HPTN 084

A Phase 3 Double Blind Safety and Efficacy Study of Long-Acting Injectable Cabotegravir Compared to Daily Oral TDF/FTC for Pre-Exposure Prophylaxis in HIV-Uninfected Women.

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Study Documents
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Study Website
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LATEST PRESS RELEASE
9 November 2020

HPTN 084 Study Demonstrates Superiority of Injectable Cabotegravir to Oral TDF/FTC for the Prevention of HIV in Cisgender Women in Sub-Saharan Africa

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HPTN 084 logo

What is HPTN 084?

HPTN 084 (The LIFE Study) is a study being done to evaluate the safety and efficacy of the injectable agent, cabotegravir (CAB LA) compared to daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), for pre-exposure prophylaxis (PrEP) in HIV-uninfected women.

Who participated in the study?

HPTN 084 enrolled 3,224 women 18 to 45 years old in sub-Saharan Africa who were at risk for acquiring HIV.

Why is HPTN 084 important?

PrEP agents are needed that do not depend on daily or near-daily pill-taking. The development of alternative agents for PrEP, and/or more adherence-friendly schedules for currently available agents, could increase prevention choices and increase acceptability. Long-acting injectable agents have the potential to prevent HIV acquisition without relying on adherence to a daily oral regimen.

 

The women of 084

 

What happened during the study?

Once randomized to one of two arms, participants moved through the steps below and will be followed for up to 4 and a half years (active drugs are shown in bold text):

Step 1:

Arm A – Daily oral CAB (30 mg tablets) and oral TDF/FTC placebo for five weeks plus an HIV prevention package including behavioral risk reduction and adherence counseling, provision of condoms.

Arm B – Daily oral TDF/FTC (300 mg/200 mg fixed-dose combination tablets) and oral CAB placebo for five weeks plus an HIV prevention package including behavioral risk reduction and adherence counseling, provision of condoms.

A participant that becomes HIV-infected during Step 1 of the study will permanently discontinue study product and will be terminated from the study, and referred for HIV-related care.

Step 2:

Arm A – CAB LA (600 mg as a single intramuscular [IM] injection at two time points 4 weeks apart and every 8 weeks thereafter) and daily oral TDF/FTC placebo plus an HIV prevention package including behavioral risk reduction and adherence counseling, provision of condoms.

Arm B – Daily oral TDF/FTC (300/200 mg fixed-dose combination tablets) and IM placebo at two time points 4 weeks apart and every 8 weeks thereafter (matching vehicle, identical volume as active injectable product in Arm A) plus an HIV prevention package including behavioral risk reduction and adherence counseling, provision of condoms.

This step will continue until the required number of endpoints (111) is reached, estimated to be 81 weeks after enrolling the last participant.

A participant that becomes HIV-infected during Step 2 of the study will permanently discontinue study product, be placed on immediate suppressive ART, and be followed for 52 weeks after their last injection, after which their participation in the study will end and they will be transitioned to continued HIV-related care.

Step 3:

Arms A and B – Open-label daily TDF/FTC (in order to cover the pharmacokinetic [PK] tail for Arm A participants) will be provided no later than eight weeks after the last injection visit, for up to 48 weeks plus an HIV prevention package including behavioral risk reduction and adherence counseling, and provision of condoms.  Participants will then transition to locally available HIV prevention services, including services for PrEP, if available.

A participant with confirmed HIV infection during Step 3 will be followed at least for the duration of Step 3.

 

084 design
 

What were the results of the study?

In November 2020, researchers from the HPTN announced the HPTN 084 clinical trial data indicating that a pre-exposure prophylaxis (PrEP) regimen of long-acting cabotegravir (CAB LA) injections once every eight weeks was safe and superior to daily oral tenofovir/emtricitabine (TDF/FTC) for HIV prevention among cisgender women in sub-Saharan Africa. During a planned review of study data, an independent Data and Safety Monitoring Board (DSMB) recommended the study sponsor―the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health―stop the blinded phase of the trial and share the results. The study was originally designed to continue through 2022. Read more.

