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Number of Visits: Unknown

Oral vs Injectable Therapy for HIV
(VOLITION Trial)

Not currently recruiting at 68 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: ViiV Healthcare

Must not be taking: Anticoagulants, Immunomodulators, Torsade drugs

Disqualifiers: Pregnancy, Cardiovascular disease, Hepatitis B, others

No Placebo GroupAll 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 DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments for individuals with HIV-1 who haven't taken any antiretroviral therapy. Participants will begin with a daily oral pill combining dolutegravir and lamivudine (DTG/3TC) until their viral load is controlled. Once the virus is suppressed, they can either continue with the pill or switch to long-acting injections of cabotegravir and rilpivirine (CAB + RPV LA). The study aims to evaluate the effectiveness of these treatments and gather participants' feedback. It suits those diagnosed with HIV-1 who haven't started treatment. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are taking certain medications that are not allowed by the study protocol, and you must be willing to switch to an alternative if needed.

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

Research shows that both treatment options in this study are generally safe. Studies indicate that the long-acting injections of cabotegravir plus rilpivirine (CAB + RPV LA) are usually safe and well-tolerated. The most common side effects include mild reactions at the injection site, which are typically easy to manage.

Research also shows that the oral combination of dolutegravir and lamivudine (DTG/3TC) is effective and well-tolerated. Many patients starting this treatment achieved low viral levels within 48 weeks, indicating it works well and is safe for most people.

Both treatments have been tested in similar groups before, showing promising safety results. This information might help prospective participants feel more confident about the treatments being tested.¹ ² ³ ⁴ ⁵

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments CAB + RPV LA and DTG/3TC because they offer new options for managing HIV. Unlike standard antiretroviral therapies that often require daily oral pills, CAB + RPV LA is a long-acting injectable, which could mean less frequent dosing and potentially improved adherence. On the other hand, DTG/3TC is a simplified oral regimen with just two drugs, which could reduce side effects and drug interactions compared to more complex regimens. These innovations could significantly enhance the quality of life for people living with HIV.

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

Research has shown that both treatments in this trial work well for people with HIV-1. Participants in one arm will receive the oral combination of dolutegravir and lamivudine (DTG/3TC), which is highly effective, with 82% of participants having a very low viral load after 48 weeks. Studies on this treatment in individuals new to HIV therapy also show strong results, with up to 95% reducing the virus to very low levels.

In another arm, participants will receive the long-acting injectable combination of cabotegravir and rilpivirine (CAB + RPV LA), which has shown promise. It demonstrated a high success rate, with 87% of patients achieving good viral control. These findings support the potential effectiveness of both treatments in managing HIV-1.² ⁴ ⁵ ⁶ ⁷

Are You a Good Fit for This Trial?

Adults with HIV-1 who haven't taken antiretroviral therapy before can join this trial. They must have a certain level of HIV in their blood and be able to consent to the study's requirements. People with severe liver issues, heart conditions, risk of suicide, untreated syphilis or hepatitis B infection, recent exposure to experimental drugs or vaccines, or those on certain medications are excluded.

Inclusion Criteria

Participants having plasma HIV-1 RNA ≥1,000 c/mL at Screening

Participants enrolled in France must be affiliated to, or a beneficiary of, a social security category

I have never taken antiretroviral drugs before.

See 1 more

Exclusion Criteria

Participants with treatment with any of the following agents within 28 days of Screening: radiation therapy, cytotoxic chemotherapeutic agents, tuberculosis therapy with the exception of isoniazid (isonicotinylhydrazid, INH), anti-coagulation agents, with the exception of the use of low dose acetylsalicylic acid (≤325 mg), immunomodulators that alter immune responses such as chronic systemic corticosteroids, interleukins, or interferons. Note: Participants using short-term (e.g. ≤21 days) systemic corticosteroid treatment; topical, inhaled and intranasal corticosteroids are eligible for enrolment, Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening, Treatment with any agent with documented activity against HIV-1 in vitro within 28 days of first dose of study treatment. Treatment with acyclovir/valacyclovir is permitted, Use of medications which are associated with Torsade de Pointes, Participants receiving any protocol-defined prohibited medication and who are unwilling or unable to switch to an alternate medication, Any verified Grade 4 laboratory abnormality, with the exception of Grade 4 lipid abnormalities, Any acute laboratory abnormality at Screening, which, in the opinion of the Investigator, would preclude the participant's participation in an interventional clinical trial, Participant has estimated creatine clearance <30 milliliter per minute (mL/min) per 1.73 square meter (m^2) using the refitted, race-neutral Chronic Kidney Disease Epidemiology Collaboration (CKDEPIcr_R) method, Alanine aminotransferase (ALT) ≥5 times the upper limit of normal (ULN); or ALT ≥3xULN and bilirubin ≥1.5xULN (with >35 percentage (%) direct bilirubin), Participants known or suspected to have acquired HIV-1 concurrent with use of protease-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP) must be discussed with the Medical Monitor prior to enrolment, Participant has a gluteal implant/enhancements (including fillers); or tattoo or other dermatological condition overlying the gluteus region which may interfere with interpretation of injection site reactions, Any condition which, in the opinion of the Investigator, may interfere with the absorption, distribution, metabolism or excretion of the study drugs or render the participant unable to receive study drugs, Any pre-existing physical or mental condition (including substance use disorder) which, in the opinion of the Investigator, may interfere with the participant's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the participant, Participant is currently participating in, or anticipates being selected for, any other interventional study

