Optimal strategies to improve uptake of and adherence to HIV prevention among young people at risk for HIV acquisition in the USA (ATN 149): a randomised, controlled, factorial trial.

BACKGROUND: Pre-exposure prophylaxis (PrEP), condom use, post-exposure prophylaxis (PEP), and sexual partner reduction help to prevent HIV acquisition but have low uptake among young people. We aimed to assess the efficacy of automated text messaging and monitoring, online peer support, and strengths-based telehealth coaching to improve uptake of and adherence to PrEP, condom use, and PEP among adolescents aged 12-24 years at risk of HIV acquisition in Los Angeles, CA, USA, and New Orleans, LA, USA. METHODS: We conducted a four-arm randomised controlled factorial trial, assessing interventions designed to support uptake and adherence of HIV prevention options (ie, PrEP, PEP, condom use, and sexual partner reduction). We recruited young people aged 12-24 years who were at risk of HIV acquisition from 13 community-based organisations, adolescent medicine clinics, and organisations serving people who are unstably housed, people who were previously incarcerated, and other vulnerable young people, and through dating apps, peer referrals, and social venues and events in Los Angeles, CA, USA, and New Orleans, LA, USA. Young people who tested seronegative and reported being gay, bisexual, or other men who have sex with men, transgender men or women, or gender diverse (eg. non-binary or genderqueer) were eligible for inclusion. Participants were randomly assigned to one of four intervention groups in a factorial design: automated text messaging and monitoring (AMMI) only, AMMI plus peer support via private social media, AMMI plus strengths-based telehealth coaching by near-peer paraprofessionals, or AMMI plus peer support and coaching. Assignment was further stratified by race or ethnicity and sexual orientation within each interviewer's group of participants. Participants were masked to intervention assignment until after baseline interviews when offered their randomly assigned intervention, and interviewers were masked throughout the study. Interventions were available throughout the 24-month follow-up period, and participants completed baseline and follow-up assessments, including rapid diagnostic tests for sexually transmitted infections, HIV, and substance use, at 4-month intervals over 24 months. The primary outcomes were uptake and adherence to HIV prevention options over 24 months, measured by self-reported PrEP use and adherence, consistent condom use with all partners, PEP prescription and adherence, and number of sexual partners in participants with at least one follow-up. We used Bayesian generalised linear modelling to assess changes in outcomes over time comparing the four study groups. This study is registered with ClinicalTrials.gov (NCT03134833) and is completed. FINDINGS: We screened 2314 adolescents beginning May 1, 2017, to enrol 1037 participants (45%) aged 16-24 years between May 6, 2017, and Aug 30, 2019, of whom 895 (86%) had follow-up assessments and were included in the analytical sample (313 assigned to AMMI only, 205 assigned to AMMI plus peer support, 196 assigned to AMMI plus coaching, and 181 assigned to AMMI plus peer support and coaching). Follow-up was completed on Nov 8, 2021. Participants were diverse in race and ethnicity (362 [40%] Black or African American, 257 [29%] Latinx or Hispanic, 184 [21%] White, and 53 [6%] Asian or Pacific Islander) and other sociodemographic factors. At baseline, 591 (66%) participants reported anal sex without a condom in the past 12 months. PrEP use matched that in young people nationally, with 101 (11%) participants reporting current PrEP use at baseline, increasing at 4 months to 132 (15%) and continuing to increase in the AMMI plus peer support and coaching group (odds ratio 2·31, 95% CI 1·28-4·14 vs AMMI control). There was no evidence for intervention effect on condom use, PEP use (ie, prescription or adherence), PrEP adherence, or sexual partner numbers. No unanticipated or study-related adverse events occurred. INTERPRETATION: Results are consistent with hypothesised synergistic intervention effects of evidence-based functions of informational, motivational, and reminder messaging; peer support for HIV prevention; and strengths-based, goal-focused, and problem-solving telehealth coaching delivered by near-peer paraprofessionals. These core functions could be flexibly scaled via combinations of technology platforms and front-line or telehealth HIV prevention workers. FUNDING: Adolescent Medicine Trials Network for HIV/AIDS Interventions, US National Institutes of Health.

Tunable three-dimensional architecture of nematic disclination lines.

Disclination lines play a key role in many physical processes, from the fracture of materials to the formation of the early universe. Achieving versatile control over disclinations is key to developing novel electro-optical devices, programmable origami, directed colloidal assembly, and controlling active matter. Here, we introduce a theoretical framework to tailor three-dimensional disclination architecture in nematic liquid crystals experimentally. We produce quantitative predictions for the connectivity and shape of disclination lines found in nematics confined between two thinly spaced glass substrates with strong patterned planar anchoring. By drawing an analogy between nematic liquid crystals and magnetostatics, we find that i) disclination lines connect defects with the same topological charge on opposite surfaces and ii) disclination lines are attracted to regions of the highest twist. Using polarized light to pattern the in-plane alignment of liquid crystal molecules, we test these predictions experimentally and identify critical parameters that tune the disclination lines' curvature. We verify our predictions with computer simulations and find nondimensional parameters enabling us to match experiments and simulations at different length scales. Our work provides a powerful method to understand and practically control defect lines in nematic liquid crystals.