 


 

Study Documents

 

HPTN 084 Open Label Extension (OLE)

 

HPTN 084 Dear Participant Letter

 

HPTN 084 Version 4.0

 

HPTN 084 Version 3.0

 

HPTN 084 Version 2.0

 

HPTN 084 Version 1.0

 

HPTN 084 V3.0 OLE Training

 

COVID-19 Resources

 

Presentations
  • Long acting cabotegravir: updated efficacy and safety results from HPTN 084 (AIDS 2022) (Slides)
  • The relative cost-effectiveness of long-acting injectable cabotegravir versus oral pre-exposure prophylaxis: A modelled economic evaluation and threshold analysis in South Africa based on the HPTN 083 and 084 (AIDS 2022) (Slides)
  • Acceptability of injectable versus daily oral pills for HIV prevention: Lesson from HPTN 084 (AIDS 2022) (Poster)
  • Evaluation of CAB-LA Safety and PK in Pregnant Women in the Blinded Phase of HPTN 084 (CROI 2022​​​​​​) (Poster)
  • Counterfactual Estimation of CAB-LA Efficacy Against Placebo Using External Trial Data (CROI 2022) (Slides)
  • Estimated Long-acting PrEP Effectiveness in the HPTN 084 Cohort using a Model-Based Counterfactual (IAS 2021) (Slides)
  • Long-Acting Injectable PrEP in Women: Laboratory Analysis of HIV Infections in HPTN 084 (IAS 2021) (Poster)
  • Long-Acting Injectable Cabotegravir is Safe and Effective in Preventing HIV Infection in Cisgender Women: Results from HPTN 084 (HIV R4P 2021) (Video) (Abstract)
  • Long-acting cabotegravir (CAB LA): Planning for Success Across Global at-risk Populations (AIDS 2020) (Slide) (Program)
  • Community Presentations for HPTN 083 Results, including HPTN 084 implications (May 2020) (Results Webinar) (Webinar Video)
  • Cabotegravir for PrEP - Injection Training (Video)

 

Press

 

Resources:

 

You can request access to private documents (i.e. SSPs) in Microsoft Team by emailing Jeff Webb jwebb@fhi360.org. 
You will need a Microsoft account to log in to Teams. Click here for instructions on setting up your Microsoft account and accessing the Teams platform.

 

➤ HPTN 084 SSP

(Click to Expand)
Previous versions of the SSP sections are available upon request.

Full HPTN 084 SSP (Combined Sections)

HPTN 084 Study-Specific Procedures Manual Overview and Version Control

Cover Page

Section 1: Introduction

Section 2: Protocol

Section 3: Document Requirements

Section 4: Continuation in Protocol Version 3.0 (OLE)

Section 5: Study Procedures

Section 6: Visit Checklists

Section 7: Participant Retention

Section 8: Study Product Considerations

Section 9: Clinical Considerations

Section 10: Adverse Event Reporting and Safety Monitoring

Section 11: Laboratory and Specimen Management Procedures

Section 12: Counseling Considerations

Section 13: Data Management

Section 14: Computer Assisted Self-Interview (CASI)

Section 15: Reporting Plan

Section 16: Data Communiqués

Section 17: COVID-10 Measures

Appendix I: Guidance for the Management of “Discordant/discrepant” HIV Testing Results – HPTN 083 and 084

 

Study Details

Protocol Status: Closed to Accrual
Study Purpose:

To evaluate the safety and efficacy of the injectable agent, cabotegravir (CAB LA) compared to daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), for pre-exposure prophylaxis (PrEP) in HIV-uninfected women.

Study Design:

Multi-site, double blind, two-arm, randomized (1:1), controlled superiority trial of the safety and efficacy of CAB LA compared to daily oral TDF/FTC for HIV prevention.

Study Population:

HIV-uninfected women at risk for acquiring HIV, 18 to 45 years old.

Study Size:

Approximately 3,200 women will be enrolled.

