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Kuwa Free! - Live Free!

ConditionsHIV InfectionsContraceptionDrug-drug Interaction
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexFemale
Age15-24
SponsorUniversity of Alabama at Birmingham

About this trial

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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

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,

Disqualifiers

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,

Trial design

Design model

Parallel

Treatments tested in this trial

  • Cabotegravir/ Rilpivirine

    Drug

    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

  • Etonogestrel (ETG) implant

    Drug

    Contraceptive progestin implants are thin rods inserted under the skin of a woman's arm

  • Intramuscular depo-medroxyprogesterone acetate (IM DMPA)

    Drug

    DMPA (150 mg of depo-medroxyprogesterone acetate (MPA)/ml IMI) is the most commonly used injectable contraceptive worldwide

  • Levonorgestrel

    Drug

    Contraceptive estrogen implants are thin rods inserted under the skin of a woman's arm

  • NNRTI, PI, or INSTI-containing 1st or 2nd line ART regimens

    Drug

    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

Treatment groups

700 Participants
are divided into 7 treatment groups

7

Treatment groups

See each treatment group below.

Group A: Aim 1a (PK study group 1)Experimental treatment 2 interventions
Group B: Aim 1a (PK study group 2)Experimental treatment 2 interventions
Group C: Aim 1a (PK study group 3)Experimental treatment 2 interventions
Group D: Aim 1a (PK study group 4)Active comparator 1 intervention
Group E: Aim 1a (PK study group 5)Active comparator 1 intervention
Group F: Aim 2a (Hybrid trial intervention group)Experimental treatment 1 intervention
Group G: Aim 2a (Hybrid trial comparator group)Active comparator 1 intervention

Trial outcomes

Primary outcomes

1

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.

Time frame
12 or 24 weeks after DMPA or implant initiation, respectively
2

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.

Time frame
48 weeks after study enrollment

Secondary outcomes

1

Adherence to ART (Aim 2a)

For secondary outcome of adherence to ART, the investigators will use multivariate logistic regression to assess associations between study arm and adherence/ medication possession ratio (MPR=\[# pills dispensed - # pills returned\]/\[avg. # doses required per day \* # days of use\]) ≥95% over the preceding month prior to the VL evaluation.

Time frame
3, 6, and 12 months after method initiation
2

Persistence to ART (Aim 2a)

For secondary outcome of persistence to ART, the investigators will use multivariate logistic regression to assess associations between study arm persistence/average MPR since study enrollment.

Time frame
3, 6, and 12 months after method initiation
3

Contraceptive outcome (Aim 2a)

Among participants who are not already using a LA contraceptive method at enrollment and wish to delay pregnancy, the investigators will use Cox proportional hazards models to compare time to LA contraceptive uptake, or incident use, between study arms.

Time frame
3, 6, and 12 months after method initiation

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Alabama at Birmingham

Lead sponsor

Moi Teaching and Referral Hospital

Collaborator

Indiana University

Collaborator

University of Nebraska

Collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Source ClinicalTrials.gov
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