Several studies show that Adolescents and Young Adults (AYA) have poor outcomes along the entire Human Immunodeficiency Virus (HIV) prevention and care cascades compared to adults. The investigators propose to evaluate novel evidence-based HIV prevention and care interventions (including Cabotegravir LongActing (CABLA) to determine implementation outcomes among AYA who are at particularly high risk for HIV acquisition and poor viral suppression in five geographically distinct research performance sites in Uganda. The results will provide important evidence to inform Uganda and other regional countries' policy on integrated HIV prevention, care and treatment for AYA at high risk for HIV and Sexually Transmitted Infections (STIs) in order to reach the UNAIDS 95-95-95 targets and HIV epidemic control.

Adolescents and Young Adults (AYA) have a high HIV incidence and poor outcomes along the entire HIV prevention and care cascades compared to adults. Despite the high HIV burden, both uptake of oral Pre-Exposure Prophylaxis (PrEP) (HIV negatives) and achieving viral suppression (HIV positives) are sub-optimal among youth in Sub-Saharan Africa. Among youth in Uganda, uptake and persistence on oral PrEP is low, with reasons for discontinuation including: pill burden, low perceived severity of HIV, need for partner or parental approval, HIV-related stigma, fear of side-effects and health facility barriers. Cabotegravir, a is new long-acting antiretroviral (CABLA) and highly efficacious PrEP choice that can mitigate barriers to use of daily oral PrEP. The Investigators propose to evaluate evidence-based HIV prevention and care interventions to improve implementation outcomes among high-risk AYA (15-24 years) in Uganda. The study covers the continuum of care, will use novel screening methods for HIV risk, will involve teams that are highly experienced in youth-focused clinical trials and Implementation Science (ImS), will implement Ministry of Health (MOH) approved community differentiated service delivery models for delivery CABLA, will evaluate the implementation of the Sustainable East Africa Research in Community Health (SEARCH) -Youth (SY), a multi-component intervention comprising of life-stage based assessment and support to increase viral suppression in high-risk AYA with HIV, and will use hybrid effectiveness implementation designs to assess these evidence-based interventions. The aims include: Aim 1: Using the Consolidated Framework for Implementation Research (CFIR), the investigators will identify determinants of potential implementation success of two innovations: CABLA and SY implementation at the community, clinic, provider, and patient levels in 5 geographically distinct sites in Uganda. Aim 2a: Using a hybrid effectiveness implementation type II design, the investigators will assess the uptake and persistence of CAB-LA. The investigators will conduct a randomized prospective study to assess effectiveness for the provision of CABLA among high risk AYA. Effectiveness outcome will be proportion of study subjects who have initiated CABLA and persisted at 18 months of follow-up comparing facility and community delivery options. Implementation outcomes will be feasibility, acceptability, adoption and maintenance using Reach Effectiveness Adoption Implementation Maintenance (REAIM). Aim 2b: Using a hybrid effectiveness implementation type III design the investigators will assess implementation (feasibility, adoption, fidelity, and sustainment) and effectiveness of the SY intervention in increasing long-term virologic suppression (<200 c/mL) at 18 months of follow-up in 5 Clinical Research Performance Sites (CRPS) using REAIM. Aim 3: The investigators will use platforms in aims 1 and 2 to strengthen capacity of ImS and to translate findings into policy and guidelines. The study involves solid community and institutional partnerships and builds on a strong multi-disciplinary team highly experienced in innovative methods and implementation science in sub-Saharan Africa. The project, building on Prevention and Treatment through a Comprehensive Care Continuum for HIV-affected Adolescents in Resource Constrained Settings Implementation Science Network (PATC3H) and Adolescent HIV prevention and treatment implementation Science Alliance (AHISA), is responsive to World Health Organization's, Uganda's MoH priorities regarding the gap in HIV services for highly vulnerable AYA. It will test a novel, scalable and integrated approach to initiate and sustain support for high-risk AYA in Low and Middle Income Countries (LMICs).

Adolescents and young adults with increased likelihood of HIV acquisition

• AYA 15 to 24 years of age
• Classified as high risk using our screening tool.
• Documented HIV un-infected as per the national HIV testing algorithm.
• Willing to use PrEP
• Willing to provide written informed consent.
• No plans to relocate permanently in the next 6 months
• No suspicion of acute HIV infection:
• Hepatitis B virus surface antigen (HBsAg)-negative and accepts HB vaccination
• Having no medical or social condition that, in the opinion of the study investigator, would interfere with the conduct of the study or interpretation of study results.
• HIV-uninfected, based on HIV test results obtained at screening and enrolment visit and just prior to randomization. All HIV test results must be obtained and must all be negative/non-reactive according to national HIV testing algorithm. Adolescents and young adults living with HIV
• AYA 15-24 years' old
• Willing to receive ART at participating health facilities
• Have high-risk characteristics for viral load non-suppression, such as missed visits, disengagement from care, new to care, and non-suppressed viral load (VL) on the last VL testing.
• Willing to provide written informed consent.
• No plans to relocate permanently in the next 6 months
• Having no medical or social condition that, in the opinion of the study investigator, would interfere with the conduct of the study or interpretation of study results

Exclusion Criteria:

Adolescents and young adults with increased likelihood of HIV acquisition

• One or more reactive HIV test results at Screening or Enrollment, even if HIV infection is not confirmed.
• Has a cognitive impairment that prevents understanding of study procedures and precludes informed consent.
• Plan to move out of the greater study catchment area during study period.
• Enrolled in another intervention study.
• Already on PrEP.
• Unwilling or unable to commit to using CAB LA
• Ineligible to initiate CAB-LA as per the Uganda national PrEP guidelines
• Hepatotoxicity and or Hepatitis B infection
• Potential exposure to HIV in past 72 hours
• Signs/symptoms of acute HIV infection
• Current or chronic history of liver disease or known hepatic/biliary abnormalities, history of seizure disorder, clinically significant cardiovascular disease, coagulopathy, and inflammatory skin conditions, as defined in Human Subjects Protection document. (Cabotegravir IB or package insert)
• Hypersensitivity to any active substances or other substances in CAB-LA
• Allergic or hypersensitivity reaction(s) with previous use of CAB or other integrase inhibitor medications Adolescents and young adults living with HIV
• Not able to give written informed consent.
• Not receiving care in selected facilities