The LATITUDE Study: Long-Acting Therapy to Improve Treatment SUccess in Daily LifE

NCT03635788 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 2 other identifiers: ACTG A535930104
• Study Type: interventional
• Target: 456
• Locations: 2 countries
• Sites: 33

Brief Summary

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).

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (1)

• Cumulative Probability of Regimen Failure in Step 2 at Any Time Post Randomization and Week 48 Visit

  Regimen failure was defined as the occurrence of the earlier of the following two events * virologic failure (defined as two consecutive HIV-1 RNA \>200 copies/mL after Step 2 randomization * Permanent discontinuation of randomized study treatment prior to or at Week 48 visit Cumulative probability was calculated by Kaplan-Meier method.

  From Step 2 randomization to Step 2, Week 48 visit (up to 50 weeks)

Secondary Outcomes (19)

• Cumulative Probability of Virologic Failure in Step 2 at Any Time Post Randomization to Week 48 Visit

  From Step 2 randomization to Step 2, Week 48 visit (up to 50 weeks)

• Cumulative Probability of the Treatment-related Failure in Step 2 at Any Time Post Randomization to Week 48 Visit

  From after Step 2 randomization to Step 2, Week 48 (up to 50 weeks)

• Number of Participants With Virologic Non-success (>= 50 Copies/ml)

  from Step 2 randomization to Step 2, Week 48 (up to 50 weeks)

• Number of Participants With Virologic Non-success (>= 200 Copies/ml)

  From Step 2 randomization to Step 2, Week 48 (up to 50 weeks)

• Percentage of Participants With Plasma HIV-1 RNA Level Less Than 50 Copies/mL at Scheduled Study Visits on Steps 1

  Measured from Step 1 entry through Step 1, Week 20 visit

Study Arms (3)

Step 1 SOC

OTHER

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

Drug: Standard of Care (SOC) Oral ART

Step 2 Arm A: LA ART

EXPERIMENTAL

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.

Drug: Oral RPV; Drug: Oral CAB; Drug: RPV-LA Loading Dose; Drug: CAB-LA Loading Dose; Drug: RPV-LA Maintenance Dose; Drug: CAB-LA Maintenance Dose

Step 2 Arm B: SOC

ACTIVE COMPARATOR

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

Drug: Standard of Care (SOC) Oral ART

Interventions

Standard of Care (SOC) Oral ART DRUG

SOC oral ART regimen must include at least 3 drugs with 2 or more drugs predicted to be fully active, including a boosted protease inhibitor (PI) and/or an integrase strand transfer inhibitor (INSTI)

Step 1 SOC; Step 2 Arm B: SOC

Oral RPV DRUG

RPV 25 mg tablets

Also known as: Rilpivirine

Step 2 Arm A: LA ART

Oral CAB DRUG

CAB 30 mg tablets

Also known as: Cabotegravir, GSK1265744

Step 2 Arm A: LA ART

RPV-LA Loading Dose DRUG

900 mg administered as one 3 mL (900 mg) intramuscular injection in the gluteal muscle

Also known as: Rilpivirine Long-Acting Injectable

Step 2 Arm A: LA ART

CAB-LA Loading Dose DRUG

600 mg administered as one 3 mL (600 mg) intramuscular injection in the gluteal muscle

Also known as: Cabotegravir Long-Acting Injectable

Step 2 Arm A: LA ART

RPV-LA Maintenance Dose DRUG

600 mg administered as one 2 mL (600 mg) intramuscular injection in the gluteal muscle

Also known as: Rilpivirine Long-Acting Injectable

Step 2 Arm A: LA ART

CAB-LA Maintenance Dose DRUG

400 mg administered as one 2 mL (400 mg) intramuscular injection in the gluteal muscle

Also known as: Cabotegravir Long-Acting Injectable

Step 2 Arm A: LA ART

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load.
• NOTE: The term "licensed" referred to an FDA-approved kit, which was required for all IND studies.
• WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandated that confirmation of the initial test result had to use a test that was different from the one used for the initial assessment. A reactive initial rapid test had to be confirmed by either another type of rapid assay or an E/CIA that was based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load.
• HIV-1 Plasma viral load (VL) greater than 200 copies/mL within 12 months prior to study entry by any US laboratory that had a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent, unless the participant had been lost to clinical follow-up (see protocol for more information) and no viral load result was available within the last 12 months.

