An interactive tool for designing efficient toxicology experiments.

The design of dose-response experiments is an important part of toxicology research. Efficient design of these experiments requires choosing optimal doses and assigning the correct number of subjects to those doses under a given criterion. Optimal design theory provides the tools to find the most efficient experimental designs in terms of cost and statistical efficiency. However, the mathematical details can be distracting and make these designs inaccessible to many toxicologists. To facilitate use of these designs, we present an easy to use web-app for finding two types of optimal designs for models commonly used in toxicology. We include tools for checking the optimality of a given design and for assessing efficiency of any user-supplied design. Using state-of-the-art nature-inspired metaheuristic algorithms, the web-app allows the user to quickly find optimal designs for estimating model parameters or the benchmark dose.

Factors Associated With Antiretroviral Adherence Among Youth Living With HIV.

BACKGROUND: Youth living with HIV (YLH) have an increased risk for psychosocial stressors that can affect their antiretroviral (ARV) adherence. We examined factors associated with self-reported ARV adherence among YLH ages 12-24 years old. SETTING: YLH (N = 147) were recruited in Los Angeles, CA, and New Orleans, LA from 2017 to 2020. METHODS: YLH whose self-reported recent (30 days) ARV adherence was "excellent" or "very good" were compared with nonadherent YLH on sociodemographic, clinical, and psychosocial factors using univariate and multivariate analyses. RESULTS: Participants were predominantly male (88%), and 81% identified as gay, bisexual, transgender, queer, or other. The mean duration on ARV was 27 months (range 0-237 months). Most YLH (71.2%) self-reported being adherent, and 79% of those who self-reported adherence were also virally suppressed (<200 copies/mL). Multivariate analysis indicated being adherent was significantly associated with white race [aOR = 8.07, confidence intervals (CI): 1.45 to 74.0], Hispanic/Latinx ethnicity [aOR = 3.57, CI: 1.16 to 12.80], more social support [aOR = 1.11, CI: 1.05 to 1.18], and being on ARV for a shorter duration [aOR = 0.99, CI: 0.97 to 0.99]. Mental health symptoms, substance use, age, and history of homelessness or incarceration were unrelated to adherence. CONCLUSIONS: Enhancing efforts to provide support for adherence to non-white youth, and those with limited social support and who have been on ARV treatment longer, may help increase viral suppression among YLH.

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.