Model-Based Methods to Translate Adolescent Medicine Trials Network for HIV/AIDS Interventions Findings Into Policy Recommendations: Rationale and Protocol for a Modeling Core (ATN 161)

Background The United States Centers for Disease Control and Prevention estimates that approximately 60,000 US youth are living with HIV. US youth living with HIV (YLWH) have poorer outcomes compared with adults, including lower rates of diagnosis, engagement, retention, and virologic suppression. With Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) support, new trials of youth-centered interventions to improve retention in care and medication adherence among YLWH are underway. Objective This study aimed to use a computer simulation model, the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)-Adolescent Model, to evaluate selected ongoing and forthcoming ATN interventions to improve viral load suppression among YLWH and to define the benchmarks for uptake, effectiveness, durability of effect, and cost that will make these interventions clinically beneficial and cost-effective. Methods This protocol, ATN 161, establishes the ATN Modeling Core. The Modeling Core leverages extensive data—already collected by successfully completed National Institutes of Health–supported studies—to develop novel approaches for modeling critical components of HIV disease and care in YLWH. As new data emerge from ongoing ATN trials during the award period about the effectiveness of novel interventions, the CEPAC-Adolescent simulation model will serve as a flexible tool to project their long-term clinical impact and cost-effectiveness. The Modeling Core will derive model input parameters and create a model structure that reflects key aspects of HIV acquisition, progression, and treatment in YLWH. The ATN Modeling Core Steering Committee, with guidance from ATN leadership and scientific experts, will select and prioritize specific model-based analyses as well as provide feedback on derivation of model input parameters and model assumptions. Project-specific teams will help frame research questions for model-based analyses as well as provide feedback regarding project-specific inputs, results, sensitivity analyses, and policy conclusions. Results This project was funded as of September 2017. Conclusions The ATN Modeling Core will provide critical information to guide the scale-up of ATN interventions and the translation of ATN data into policy recommendations for YLWH in the United States.

[1]  Sung-Jae Lee,et al.  Barriers and Facilitators to the Collection and Aggregation of Electronic Health Record HIV Data: An Analysis of Study Recruitment Venues Within the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) , 2021, Evaluation & the health professions.

[2]  R. Bolan,et al.  Acute HIV Infection in Youth: Protocol for the Adolescent Trials Network 147 (ATN147) Comprehensive Adolescent Research and Engagement Studies (CARES) Study , 2019, JMIR research protocols.

[3]  S. Goodreau,et al.  Potential Impact of HIV Preexposure Prophylaxis Among Black and White Adolescent Sexual Minority Males , 2018, American journal of public health.

[4]  Travis Sanchez,et al.  University of North Carolina/Emory Center for Innovative Technology (iTech) for Addressing the HIV Epidemic Among Adolescents and Young Adults in the United States: Protocol and Rationale for Center Development , 2018, JMIR research protocols.

[5]  Вестник КемГУ Network , 2018, Definitions.

[6]  A. Sohn,et al.  Simulation Modeling and Metamodeling to Inform National and International HIV Policies for Children and Adolescents , 2018, Journal of acquired immune deficiency syndromes.

[7]  Matthew A Psioda,et al.  Adolescent Medicine Trials Network for HIV/AIDS Interventions Data Harmonization: Rationale and Development of Guidelines , 2018, JMIR research protocols.

[8]  J. Parsons,et al.  Adolescent Trials Network for HIV-AIDS Scale It Up Program: Protocol for a Rational and Overview , 2018, JMIR research protocols.

[9]  J. Sleasman,et al.  Sexually transmitted infections and immune activation among HIV-infected but virally suppressed youth on antiretroviral therapy. , 2018, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[10]  J. Bauermeister,et al.  Interaction Effects of Neighborhood Disadvantage and Individual Social Support on Frequency of Alcohol Use in Youth Living with HIV , 2018, American journal of community psychology.

[11]  S. Goodreau,et al.  Targeting Human Immunodeficiency Virus Pre-Exposure Prophylaxis to Adolescent Sexual Minority Males in Higher Prevalence Areas of the United States: A Modeling Study. , 2017, The Journal of adolescent health : official publication of the Society for Adolescent Medicine.

[12]  L. Myer,et al.  Impact of Birth HIV-PCR Testing on the Uptake of Follow-up Early Infant Diagnosis Services in Cape Town, South Africa , 2017, The Pediatric infectious disease journal.

[13]  R. Walensky,et al.  The value of confirmatory testing in early infant HIV diagnosis programmes in South Africa: A cost-effectiveness analysis , 2017, PLoS medicine.

[14]  J. Fortenberry,et al.  HIV Continuum of Care for Youth in the United States , 2017, Journal of acquired immune deficiency syndromes.

