Cabotegravir + Rilpivirine Injections for HIV/AIDS

Not currently recruiting at 139 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: ViiV Healthcare

Must be taking: Antiretrovirals

Must not be taking: Anticoagulants, Etravirine

Disqualifiers: Pregnancy, Hepatitis B, Seizures, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if individuals with HIV-1, who currently control their virus with standard treatment, can maintain that control using monthly injections of two drugs: cabotegravir and rilpivirine, both antiretroviral medications. The study will compare the effectiveness of these injections to participants' existing daily treatment. Individuals who have controlled their HIV with current medication for at least six months and have not experienced recent treatment failure may be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it involves switching from your current HIV treatment to a new regimen of cabotegravir and rilpivirine injections. You may need to stop your current antiretroviral therapy if you are selected to switch to the new treatment.

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

Research has shown that cabotegravir and rilpivirine injections are generally well-tolerated for treating HIV. A study comparing these long-lasting injections to standard daily pills found them safe and effective. Most participants did not experience serious side effects. The most common side effect was pain at the injection site, typically mild to moderate.

Long-term research from another study confirmed the safety of these injections when administered every four to eight weeks. The FDA has also approved cabotegravir for preventing HIV in people at risk, further supporting its safety. Overall, evidence suggests these injections are a safe option for people with HIV who wish to switch from daily pills to less frequent treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard oral antiretroviral therapies for HIV, Cabotegravir and Rilpivirine are administered as long-acting injections. This treatment is unique because it offers a monthly dosing schedule compared to the daily pill regimen, which can significantly improve adherence and convenience for patients. Researchers are excited about this option as it could reduce the burden of daily medication and enhance the quality of life for those living with HIV, while maintaining effective viral suppression.

What evidence suggests that this trial's treatments could be effective for HIV?

Research shows that cabotegravir and rilpivirine injections help control the HIV-1 virus. Studies found that 97.7% of people maintained control of the virus after 24 months. In this trial, some participants will receive these injections once a month, which work as effectively as daily HIV pills. Patients have reported that this treatment is not only effective but also easier to manage than daily pills. Because the treatment lasts longer, it can improve adherence to the treatment plan. ^{6 7 8 9 10}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

ViiV Healthcare

Are You a Good Fit for This Trial?

Adults over 18 with HIV-1 who've been on a stable antiretroviral regimen for at least 6 months, showing viral suppression. They must not be pregnant or breastfeeding and agree to use effective contraception. Excluded are those with certain medical conditions, history of specific drug use, or participation in other trials.

Inclusion Criteria

I have been on my current HIV medication for at least 6 months without changing it due to treatment failure.

My HIV treatment regimen has been stable before screening.

Documented evidence of at least two plasma HIV-1 RNA measurements <50 c/mL in the 12 months prior to Screening

Exclusion Criteria

I need long-term blood thinners, with some exceptions.

I am not currently taking any medications or have a treatment history that would exclude me.

My HIV viral load has been mostly under control, with one or two increases.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral CAB 30 mg + RPV 25 mg once daily for 4 weeks, followed by monthly CAB LA + RPV LA injections

52 weeks

Monthly visits for injections

Extension

Participants who continued their current ART regimen have the option to switch to CAB LA + RPV LA injections

4 weeks oral therapy followed by injections

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cabotegravir
• Rilpivirine

Trial Overview The trial tests if switching from current antiretrovirals to long-acting injections of Cabotegravir and Rilpivirine maintains virus suppression. Participants will either continue their current treatment or switch after an initial oral phase, comparing the efficacy of both methods.

How Is the Trial Designed?

Group I: CAB LA + RPV LA every 4 weeks Experimental Treatment 4 Interventions

Eligible subjects receive Oral CAB 30 mg + RPV 25 mg once daily for four weeks, IM CAB LA 600 mg and RPV LA 900 mg for the first injection, and Week 4 onwards subjects will receive CAB LA (400 mg) + RPV LA (600 mg) injections every 4 weeks until withdrawal.

Group II: Current antiretroviral regimen Active Control 1 Intervention

Eligible subjects will continue their current anti-retroviral regimen (2 NRTIs plus an INI, NNRTI, or a PI) for 52 weeks. After 52 weeks subjects have the option to continue study participation by switching to CAB LA + RPV LA in the Extension Phase where they will follow the procedure of CAB LA + RPV LA arm.

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?

