SEARCH CAB LA Dynamic Choice HIV Prevention Study Extension

Phase 4

Completed

Interventions: Drug: Cabotegravir Injectable Suspension
Other: Standard of Care
Other: Dynamic Choice Delivery Model

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.

Recruitment & Eligibility

Inclusion Criteria

Inclusion criteria for the Extension include:

Additional inclusion criteria to access CAB-LA as a prevention option

Exclusion Criteria

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

Participant has Hepatitis B or chronic Hepatitis C Diagnosis
Participant has ALT >=5x ULN
Participant has clinical history of liver cirrhosis or current clinical evidence of cirrhosis
Previous hypersensitivity reaction to cabotegravir
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
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).

Arm && Interventions

Group	Intervention	Description
Dynamic choice prevention (including CAB LA)	Cabotegravir Injectable Suspension	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.
Dynamic choice prevention (including CAB LA)	Dynamic Choice Delivery Model	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.
Standard of Care	Standard of Care	The standard of care for PEP or PrEP differs according to each country's guidelines.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
HIV Incident Infection	96 weeks	HIV incidence rate: number of HIV incident infections divided by person time follow-up
Biomedical Prevention During Periods of Self Assessed HIV Risk	96 weeks	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