Clinical trial NCT05549726: SEARCH CAB LA Dynamic Choice HIV Prevention Study Extension
Official title: A Multisectoral Strategy to Address Persistent Drivers of the HIV Epidemic in East Africa: SEARCH CAB LA Dynamic Choice HIV Prevention Study Extension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV
Keywords: Cabotegravir Injectable Suspension
PrEP
HIV Treatment and Prevention
Community Health
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Infectious Diseases Research Collaboration, Uganda
name: Makerere University
name: Kenya Medical Research Institute
name: University of California, Berkeley
name: National Institute of Allergy and Infectious Diseases (NIAID)
name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
name: National Institute of Mental Health (NIMH)
name: National Heart, Lung, and Blood Institute (NHLBI)
name: ViiV Healthcare
name: University of Pittsburgh
First posted: 2022-09-22
Enrollment: 984
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Exclusion Criteria:

Exclusion criteria to access CAB-LA as a prevention option:

1. Participant has Hepatitis B or chronic Hepatitis C Diagnosis
2. Participant has ALT \>=5x ULN
3. Participant has clinical history of liver cirrhosis or current clinical evidence of cirrhosis
4. Previous hypersensitivity reaction to cabotegravir
5. Receiving the following co-administered drugs for which significant decreases in cabotegravir plasma concentrations may occur due to uridine diphosphate glucuronosyltransferase:

   i. Anticonvulsants: Carbamazepine, oxcarbazepine, phenobarbital, phenytoin ii. Antimycobacterials: Rifampin, rifapentine
6. Participants with a current or anticipated need for chronic systemic anticoagulation or a history of known or suspected bleeding disorder, including a history of prolonged bleeding, except for the use of anticoagulation for deep vein thrombosis (DVT) prophylaxis (e.g., postoperative DVT prophylaxis) or the use of low dose acetylsalicylic acid (≤325 mg).

Primary outcomes:
measure: Biomedical Prevention Covered Time
timeFrame: 48 weeks
Secondary outcomes:
measure: HIV Incident Infection
timeFrame: 48 weeks
measure: HIV Incident Infection
timeFrame: 96 weeks
measure: Biomedical Prevention During Periods of Self Assessed HIV Risk
timeFrame: 96 weeks
Other outcomes:
Locations:
city: Kisumu
country: Kenya
facility: GPRT / SEARCH Office
city: Mbarara
country: Uganda
facility: IDRC Southwest Uganda
Study officials:
affiliation: University of California, San Francisco
name: Diane Havlir, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Makerere University
name: Moses Kamya, MBChB, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Berkeley
name: Maya Petersen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: