Kuwa Free! - Live Free!
Co-benefits of Co-delivery of Long-acting Antiretrovirals and Contraceptives
2 other identifiers
interventional
700
1 country
1
Brief Summary
The study investigators are conducting foundational pharmacokinetic (PK) and qualitative studies, among 15-24 years old (inclusive) adolescent girls and young women living with HIV (AGYWLHIV) already on oral antiretroviral therapy (ART) and virally suppressed, leading up to a hybrid type I effectiveness-implementation trial randomizing individual AGYWLHIV to receive long-acting (LA) injectable cabotegravir/rilpivirine vs. standard of care within one of Kenya's largest HIV treatment programs. The PK and qualitative studies will investigate potential issues arising from co-delivery and guide delivery of the effectiveness-implementation trial. The PK and qualitative studies will largely be conducted with a sentinel cohort of AGYWLHIV. Learning from this early LA ART use, the investigators will refine the procedures in the LA ART hybrid trial.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable hiv-infections
Started Nov 2021
Longer than P75 for not_applicable hiv-infections
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 26, 2021
CompletedFirst Posted
Study publicly available on registry
September 16, 2021
CompletedStudy Start
First participant enrolled
November 26, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 31, 2027
April 13, 2026
April 1, 2026
5.3 years
August 26, 2021
April 8, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Hormone concentrations with cabotegravir/rilpivirine use (Aim 1a)
To assess differences in hormone concentrations with cabotegravir/rilpivirine use, the investigators will first calculate the progestin geometric mean concentrations at 12 or 24 weeks after DMPA or implant initiation, respectively, for each group. These geometric means will be compared to HIV-negative groups recruited in this study (for the DMPA comparator) or from the PARVI study (for the implants comparator), using geometric mean ratios with 90% confidence intervals (a FDA standard) and the Wilcoxon rank sum test.
12 or 24 weeks after DMPA or implant initiation, respectively
Number of participants with HIV viral suppression (Aim 2a)
Our primary analysis will compare the proportion of participants with viral suppression (via HIV viral load \<40 copies/mL) 48 weeks after study enrollment (primary outcome) in the intervention vs. control arms (primary exposure) using logistic regression, adjusting for age group strata.
48 weeks after study enrollment
Secondary Outcomes (3)
Adherence to ART (Aim 2a)
3, 6, and 12 months after method initiation
Persistence to ART (Aim 2a)
3, 6, and 12 months after method initiation
Contraceptive outcome (Aim 2a)
3, 6, and 12 months after method initiation
Study Arms (7)
Aim 1a (PK study group 1)
EXPERIMENTALInitiating injectable cabotegravir/rilpivirine (LA ART) and DMPA
Aim 1a (PK study group 2)
EXPERIMENTALInitiating injectable cabotegravir/rilpivirine (LA ART) and and etonogestrel implant
Aim 1a (PK study group 3)
EXPERIMENTALInitiating injectable cabotegravir/rilpivirine (LA ART) and levonorgestrel implant.
Aim 1a (PK study group 4)
ACTIVE COMPARATORReceiving injectable cabotegravir/ rilpivirine (LA ART) and not using any hormonal contraceptive method (e.g. copper IUD)
Aim 1a (PK study group 5)
ACTIVE COMPARATORAGYW without HIV and not exposed to antiretrovirals (e.g., for PrEP) initiating DMPA
Aim 2a (Hybrid trial intervention group)
EXPERIMENTALAGYW with viral suppression on their current ART regimen to switch to cabotegravir/ rilpivirine.
Aim 2a (Hybrid trial comparator group)
ACTIVE COMPARATORAGYW with viral suppression to continue their oral ART regimen.
