HIV
Conditions
Keywords
Cabotegravir Injectable Suspension, PrEP, HIV Treatment and Prevention, Community Health
Brief summary
The overall purpose of this SEARCH CAB-LA (Cabotegravir Injectable Suspension) randomized extension study is to determine if adding the option of CAB-LA as a prevention choice using a person-centered dynamic choice HIV (human immunodeficiency virus) prevention model, with option to switch products over time, compared to the standard of care: 1) increases prevention coverage; 2) reduces HIV incident infection; and 3) increases prevention coverage during periods of self-assessed risk of HIV infection, in three settings in rural Uganda and Kenya. In addition, this study will describe implementation of a person-centered model for dynamic choice HIV prevention including CAB-LA, using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) evaluation framework among persons randomized to the intervention arm.
Detailed description
The SEARCH CAB-LA (Cabotegravir Injectable Suspension) dynamic choice HIV prevention study is a randomized extension study of a person-centered Dynamic Choice HIV Prevention model for delivering existing evidence-based biomedical prevention interventions vs. standard of care (SOC). The study is conducted in 3 settings in rural Western Uganda and Kenya: antenatal (ANC) clinics, the outpatient department (primary care clinics), and in community settings. Participants previously randomized to Dynamic Choice HIV Prevention or SOC are re-consented and remain in their initial randomized arm. During the extension, the Dynamic Choice HIV Prevention intervention offers participants choices of biomedical prevention product (oral Pre-Exposure Prophylaxis (PrEP), oral post-exposure prophylaxis (PEP), or Cabotegravir Injectable Suspension (CAB-LA) on an ongoing basis with the option to switch products over time based on participant preference and perceived risk. The primary endpoint is proportion of time that is covered by a biomedical prevention product over 48 weeks; secondary endpoints are: i) incident HIV infection over 48 weeks; and, ii) proportion of time during which a participant reports risk of HIV infection that is covered by a biomedical prevention product over 48 weeks. Participants in the intervention arm only are reconsented at 48 weeks for implementation evaluation up to 96 weeks.
Interventions
CAB-LA will be one of the options for the Dynamic Choice Delivery intervention arm. CAB-LA will be a choice for at-risk adults and adolescents weighing at least 35 kg for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection. Single-dose vial containing 600 mg/3 mL (200 mg/mL) of cabotegravir is a white to light pink, free-flowing, extended-release injectable suspension. CAB-LA administration will occur at health facilities.
OTHERDynamic Choice Delivery Model
The Dynamic Choice Delivery Model includes integrated PrEP (including CAB-LA) and PEP services at outpatient clinics, antenatal clinics, and via VHT workers in community households. The procedures for each trial include PrEP/PEP counseling and services, choice of service location, HIV testing options, option for longer PrEP refills, provision of a clinical officer's or nurse's mobile telephone number for immediate PEP starts any day of the week, assessment of PrEP/PEP barriers and personalized actions, psychologic supports for traumatic experiences, and offer of concurrent, additional health or prevention related services.
OTHERStandard of Care
The standard of care differs according to country but does not routinely offer PEP or PrEP to clients seeking services, does not offer choice of service location, HIV testing option or access to medical provider mobile phone number.
Sponsors
University of California, San Francisco
Infectious Diseases Research Collaboration, Uganda
Makerere University
Kenya Medical Research Institute
University of California, Berkeley
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Institute of Mental Health (NIMH)
National Heart, Lung, and Blood Institute (NHLBI)
ViiV Healthcare
University of Pittsburgh
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Participants initially randomized to the Dynamic Choice Prevention delivery model will be given the option to use CAB-LA as part of the dynamic choice prevention delivery package. Participants initially randomized to standard of care will continue to receive standard of care.
