020]

Cabotegravir (CAB) combined with rilpivirine (RPV) is the first long-acting dual therapy approved for HIV-1 treatment, showing comparable maintenance of viral suppression over 160 weeks with low rates of virological failure.

This regimen offers a convenient alternative to daily oral therapy, as it is administered via intramuscular injections every 4 weeks, with minimal adverse effects and no negative impact on renal or bone health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabotegravir-Rilpivirine: The First Complete Long-Acting Injectable Regimen for the Treatment of HIV-1 Infection. Durham, SH., Chahine, EB.[2022]

Cabotegravir/rilpivirine (CAB/RPV) is the first complete injectable antiretroviral therapy approved for HIV treatment, offering a monthly intramuscular injection option that improves adherence compared to daily oral medications.

Clinical trials have shown CAB/RPV to achieve high rates of sustained viral suppression with a favorable safety profile, while also enhancing patient satisfaction due to its convenience and confidentiality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic review of cabotegravir/rilpivirine long-acting antiretroviral injectable and implementation considerations at an HIV specialty clinic. Howe, ZW., Norman, S., Lueken, AF., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36411596/

Pregnancy outcomes and pharmacokinetics in pregnant ... Results: As of 31 March 2021, 25 pregnancies following CAB + RPV exposure at conception were reported (five oral, 20 LA), including four who conceived during ...

2. academic.oup.com academic.oup.com/ofid/article/12/10/ofaf604/8269506

Third-Trimester HIV Viremia Treated With Long-Acting ... Current guidelines do not recommend LA CAB/RPV initiation during pregnancy due to limited pharmacokinetic (PK) and safety data. However, recent ...

3. 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 Adverse pregnancy outcome rates were similar across groups; negative outcomes were reported in 28% (55/194), 35% (24/69), and 26% (11/43) of pregnancies with ...

4. medinfo.gsk.com medinfo.gsk.com/5f95dbd7-245e-4e65-9f36-1a99e28e5bba/5b6eae45-0f01-49d5-b414-ae678fc5b1c1/5b6eae45-0f01-49d5-b414-ae678fc5b1c1_viewable_rendition__v.pdf

Cabotegravir plus Rilpivirine: Pregnancy Outcomes and ... Limited data for CAB + RPV are available from the APR. Through July 2024, 42 pregnancies of individuals exposed to CAB LA have been reported. The indication for ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12356711/

Long-Acting Injectable Antiretroviral Drugs for Pregnant ... An analysis of pregnancy outcomes following CAB and RPV-LA exposure at conception, for example, reported 10 live births, including one with a ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8644735/

885. Pregnancy Outcomes and Pharmacokinetics in ... Pregnancy outcomes in women exposed to CAB+RPV at conception are consistent with earlier findings. There was 1 reported congenital anomaly among 11 live births.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03299049

NCT03299049 | Efficacy, Safety and Tolerability Study of ... Eligible participants must have been on CAB LA + RPV LA regimen for a minimum of 152 weeks while on the ATLAS-2M study. Plasma HIV-1 RNA <50 c/mL at ...