Interventions
ART that concurrently contains combinations of non-nucleoside reverse transcriptase inhibitors (NNRTIs), such as efavirenz, and protease-inhibitors (PIs), such as atazanavir/ritonavir or lopinavir/ritonavir, or integrase inhibitors (INSTIs), such as raltegravir or dolutegravir
Contraceptive progestin implants are thin rods inserted under the skin of a woman's arm
DMPA (150 mg of depo-medroxyprogesterone acetate (MPA)/ml IMI) is the most commonly used injectable contraceptive worldwide
Contraceptive estrogen implants are thin rods inserted under the skin of a woman's arm
For initial injection participants will be given CABENUVA 600-mg/900-mg Kit: (single-dose vial of 600 mg/3 mL (200 mg/mL) cabotegravir , single-dose vial of 900 mg/3 mL (300 mg/mL) rilpivirin). For subsequent injections participants will be given CABENUVA 400-mg/600-mg Kit: (single-dose vial of 400 mg/2 mL (200 mg/mL) cabotegravir, single-dose vial of 600 mg/2 mL (300 mg/mL) rilpivirine) CABENUVA® is owned by or licensed to the ViiV Healthcare group of companies, GlaxoSmithKline Research Triangle Park, NC 27709
Eligibility Criteria
You may qualify if:
- Female sex,
- HIV-positive (for PK groups #1-4) or HIV-uninfected (for PK group #5 only),
- Age 15-24 years at the time of enrollment,
- Documented or confirmed viral suppression for HIV (defined as \<40 copies/mL) within 6 months prior to study enrollment,
- Have been on the study oral drug for at least 4 weeks for the PK groups #1-4,
- Have initiated and intends to use DMPA or implant for at least another three or 6 months, respectively,
- Willing to undergo phlebotomy every 4-12 weeks for the duration of the study period
- Able to consent or assent (with parental consent) for study participation in English or Kiswahili
You may not qualify if:
- Already be on ART that concurrently contains combinations of non-nucleoside reverse transcriptase inhibitors (NNRTIs), such as efavirenz, and protease-inhibitors (PIs), such as atazanavir/ritonavir or lopinavir/ritonavir, or integrase inhibitors (INSTIs), such as raltegravir or dolutegravir
- Currently pregnant or intends to become pregnant or breastfeeding within the next 12 or 24 weeks for DMPA or implant groups, respectively,
- Have had unprotected sex in the last two weeks or be currently pregnant via urine pregnancy testing,
- Use or anticipated use of drugs for the duration of the study period known to interact with hormonal implants or the study ART regimen,
- Current or planned concomitant use of other hormonal contraceptives,
- Be obese (BMI≥30),
- Evidence of Hepatitis B virus (HBV) infection based on the results of testing for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc), Hepatitis B surface antibody (anti-HBs) and HBV Deoxyribonucleic acid (DNA) as follows: positive for HBsAg being excluded or negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA are excluded (of note, participants positive for anti-HBc (negative HBsAg status) and positive for anti-HBs (past and/or current evidence) are immune to HBV and are not excluded).
- Serum ALT\>5x ULN at the time of screening,
- Serum creatinine \>2.5x ULN at the time of screening.
- Participating in PK study for study participants,
- Self-identifying as provider, program person, policy-maker, or stakeholder relevant to the study topics, and age 18 years of age or older,
- Able to consent for study participation in English or Kiswahili
- Female sex,
- HIV-positive,
- Age 15-24 years at the time of enrollment,
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Alabama at Birminghamlead
- University of Nebraskacollaborator
- Moi Teaching and Referral Hospitalcollaborator
- Indiana Universitycollaborator
- National Institute of Allergy and Infectious Diseases (NIAID)collaborator
Study Sites (1)
Academic Model Providing Access to Healthcare (AMPATH) Moi Teaching And Referral Hospital (MTRH)
Eldoret, Kenya, Kenya
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Rena Patel, MD, MPH, MPhil
University of Alabama at Birmingham
- PRINCIPAL INVESTIGATOR
Edwin Were
Moi Teaching and Referral Hospital
- PRINCIPAL INVESTIGATOR
Edith Apondi
MTRH Adolescent Rafiki Clinic and Pediatric Program at AMPATH
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- Participants and care providers will not be masked (open label), but the principle and site-principal investigators and study statistician will be blinded to arm allocation.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
August 26, 2021
First Posted
September 16, 2021
Study Start
November 26, 2021
Primary Completion (Estimated)
March 31, 2027
Study Completion (Estimated)
March 31, 2027
Last Updated
April 13, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL
- Time Frame
- Starting 9 months and ending 36 months after article publication
- Access Criteria
- Investigators whose proposed use of the data has been approved by the investigators
De-identified IPD that underlies the results reported in a publication will be provided. Data sharing will begin 9 months after article publication and will be available for up to 36 months. Data will be made available to qualified researchers whose proposed research has received IRB approval. The data will be provided through a data repository following the execution of a data-sharing agreement.