My liver disease is stable and does not include severe symptoms or conditions.

I do not have untreated syphilis or have completed treatment for it at least 7 days ago.

See 17 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Treatment

Participants receive oral DTG/3TC once daily until virologic suppression is attained

Approximately 20 weeks

Maintenance Treatment

Participants choose to either continue oral DTG/3TC or switch to CAB + RPV LA every two months

11 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

CAB + RPV LA
DTG/3TC

Trial Overview The trial is testing two drug regimens for treating HIV-1: an oral tablet (DTG/3TC) taken daily and long-acting injectable drugs (CAB + RPV LA) given every two months. Participants start with the oral tablet and after viral suppression can choose to switch to injections or continue pills.

How Is the Trial Designed?

2Treatment groups

Experimental Treatment

Group I: Participants Receiving DTG/3TC Fixed Dose Combination (FDC)Experimental Treatment1 Intervention

Group II: Participants Receiving CAB + RPV LAExperimental Treatment2 Interventions

Find a Clinic Near You

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

Published Research Related to This Trial

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]

Long-acting injectable cabotegravir (CAB) combined with rilpivirine (RPV) is an effective maintenance therapy for HIV suppression in patients who have maintained an undetectable viral load for 3 to 6 months, providing an alternative to daily oral medications.

There is a growing interest in developing new long-acting injectable antiretroviral agents with different mechanisms of action, which are currently being tested in phase 2 and 3 clinical trials to further improve treatment options for patients unable to adhere to daily oral therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Acting Injectable Antiretroviral Agents for HIV Treatment and Prevention.Kim, YS.[2022]

Citations

1.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/40204512/

Efficacy of long-acting cabotegravir plus rilpivirine in ...The cumulative probability of achieving virologic success was 87% (79%-95%). Most patients maintained adherence rates above 90% to their scheduled injection ...

2.academic.oup.comacademic.oup.com/ofid/article/12/5/ofaf220/8116433

Clinical Outcomes and Perspectives of People With Human ...Participants receiving long-acting cabotegravir plus rilpivirine experienced high rates of virologic suppression and a low rate of ...

3.viivhealthcare.comviivhealthcare.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.sciencedirect.comsciencedirect.com/science/article/pii/S1341321X2500131X

Efficacy and safety of switching to long-acting cabotegravir ...Mean (SD) HIVTSQs treatment satisfaction scores of Japanese participants showed greater improvement from baseline to Month 12 in the CAB+RPV LA group (+6.25 [ ...

5.viivexchange.comviivexchange.com/content/dam/cf-viiv/viivexchange/medical/pdf/aids-2024-pozniak-combine-util-and-adher-tupec278-disc.pdf

Real-World Utilization and Effectiveness of Long-Acting ...Three individuals (0.8%) had confirmed virologic failure (CVF) after initiation of CAB+RPV LA. Real-World Utilization and Effectiveness of Long-Acting ...

6.pmc.ncbi.nlm.nih.govpmc.ncbi.nlm.nih.gov/articles/PMC12339819/

Long-Term Real-World Use of Cabotegravir/RilpivirineDespite increasing use of LA-CAB/RPV, long-term real-world data on durability, adherence, and virological outcomes remain limited to 2 years.

7.pmc.ncbi.nlm.nih.govpmc.ncbi.nlm.nih.gov/articles/PMC12390647/

Safety, Tolerability, and Metabolic Effects of Long-Acting ...Clinical trial data suggest that LA CAB/RPV is generally safe and well tolerated. The most common side effects were injection site reactions, ...

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