You may not qualify if:

• Evidence of non-adherence to ART according to at least one of the following criteria:
• Poor virologic response within 18 months prior to study entry (defined as less than 1 log10 decrease in HIV-1 RNA or HIV-1 RNA greater than 200 copies/mL at two time points at least 4 weeks apart) in individuals who had been prescribed ART for at least 6 consecutive months.
• Lost to clinical follow-up within 18 months prior to study entry with ART non-adherence for greater than or equal to 6 consecutive months.
• NOTE: Lost to clinical follow-up was defined as either no contact with the provider or missing greater than or equal to 1 appointment in a 6-month period. ART non-adherence was defined as a lapse in ART greater than or equal to 7 days (consecutive or non-consecutive), in the 6-month period where they were lost to clinical follow-up per participant report.
• No evidence of any clinically relevant RPV or INSTI resistance-associated mutations (see protocol for more information) through commercially available genotypic (or phenotypic, if available) analyses from any laboratory that had a CLIA certification or equivalent within 60 days of study entry (see protocol for more information), nor history of such mutations on review of prior HIV-1 drug resistance tests by the site investigator. For participants in whom a screening HIV-1 conventional genotype could not be resulted by the testing laboratory, review of historical genotypes and treatment history by the IoR could be used to satisfy this criterion as indicated in the protocol.
• Ability of site clinician, in conjunction with the participant, to construct an oral induction antiretroviral (ARV) regimen that had to include at least three ARVs of which at least two had to be predicted to be fully active. The regimen had to include PI/cobi and/or an INSTI based on screening and/or historic resistance testing.
• Laboratory values obtained within 60 days prior to study entry by any laboratory that had a CLIA certification or its equivalent:
• Hemoglobin greater than or equal to 9.0 g/dL
• Absolute neutrophil count (ANC) greater than or equal to 600/mm\^3
• Alanine aminotransferase (ALT) less than or equal to 3 x upper limit of normal (ULN)
• Creatinine Clearance (CrCl) greater than or equal to 50 mL/min estimated by Chronic Kidney Disease Epidemiology Collaboration equation (CKD-Epi).
• For participants of reproductive potential, a negative serum or urine pregnancy test with a sensitivity of less than or equal to 25 mIU/mL at screening. This was repeated again at study entry.
• NOTE: Participants were considered to be NOT of reproductive potential if: 1) they had had amenorrhea for at least 12 consecutive months prior to study entry (i.e., who had had no menses within 12 months prior to study entry), and had a documented follicle-stimulating hormone (FSH) greater than 40 IU/mL; OR 2) an FSH level was not available, but they had had 24 consecutive months of amenorrhea (in the absence of medications known to induce amenorrhea); OR 3) they reported having undergone surgical sterilization (e.g., hysterectomy, or bilateral oophorectomy, or bilateral tubal ligation/hysteroscopic tubal occlusion).
• Contraception Requirements
• Participants of Reproductive Potential: Participants of reproductive potential, who were participating in sexual activity that could lead to pregnancy, had to agree to use at least one of the listed highly effective methods for contraception from 30 days prior to the first dose of study medication, while receiving the study drugs, and for 30 days after stopping oral medications, or the duration specified in the product label if receiving study drugs not supplied by the study, or 52 weeks after stopping RPV-LA or CAB-LA. Acceptable methods of contraception included:

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• ViiV Healthcare: collaborator

Study Sites (33)

Alabama CRS

Birmingham, Alabama, 35294, United States

Location

University of Southern California CRS

Los Angeles, California, 90033-1079, United States

Location

UCLA CARE Center CRS

Los Angeles, California, 90035, United States

Location

UCSD Antiviral Research Center CRS

San Diego, California, 92103, United States

Location

Ucsf Hiv/Aids Crs

San Francisco, California, 94110, United States

Location

Harbor-UCLA CRS

Torrance, California, 90502, United States

Location

University of Colorado Hospital CRS

Aurora, Colorado, 80045, United States

Location

Univ. of Florida Jacksonville NICHD CRS

Jacksonville, Florida, 32209, United States

Location

The Ponce de Leon Center CRS

Atlanta, Georgia, 30308-2012, United States

Location

Northwestern University CRS

Chicago, Illinois, 60611, United States

Location

Rush University CRS

Chicago, Illinois, 60612, United States

Location

Johns Hopkins University CRS

Baltimore, Maryland, 21205, United States

Location

Massachusetts General Hospital CRS (MGH CRS)

