Long-Acting Antiretroviral Therapy for HIV

Not currently recruiting at 34 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

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

Must be taking: Antiretrovirals

Disqualifiers: Pregnancy, Seizures, Liver disease, 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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of two different HIV treatments for individuals who have struggled with medication adherence. One group will receive a long-acting treatment with fewer doses, while the other will continue with daily pills. The study will assess the effectiveness and safety of these treatments in controlling the virus. It is suitable for individuals with HIV who have faced challenges in adhering to their medication and have a viral load above a certain level. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you must not require any medication that is prohibited with the study medication, so it's best to discuss your current 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 combination of CAB-LA (cabotegravir) and RPV-LA (rilpivirine) is safe for people living with HIV. Studies have found that these long-acting treatments often lead to good results with few serious side effects. For example, a review found that this combination is as safe as standard HIV pills.

Other research highlights that these injections improve adherence to treatment plans, which is crucial for controlling the virus. Adults generally tolerate the doses well, with side effects usually mild or moderate. These may include pain at the injection site or headaches, though they are uncommon.

Overall, the safety data for CAB-LA and RPV-LA appears promising. These treatments offer a reliable option for those seeking alternatives to daily pills. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about long-acting antiretroviral therapy (LA ART) for HIV because it offers a new delivery method that could significantly improve patient experience and adherence. Unlike the standard of care, which typically involves daily oral medications, LA ART uses injectable forms of cabotegravir (CAB) and rilpivirine (RPV) that are administered once every four weeks. This long-acting approach can reduce the burden of daily pill-taking and might help people stick to their treatment plan better. By offering a less frequent dosing schedule, LA ART has the potential to enhance convenience and improve outcomes for individuals living with HIV.

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

Research shows that long-acting cabotegravir (CAB-LA) and rilpivirine (RPV-LA) effectively treat HIV. In this trial, participants in one arm will receive this combination, which studies have shown helps many patients control the virus. Specifically, one study found that about 87% of participants successfully managed the virus, keeping it well-controlled. Most participants adhered closely to their treatment plan, with over 90% maintaining their schedule, which is crucial for the treatment's effectiveness. Overall, this long-acting treatment has proven to be a strong option for managing HIV. ^{5 6 7 8 9}

Who Is on the Research Team?

Aadia Rana, M.D.

Principal Investigator

Alabama CTU

Are You a Good Fit for This Trial?

This trial is for adults with HIV who've struggled to stick to their oral ART medication. They must have a recent history of poor viral control or missed clinic visits, no resistance to certain HIV drugs, and acceptable blood test results. Pregnant or breastfeeding individuals, those with allergies to study drugs, chronic hepatitis C requiring treatment during the study, active hepatitis B infection, or conditions affecting drug injections are excluded.

Inclusion Criteria

Laboratory values within specified ranges

HIV-1 infection confirmed by licensed tests

Agreement to use contraception for participants of reproductive potential

Exclusion Criteria

I have chronic Hepatitis C and plan to start treatment.

I need long-term blood thinner medication.

QTc greater than 450 ms within 60 days prior to study entry

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive a SOC oral ART regimen with conditional economic incentives for up to 24 weeks

24 weeks

Regular visits for monitoring and incentives

Randomization and Treatment

Participants are randomized to either LA ART or SOC. LA ART involves oral RPV + CAB for 4 weeks (optional) followed by RPV-LA + CAB-LA every 4 weeks. SOC continues for 52 weeks.

52 weeks

Monthly visits for LA ART injections or regular visits for SOC monitoring

Continuation/Crossover

Participants on LA ART continue for 52 weeks. SOC participants may cross over to LA ART if criteria are met.

52 weeks

Monthly visits for LA ART injections

Observation

Participants are followed on locally sourced oral ART for up to 52 weeks. Option to restart LA ART if available.

52 weeks

Regular follow-up visits

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CAB-LA Loading Dose
• CAB-LA Maintenance Dose
• Oral CAB
• Oral RPV
• RPV-LA Loading Dose
• RPV-LA Maintenance Dose
• Standard of Care (SOC) Oral ART

Trial Overview The LATITUDE Study is testing long-acting antiretroviral therapy (LA ART) against standard oral ART in people with HIV who have trouble taking daily pills. It aims to see if LA injections can better manage their condition by comparing effectiveness and safety over time.

How Is the Trial Designed?