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Inclusion criteria for the Extension include: 1. Enrollment in a SEARCH Sapphire Dynamic prevention study (NCT04810650) 2. HIV negative at start of extension 3. Residing in study region Additional inclusion criteria to access CAB-LA as a prevention option 1. Not pregnant or breastfeeding at time of initial CAB-LA injection 2. Participant weighs at least 35kg
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Biomedical Prevention Covered Time | 48 weeks | Number of days participant taking biomedical prevention divided by number of days participant biomedical prevention use measured. Biomedical prevention includes PrEP tenofovir disoproxil fumarate/lamivudine (TDF/3TC) or cabotegravir long-acting injectable (CAB-LA) and PEP |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HIV Incident Infection | 48 weeks | HIV incidence rate: number of HIV incident infections divided by number at risk (HIV incidence per 100 person-years) |
| Biomedical Prevention During Periods of Self Assessed HIV Risk | 48 weeks (during follow-up weeks 48-96) | Number of days participant was taking biomedical prevention divided by number of days participant had biomedical prevention use measured and self-assessed with HIV risk (intervention participants only). Participants in the intervention arm only were reconsented at 48 weeks for evaluation through 96 weeks. Participants in the standard of care discontinued the study at 48 weeks and were not analyzed for this outcome. |
Countries
Kenya, Uganda
Contacts
PRINCIPAL_INVESTIGATORDiane Havlir, MD
University of California, San Francisco
PRINCIPAL_INVESTIGATORMoses Kamya, MBChB, PhD
Makerere University
PRINCIPAL_INVESTIGATORMaya Petersen, MD, PhD
University of California, Berkeley
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dynamic Choice Prevention (Including CAB LA) The Dynamic Choice Delivery Model includes integrated PrEP and PEP services at outpatient clinics, antenatal clinics, and via VHT workers in community households. CAB-LA will be integrated into the dynamic choice delivery model as an additional biomedical prevention option in a patient-centered delivery model based on the precede framework.
Cabotegravir Injectable Suspension: CAB-LA will be one of the options for the Dynamic Choice Delivery intervention arm. CAB-LA will be a choice for at-risk adults and adolescents weighing at least 35 kg for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection. Single-dose vial containing 600 mg/3 mL (200 mg/mL) of cabotegravir is a white to light pink, free-flowing, extended-release injectable suspension. CAB-LA administration will occur at health facilities.
Dynamic Choice Delivery Model: includes integrated PrEP (including CAB-LA) and PEP services at outpatient clinics, antenatal clinics, and via VHT workers in community households. The procedures for each trial include PrEP/PEP counseling and services, choice of service location, HIV testing options, option for longer PrEP refills, provision of a clinical officer's or nurse's mobile telephone number for immediate PEP starts any day of the week, assessment of PrEP/PEP barriers and personalized actions, psychologic supports for traumatic experiences, and offer of concurrent, additional health or prevention related services. | 487 |
| Standard of Care The standard of care for PEP or PrEP differs according to each country's guidelines.
Standard of Care: The standard of care differs according to country but does not routinely offer PEP or PrEP to clients seeking services, does not offer choice of service location, HIV testing option or access to medical provider mobile phone number. | 497 |
| Total | 984 |
Baseline characteristics
| Characteristic | Standard of Care | Dynamic Choice Prevention (Including CAB LA) | Total |
|---|---|---|---|
| Age, Customized Age 15-24 | 159 Participants | 139 Participants | 298 Participants |
| Age, Customized Age >=25 | 338 Participants | 348 Participants | 686 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 497 Participants | 487 Participants | 984 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Kenya | 258 participants | 245 participants | 503 participants |
| Region of Enrollment Uganda | 239 participants | 242 participants | 481 participants |
| Sex: Female, Male Female | 358 Participants | 358 Participants | 716 Participants |
| Sex: Female, Male Male | 139 Participants | 129 Participants | 268 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 487 | 2 / 497 |
| other Total, other adverse events | 0 / 487 | 0 / 497 |
| serious Total, serious adverse events | 4 / 487 | 2 / 497 |
Outcome results
Primary
Biomedical Prevention Covered Time
Number of days participant taking biomedical prevention divided by number of days participant biomedical prevention use measured. Biomedical prevention includes PrEP tenofovir disoproxil fumarate/lamivudine (TDF/3TC) or cabotegravir long-acting injectable (CAB-LA) and PEP
Time frame: 48 weeks
Population: Study Participants at Week 48 with data on biomedical HIV prevention coverage during follow-up of the extension
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Dynamic Choice Prevention (Including CAB LA) | Biomedical Prevention Covered Time | 69.7 % of days |
| Standard of Care | Biomedical Prevention Covered Time | 13.3 % of days |
Secondary
Biomedical Prevention During Periods of Self Assessed HIV Risk
Number of months participant taking biomedical prevention and at self-assessed risk of HIV infection divided by number of months measured and at risk self-assessed risk of HIV infection
Time frame: 96 weeks
Secondary
HIV Incident Infection
HIV incidence rate: number of HIV incident infections divided by number at risk (HIV incidence per 100 person-years)
Time frame: 48 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dynamic Choice Prevention (Including CAB LA) | HIV Incident Infection | 0 infections per 100 person-years |
| Standard of Care | HIV Incident Infection | 1.8 infections per 100 person-years |
Secondary
HIV Incident Infection
HIV incidence rate: number of HIV incident infections divided by person time follow-up
Time frame: 96 weeks