[15]  Paige L. Williams,et al.  Association of Risk of Viremia, Immunosuppression, Serious Clinical Events, and Mortality With Increasing Age in Perinatally Human Immunodeficiency Virus–Infected Youth , 2017, JAMA pediatrics.

[16]  H. Gendelman,et al.  Long-acting slow effective release antiretroviral therapy , 2017, Expert opinion on drug delivery.

[17]  J. Murray,et al.  Decreased PD-1 Expression on CD8 Lymphocyte Subsets and Increase in CD8 Tscm Cells in Children with HIV Receiving Raltegravir. , 2016, AIDS research and human retroviruses.

[18]  Paige L. Williams,et al.  Sexually Transmitted Infections in Youth With Controlled and Uncontrolled Human Immunodeficiency Virus Infection , 2016, Journal of the Pediatric Infectious Diseases Society.

[19]  John Brazier,et al.  Nothing About Us Without Us? A Comparison of Adolescent and Adult Health-State Values for the Child Health Utility-9D Using Profile Case Best-Worst Scaling. , 2016, Health economics.

[20]  M. Bertram,et al.  The Case for Adolescent HIV Vaccination in South Africa , 2016, Medicine.

[21]  S. Spector,et al.  Pharmacokinetics and 48-Week Safety and Efficacy of Raltegravir for Oral Suspension in Human Immunodeficiency Virus Type-1-Infected Children 4 Weeks to 2 Years of Age. , 2015, Journal of the Pediatric Infectious Diseases Society.

[22]  E. Acosta,et al.  Safety, Pharmacokinetics and Efficacy of Dolutegravir in Treatment-experienced HIV-1 Infected Adolescents: Forty-eight-week Results from IMPAACT P1093 , 2015, The Pediatric infectious disease journal.

[23]  J. Brazier,et al.  Valuing Child Health Utility 9D Health States with Young Adults: Insights from a Time Trade Off Study , 2015, Applied Health Economics and Health Policy.

[24]  Paige L. Williams,et al.  Psychiatric symptoms and antiretroviral nonadherence in US youth with perinatal HIV: a longitudinal study , 2015, AIDS.

[25]  M. Weinstein,et al.  Cost-effectiveness of first-line antiretroviral therapy for HIV-infected African children less than 3 years of age , 2015, AIDS.

[26]  J. Bauermeister,et al.  Rates and Correlates of Antiretroviral Therapy Use and Virologic Suppression Among Perinatally and Behaviorally HIV-Infected Youth Linked to Care in the United States , 2015, Journal of acquired immune deficiency syndromes.

[27]  Richard D Moore,et al.  The Lifetime Medical Cost Savings From Preventing HIV in the United States , 2015, Medical care.

[28]  Joshua T. Cohen,et al.  Updating cost-effectiveness--the curious resilience of the $50,000-per-QALY threshold. , 2014, The New England journal of medicine.

[29]  R. Walensky,et al.  Individualizing the WHO HIV and infant feeding guidelines: optimal breastfeeding duration to maximize infant HIV-free survival , 2014, AIDS.

[30]  Brian C. Zanoni,et al.  The adolescent and young adult HIV cascade of care in the United States: exaggerated health disparities. , 2014, AIDS patient care and STDs.

[31]  S. Spector,et al.  Pharmacokinetics, safety, and 48-week efficacy of oral raltegravir in HIV-1-infected children aged 2 through 18 years. , 2014, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[32]  C. Delaugerre,et al.  French 2013 guidelines for antiretroviral therapy of HIV-1 infection in adults , 2014, Journal of the International AIDS Society.

[33]  M. Weinstein,et al.  Validation and Calibration of a Computer Simulation Model of Pediatric HIV Infection , 2013, PloS one.

[34]  M. Weinstein,et al.  Cost-effectiveness of HIV treatment as prevention in serodiscordant couples. , 2013, The New England journal of medicine.

[35]  J. Caro,et al.  Model transparency and validation: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force--7. , 2012, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[36]  Jonathan Karnon,et al.  Model Parameter Estimation and Uncertainty Analysis , 2012, Medical decision making : an international journal of the Society for Medical Decision Making.

[37]  William Hollingworth,et al.  Model Transparency and Validation , 2012, Medical decision making : an international journal of the Society for Medical Decision Making.

[38]  Jonathan Karnon,et al.  Model Parameter Estimation and Uncertainty: a Report of the Ispor-smdm Modeling Good Research Practices Task Force-6 Background to the Task Forcemodel-parameter-estimation-and- Uncertainty-analysis.asp). a Summary of These Articles Was Pre- Sented at a Plenary Session at the Ispor 16th Annual Intern , 2022 .