Group I: Step 2 Arm A: LA ART Experimental Treatment 6 Interventions

In Step 2, participants received oral RPV once daily and oral CAB once daily for 4 weeks (optional), followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by an RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks.

Group II: Step 1 SOC Experimental Treatment 1 Intervention

In Step 1, participants received SOC oral ART regimen for up to 24 weeks.

Group III: Step 2 Arm B: SOC Active Control 1 Intervention

In Step 2, participants continued SOC oral ART regimen for 52 weeks.

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

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

Long-acting injectable antiretroviral (ARV) treatments, like cabotegravir/rilpivirine (LA-CAB/RPV), offer a simplified alternative to daily oral medications for HIV, potentially improving adherence and health outcomes for patients.

LA-CAB/RPV is currently the only approved long-acting injectable regimen for HIV treatment in adults and adolescents who are already virologically suppressed, with ongoing studies exploring its use in broader populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting injectable antiretroviral therapy: will it change the future of HIV treatment? Brizzi, M., Pérez, SE., Michienzi, SM., et al.[2023]

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]

In a Phase 2b study involving 97 adults living with HIV-1, the long-acting formulation of cabotegravir and rilpivirine (CAB+RPV) administered every 2 months successfully maintained virologic suppression, with no participants showing HIV-1 RNA levels above 50 copies/ml after 12 months.

The long-acting CAB+RPV treatment had a favorable safety profile, with no new safety concerns identified, and 88% of participants preferred this regimen over their previous daily oral treatment, indicating high treatment satisfaction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting cabotegravir and rilpivirine for HIV-1 suppression: switch to 2-monthly dosing after 5 years of daily oral therapy. Mills, A., Richmond, GJ., Newman, C., et al.[2023]

65.8% of people living with HIV expressed interest in trying a long-acting regimen (LAR) of cabotegravir and rilpivirine, particularly those with unmet needs such as suboptimal adherence and privacy concerns.

Physicians showed a high willingness to offer LAR in cases of strong medical need and for patients with adherence issues, indicating that this treatment could significantly improve patient quality of life and adherence to HIV therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors associated with interest in a long-acting HIV regimen: perspectives of people living with HIV and healthcare providers in four European countries. Akinwunmi, B., Buchenberger, D., Scherzer, J., et al.[2021]

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 pre-exposure prophylaxis (LAI PrEP) with cabotegravir (CAB-LA) and rilpivirine (RPV-LA) was found to be generally well-tolerated, with safety profiles similar to placebo across eight studies involving 666 participants.

Pharmacokinetic analyses indicated that CAB-LA 600 mg administered every 8 weeks was more effective than 800 mg every 12 weeks, and RPV-LA 1200 mg every 8 weeks showed superior results over other dosing regimens, suggesting promising efficacy in preventing HIV-1 infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Pharmacokinetic Profiles of Long-Acting Injectable Antiretroviral Drugs for HIV-1 Pre-Exposure Prophylaxis: A Systematic Review and Meta-analysis of Randomized Trials. Lazarus, G., Wangsaputra, VK., Christianto, ., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10677117/

1599. Real-World Efficacy of Long-Acting Cabotegravir and ... LA-CAB/RPV was highly effective in achieving and maintaining virologic suppression among a large number of patients at an urban HIV clinic.

2. academic.oup.com academic.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.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 ...

4. pubmed.ncbi.nlm.nih.gov pubmed.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 ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2352301824002698

Articles Effectiveness of bi-monthly long-acting injectable ... Large clinical trials have shown the long-term effectiveness of injectable cabotegravir in combination with rilpivirine as maintenance treatment for HIV in well ...

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

Safety and pharmacokinetics of oral and long-acting ... Study findings showed that approved adult dosing of CAB-LA or RPV-LA (every 4 or every 8 weeks) in adolescents achieved comparable exposure to ...

7. 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.

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39853281/

Efficacy, Safety and Retention in Care Among Adolescents ... Long-acting injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) can improve adherence among adolescents and youth with HIV (AYHIV).

9. clinicaltrials.gov clinicaltrials.gov/study/NCT02951052

NCT02951052 | Study Evaluating the Efficacy, Safety, and ... This study is designed to demonstrate the non-inferior antiviral activity of switching to a two drug CAB LA 400 mg + RPV LA 600 mg regimen every 4 weeks.