SEARCH CAB LA Dynamic Choice HIV Prevention Study Extension

University of California, San Francisco984 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

Interventions

Cabotegravir Injectable SuspensionDRUG

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 ModelOTHER

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.

Standard of CareOTHER

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.

Eligibility

Sex: ALLMin age: 15 YearsHealthy volunteers:

Medical Language ↔ Plain English

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).

Outcomes

Primary Outcomes

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

Secondary Outcomes

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

HIV Incident Infection

HIV incidence rate: number of HIV incident infections divided by person time follow-up

Time frame: 96 weeks

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