[39]  J. Sleasman,et al.  Substantial multiclass transmitted drug resistance and drug-relevant polymorphisms among treatment-naïve behaviorally HIV-infected youth. , 2012, AIDS patient care and STDs.

[40]  R. Walensky,et al.  WHO 2010 Guidelines for Prevention of Mother-to-Child HIV Transmission in Zimbabwe: Modeling Clinical Outcomes in Infants and Mothers , 2011, PloS one.

[41]  Matthias Egger,et al.  Sexual transmission of HIV according to viral load and antiretroviral therapy: systematic review and meta-analysis , 2009, AIDS.

[42]  S. Reisner,et al.  A review of HIV antiretroviral adherence and intervention studies among HIV-infected youth. , 2009, Topics in HIV medicine : a publication of the International AIDS Society, USA.

[43]  John D Seeger,et al.  Long-term effectiveness of highly active antiretroviral therapy on the survival of children and adolescents with HIV infection: a 10-year follow-up study. , 2008, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[44]  Daniel S. Nagin,et al.  Advances in Group-Based Trajectory Modeling and an SAS Procedure for Estimating Them , 2007 .

[45]  Milton C Weinstein,et al.  Cost-Effectiveness of an Intervention to Improve Adherence to Antiretroviral Therapy in HIV-Infected Patients , 2006, Journal of acquired immune deficiency syndromes.

[46]  J. Lindsey,et al.  Immune reconstitution and predictors of virologic failure in adolescents infected through risk behaviors and initiating HAART: week 60 results from the PACTG 381 cohort. , 2006, AIDS research and human retroviruses.

[47]  M. Rotheram-Borus,et al.  Cost-effectiveness of a behavioral intervention for seropositive youth. , 2005, AIDS education and prevention : official publication of the International Society for AIDS Education.

[48]  J. Coast,et al.  Quality-Adjusted Life-Years Lack Quality in Pediatric Care: A Critical Review of Published Cost-Utility Studies in Child Health , 2005, Pediatrics.

[49]  Milton C Weinstein,et al.  Expanded screening for HIV in the United States--an analysis of cost-effectiveness. , 2005, The New England journal of medicine.

[50]  Milton C Weinstein,et al.  Projecting the cost-effectiveness of adherence interventions in persons with human immunodeficiency virus infection. , 2003, The American journal of medicine.

[51]  Richard D Moore,et al.  Rapid Communication Hospital and Outpatient Health Services Utilization Among HIV‐Infected Patients in Care in 1999 , 2002, Journal of acquired immune deficiency syndromes.

[52]  T J Ulahannan,et al.  Decision Making in Health and Medicine: Integrating Evidence and Values , 2002 .

[53]  S. Kegeles,et al.  Cost-effectiveness of the Mpowerment Project, a community-level intervention for young gay men. , 2001 .

[54]  M C Weinstein,et al.  The cost effectiveness of combination antiretroviral therapy for HIV disease. , 2001, The New England journal of medicine.

[55]  K. Roeder,et al.  A SAS Procedure Based on Mixture Models for Estimating Developmental Trajectories , 2001 .

[56]  David R. Holtgrave,et al.  Economic Evaluation of HIV Risk Reduction Intervention in African‐American Male Adolescents , 2000, Journal of acquired immune deficiency syndromes.

[57]  P D Cleary,et al.  Health-related quality of life in patients with human immunodeficiency virus infection in the United States: results from the HIV Cost and Services Utilization Study. , 2000, The American journal of medicine.

[58]  C. Sherbourne,et al.  Impact of psychiatric conditions on health-related quality of life in persons with HIV infection. , 2000, The American journal of psychiatry.

[59]  M C Weinstein,et al.  The cost-effectiveness of preventing AIDS-related opportunistic infections. , 1998, JAMA.

[60]  M. Weinstein,et al.  Recommendations of the Panel on Cost-effectiveness in Health and Medicine. , 1996, JAMA.

[61]  Anne S Frankel,et al.  National Institutes of Health , 2019, The Grants Register 2022.

[62]  R. Walensky,et al.  The Optimal Age for Screening Adolescents and Young Adults Without Identified Risk Factors for HIV. , 2018, The Journal of adolescent health : official publication of the Society for Adolescent Medicine.

[63]  W. Cleveland,et al.  Locally Weighted Regression: An Approach to Regression Analysis by Local Fitting , 1988 .

[64]  G. Tao,et al.  Economic evaluation of an HIV prevention intervention for gay and bisexual male adolescents. , 1998, Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association.

[65]  Takuji Nishimura,et al.  Mersenne twister: a 623-dimensionally equidistributed uniform pseudo-random number generator , 1998, TOMC.