Long-Acting Antiretroviral Therapy for HIV

Recruiting at 30 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

456 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the long-acting antiretroviral therapy for HIV?

Research shows that the long-acting injectable combination of cabotegravir and rilpivirine is as effective as daily oral antiretroviral therapy for maintaining HIV suppression, offering a convenient option for those who struggle with daily medication adherence. ^{1 2 3 4 5}

Is long-acting antiretroviral therapy for HIV safe for humans?

Long-acting antiretroviral therapy using cabotegravir (CAB-LA) and rilpivirine (RPV-LA) has been generally well-tolerated in clinical trials, with safety profiles similar to placebo, meaning they did not cause more side effects than a non-active treatment. These treatments have been approved for use in people with HIV who have their virus under control, and further studies are ongoing to confirm their safety in broader populations. ^{2 3 6 7 8}

How is the long-acting antiretroviral therapy for HIV different from other treatments?

This treatment is unique because it involves long-acting injectable forms of cabotegravir and rilpivirine, which are administered every 4 or 8 weeks, reducing the need for daily pills. This can improve adherence and quality of life for patients who struggle with daily medication routines. ^{2 3 4 5 9}

What is the purpose of this trial?

The purpose of this study was to compare the efficacy, safety, and durability of two different strategies to treat participants with a history of sub-optimal adherence and control of their HIV infection: long-acting (LA) antiretroviral therapy (ART) and all-oral standard of care (SOC).

Research Team

Aadia Rana, M.D.

Principal Investigator

Alabama CTU

Eligibility Criteria

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.

I have advanced liver disease or a history of liver cirrhosis.

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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]

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]

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]

References

1. England 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. [2021]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

Long-acting injectable antiretroviral therapy: will it change the future of HIV treatment? [2023]

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

Identifying appropriate candidates for long-acting antiretroviral therapy: findings from a survey of health care providers in the ATLAS-2M trial. [2021]

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

Patient-Reported Outcomes Through 1 Year of an HIV-1 Clinical Trial Evaluating Long-Acting Cabotegravir and Rilpivirine Administered Every 4 or 8 Weeks (ATLAS-2M). [2022]

6. Switzerland 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. [2021]

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

Therapeutic review of cabotegravir/rilpivirine long-acting antiretroviral injectable and implementation considerations at an HIV specialty clinic. [2022]

8. England 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. [2023]

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

Efficacy, Safety, and Durability of Long-Acting Cabotegravir and Rilpivirine in Adults With Human Immunodeficiency Virus Type 1 Infection: 5-Year Results From the LATTE-2 Study. [2022]