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital Therapeutics Clinical Research Site (BWH TCRS) CRS

Boston, Massachusetts, 02115, United States

Location

Washington University Therapeutics (WT) CRS

St Louis, Missouri, 63110-1010, United States

Location

New Jersey Medical School Clinical Research Center CRS

Newark, New Jersey, 07103, United States

Location

Weill Cornell Chelsea CRS

New York, New York, 10010, United States

Location

Columbia P&S CRS

New York, New York, 10032-3732, United States

Location

Weill Cornell Uptown CRS

New York, New York, 10065, United States

Location

SUNY Stony Brook NICHD CRS

Stony Brook, New York, 11794, United States

Location

Jacobi Med. Ctr. Bronx NICHD CRS

The Bronx, New York, 10461, United States

Location

Chapel Hill CRS

Chapel Hill, North Carolina, 27599, United States

Location

Greensboro CRS

Greensboro, North Carolina, 27401, United States

Location

Cincinnati Clinical Research Site

Cincinnati, Ohio, 45219, United States

Location

Case Clinical Research Site

Cleveland, Ohio, 44106, United States

Location

Ohio State University CRS

Columbus, Ohio, 43210, United States

Location

Penn Therapeutics, CRS

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh CRS

Pittsburgh, Pennsylvania, 15213, United States

Location

The Miriam Hospital Clinical Research Site (TMH CRS) CRS

Providence, Rhode Island, 02906, United States

Location

Vanderbilt Therapeutics (VT) CRS

Nashville, Tennessee, 37204, United States

Location

Houston AIDS Research Team CRS

Houston, Texas, 77030, United States

Location

University of Washington AIDS CRS

Seattle, Washington, 98104-9929, United States

Location

Puerto Rico AIDS Clinical Trials Unit CRS

San Juan, 00935, Puerto Rico

Location

Related Publications (2)

• Okesanya OJ, Ayeni RA, Amadin P, Ngwoke I, Amisu BO, Ukoaka BM, Ahmed MM, Oso TA, Musa SS, Lucero-Prisno DE. Advances in HIV Treatment and Vaccine Development: Emerging Therapies and Breakthrough Strategies for Long-Term Control. AIDS Res Treat. 2025 Jul 4;2025:6829446. doi: 10.1155/arat/6829446. eCollection 2025.

  PMID: 40655875 DERIVED

• Pluznik JA, Nijhawan AE, Spaulding AC. Does Anything Work? Improving HIV Care Engagement for Individuals Transitioning out of Correctional Settings. J Acquir Immune Defic Syndr. 2021 Mar 1;86(3):286-287. doi: 10.1097/QAI.0000000000002599. No abstract available.

  PMID: 33560746 DERIVED

Related Links

• The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 (Clarification, August 2009).
• Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010
• FDA Snapshot algorithm
• IAS October/November 2022 Update of the Drug Resistance Mutations in HIV-1
• Alcohol Use Disorders Identification Test

MeSH Terms

Conditions

HIV Infections

Interventions

Standard of Care; Rilpivirine; cabotegravir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Nitriles; Organic Chemicals; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

The trial was stopped per DSMB recommendation when the primary outcome measure did not meet the stopping criteria used at the interim efficacy review. Primary analysis included overrun data up to the DSMB review date and final confidence interval was adjusted for type I error spent at prior interim efficacy.

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, a DLH Holdings Company

ACTGCT.gov@fstrf.org

(301) 628-3348

Study Officials

• Aadia Rana, M.D.

  Alabama CTU

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2018
• First Posted: August 17, 2018
• Study Start: March 28, 2019
• Primary Completion: February 12, 2024
• Study Completion (Estimated): August 30, 2026
• Last Updated: September 2, 2025
• Results First Posted: April 24, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH.
• Access Criteria: * With whom? * Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group. * For what types of analyses? * To achieve aims in the proposal approved by the AIDS Clinical Trials Group. * By what mechanism will data be made available? * Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at: https://submit.mis.s-3.net/. Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data.

Locations

US (32); PR (1)