Study Duration:

Approximately 4.6 years total, with individual participants being followed on randomized study product between 1.6 years (for the last enrolling participants) to approximately 3.6 years (for the earliest enrolling participants), and on oral TDF/ FTC for an additional 48 weeks. Accrual will require approximately 2 years.

Treatment Regimen:

Once randomized to one of two arms, participants will move through the following steps:

Step 1, Oral Run-in Phase:
Arm A – Daily oral cabotegravir (CAB) and oral TDF/FTC placebo for five weeks plus an HIV prevention package including behavioral risk reduction and adherence counseling, provision of condoms.

Arm B – Daily TDF/FTC and oral CAB placebo for five weeks plus an HIV prevention package
including behavioral risk reduction and adherence counseling, provision of condoms.

Step 2, Injection Phase:
Arm A – CAB LA as a single intramuscular [IM] injection at two time points four
weeks apart and every eight weeks thereafter and daily oral TDF/FTC placebo plus an HIV
prevention package including behavioral risk reduction and adherence counseling, provision of
condoms.

Arm B – Daily TDF/FTC and IM placebo (matching vehicle, identical volume as active injectable product in Arm A) at two time points four weeks apart and every eight weeks thereafter plus an HIV prevention package including behavioral risk reduction and adherence counseling, provision of condoms.

Step 2 will continue until the required number of endpoints (111) is reached, estimated to be 81 weeks after enrolling the last participant.

Step 3, Follow-up Phase:
Arms A and B – Open-label daily TDF/FTC (in order to cover the pharmacokinetic [PK] tail for Arm A participants) will be provided no later than eight weeks after the last injection visit, for up to 48 weeks plus an HIV prevention package including behavioral risk reduction and adherence counseling, and provision of condoms. Participants will then transition to locally available HIV prevention services, including services for PrEP, if available.

Primary Objectives:

• Efficacy: To evaluate the relative efficacy of oral CAB/CAB LA (oral run-in and injections, Steps 1 and 2) vs. daily oral TDF/FTC for HIV prevention (Steps 1 and 2).

• Safety: To evaluate the relative safety of oral CAB/CAB LA (oral run-in and injections, Steps 1 and 2) vs. daily oral TDF/FTC for HIV prevention (Steps 1 and 2).

Secondary Objectives:

• To compare HIV incidence among participants receiving oral CAB/CAB LA vs. daily oral TDF/FTC (Steps 1, 2 and 3).
• To evaluate relative efficacy of oral CAB/CAB LA vs. oral TDF/FTC in subgroups defined by the baseline factors of: age, herpes simplex virus-2 (HSV-2) serostatus, contraceptive method, and body mass index (BMI).

• To describe and model the relationship between HIV incidence and drug concentration, within each arm.

• To describe the distribution and correlates of drug concentration, within each arm.

• To compare the acceptability of and preferences for CAB LA vs. oral TDF/FTC.

Other Objectives:

Tertiary
• To estimate and compare sexual risk behaviors, as measured by self-report and rates of incident sexually transmitted infections (STIs), between study arms.

• To compare Grade >2 adverse event (AE) rates in women with baseline BMI </≥ 25 kg/m2, within each study arm.

• To compare pregnancy incidence and outcomes between arms.

• To evaluate rates of HIV drug resistance among participants who acquire HIV infection during the study among participants receiving oral CAB/CAB LA vs. oral TDF/FTC.

• To determine plasma concentrations of medroxyprogesterone (DMPA) or norethisterone (NET-EN) when co-administered with CAB LA.

• To determine lutenizing hormone (LH), follicular stimulating hormone (FSH), and progesterone in subjects receiving either DMPA or NET-EN when co-administered with CAB LA.

Exploratory
• To compare the estimated programmatic cost, cost-effectiveness and disease impact indicators of CAB LA vs. daily oral TDF/FTC vs. no PrEP for HIV-uninfected women in the study sites locations.

• To perform secondary laboratory assessments that may include evaluation of factors related to HIV infection, hepatitis infection, and other infections; antiretroviral (ARV) drug use; pharmacogenomics; characterization of HIV in infected participants; and evaluation of laboratory assays related to the study objectives.