ViiV Healthcare

Lead 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

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Janssen Pharmaceuticals

Industry Sponsor

Trials

87

Recruited

208,000+

Joaquin Duato

Janssen Pharmaceuticals

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Pharmaceuticals

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

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]

In a study of 321 adults with HIV receiving the CAB + RPV LA injectable regimen, 90% of continuation injections were administered on time, indicating strong adherence to the injection schedule.

Among those who started with a viral load < 50 copies/mL, 95% remained undetectable and 99% were suppressed at their last measurement, demonstrating the high efficacy of CAB + RPV LA in maintaining virologic control in routine clinical care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabotegravir + Rilpivirine Long-Acting Injections for HIV Treatment in the US: Real World Data from the OPERA Cohort. Sension, MG., Brunet, L., Hsu, RK., et al.[2023]

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 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]

Long-acting injectable cabotegravir-rilpivirine (CAB-RPV) significantly improves viral suppression rates in people with HIV who have adherence challenges, achieving 60% suppression at 3 months compared to only 13% with standard oral treatment.

In a model projecting outcomes over 3 years, CAB-RPV combined with supportive services is expected to lead to a 44% viral suppression rate and a life expectancy of 9.4 years, outperforming both standard oral treatments and those with additional support services.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Projected Benefits of Long-Acting Antiretroviral Therapy in Nonsuppressed People With Human Immunodeficiency Virus Experiencing Adherence Barriers. Chen, W., Gandhi, M., Sax, PE., et al.[2023]

Citations

1. viivhealthcare.com viivhealthcare.com/hiv-news-and-media/news/press-releases/2025/july/daily-pills-after-achieving-rapid-viral-suppression/

ViiV Healthcare data show 89% of treatment-naïve people ... 97.7% of participants maintained virologic suppression at last known viral load at Month 24 or at discontinuation. In Europe, the COMBINE-2 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12339819/

Long-Term Real-World Use of Cabotegravir/Rilpivirine Among participants treated in-label, 84% (1417/1690) of injections were administered on time. However, 82% of all participants (80/97) ...

3. viivhealthcare.com viivhealthcare.com/hiv-news-and-media/news/press-releases/2025/july/long-acting-injectables-for-hiv-at-ias-2025/

ViiV Healthcare presents new data demonstrating positive ... 24-month outcomes of cabotegravir+rilpivirine long-acting every 2 months in a real‑world setting: effectiveness, adherence to injections, and ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40604367/

Patient-reported outcomes in clinical trials assessing the ... Results: Findings reveal that CAB + RPV-LA maintains high levels of viral suppression comparable to daily ART while improving patient ...

5. viivexchange.com viivexchange.com/content/dam/cf-viiv/viivexchange/medical/pdf/aids-2024-jonsson-oldenb%C3%BCttel-carlos-12m-clin-effect-tupeb095-final-disc.pdf

12-Month Outcomes of Cabotegravir Plus Rilpivirine Long- ... a Real-World Setting: Effectiveness, Adherence to Injections, and Patient-Reported. Outcomes From People With HIV-1 in the German CARLOS Study.

6. gskpro.com gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Vocabria/pdf/VOCABRIA-PI-PIL.PDF

VOCABRIA (cabotegravir) tablets, for oral use Clinical Trials Experience in Adolescents: In adolescents receiving VOCABRIA for HIV-1 PrEP, the safety data were comparable to the safety data reported in ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11213970/

Safety and pharmacokinetics of oral and long-acting ... Study data support using CAB-LA or RPV-LA, given every 4 or 8 weeks, per the adult-dosing regimens, in virologically suppressed adolescents ≥12 ...

8. viivhealthcare.com viivhealthcare.com/en-us/media-center/news/press-releases/2021/march/viiv-healthcare-presents-data-for-long-acting-cabotegravir-and-rilpivirine/

ViiV Healthcare presents data for long-acting cabotegravir ... Long-term efficacy and safety data from the phase IIIb ATLAS-2M study reinforce the therapeutic potential of long-acting cabotegravir and rilpivirine.

9. academic.oup.com academic.oup.com/jac/article/80/3/624/7945415

Safety and efficacy of long-acting cabotegravir/rilpivirine ... This systematic review and meta-analysis compare the safety and efficacy of LAA versus standard oral treatment (SOT) for HIV.

10. 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 Long-acting CAB and rilpivirine (RPV) (LA CAB/RPV) is FDA approved for HIV treatment. CAB-LA is FDA approved for HIV pre-exposure prophylaxis (PrEP). Human ...