The past decade has witnessed remarkable progress in the scale-up of antiretroviral therapy (ART), yet access to optimal diagnosis, care, and treatment remains limited for many of the 2.1 million children living with perinatally-acquired HIV worldwide. Novel diagnostic technologies and antiretroviral drugs (ARVs) can address this treatment gap. Critical questions remain, however, about the most effective way to utilize these innovations for children in settings with very limited resources. For example, how should programs best introduce new point-of-care assays for infant HIV diagnosis, and what are the most effective and cost-effective approaches to roll out pediatric dolutegravir and other emerging ARVs? Where long-term data are limited, or traditional clinical studies are not feasible, computer-based microsimulation modeling can use existing data to inform decisions about how to achieve the best outcomes for children with HIV under constrained healthcare budgets. With NICHD R01 support (2014-2019), we developed the Cost-effectiveness of Preventing AIDS Complications (CEPAC)-Pediatric microsimulation model and have informed guidelines and decisions from the World Health Organization (WHO), the President's Emergency Plan for AIDS Relief (PEPFAR), and country Ministries of Health (MOHs). In the first 4 years of the initial award cycle, we have used microsimulation and cost- effectiveness analysis methods to publish 17 papers related to pediatric HIV prevention, diagnosis, and treatment. We now propose to broaden the scope of this work, expanding a multidisciplinary team with diverse expertise in pediatric HIV care, research, clinical policy, and cost-effectiveness, and adding Zimbabwe to the original focus countries of Cte d'Ivoire and South Africa. This will allow us to compare findings across three PEPFAR settings that encompass a wide and representative range of pediatric HIV epidemiology, clinical practice, and healthcare costs. We will also develop new model-based methods, including location-optimization models and regression-based metamodels that can be used by local program planners to examine emerging care and treatment approaches across the spectrum of pediatric HIV care. We propose two new specific aims: 1. To project the optimal placement and value of innovative diagnostic technologies for pediatric HIV, including point-of-care assays for infant HIV diagnosis. 2. To evaluate the most effective and cost-effective ways to implement new ARV guidelines and introduce new ARV formulations for children, including the planned rollout of dolutegravir. The goal of this proposal is to help clinicians, program planners, and policymakers at MOHs, WHO, and PEPFAR identify the optimal use of scarce resources to improve long-term health for children with HIV. Continuation and expansion of support for the CEPAC-Pediatric modeling program will allow us to develop and disseminate novel modeling methods and address critical, context-specific questions about how to make the best use of innovative new technologies and treatments for millions of children affected by HIV worldwide.

Public Health Relevance

Although early diagnosis of HIV and prompt initiation of antiretroviral therapy (ART) can dramatically reduce infant mortality, HIV diagnosis is often delayed by older and inefficient diagnostic technologies, and choice of ART regimens for children is limited by the lack of tolerable formulations appropriate for age and weight. New point-of-care diagnostic tests and better-tolerated ART regimens can address these challenges, but concerns about cost limit their uptake in many global settings. We propose to expand methods in computer modeling of pediatric HIV infection to identify the most effective and cost-effective strategies for the implementation of new technologies and medications to improve outcomes for children affected by HIV.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD079214-07
Application #
9996743
Study Section
Population and Public Health Approaches to HIV/AIDS Study Section (PPAH)
Program Officer
Majji, Sai Prasanna
Project Start
2014-07-01
Project End
2024-06-30
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
7
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02114
Neilan, Anne M; Cohn, Jennifer E; Lemaire, Jean-Francois et al. (2018) HIV Testing After a First Positive Rapid Diagnostic Test: A Role for Nucleic Acid Testing? Open Forum Infect Dis 5:ofy170
Ciaranello, Andrea; Sohn, Annette H; Collins, Intira Jeannie et al. (2018) Simulation Modeling and Metamodeling to Inform National and International HIV Policies for Children and Adolescents. J Acquir Immune Defic Syndr 78 Suppl 1:S49-S57
Mallampati, Divya; MacLean, Rachel L; Shapiro, Roger et al. (2018) Optimal breastfeeding durations for HIV-exposed infants: the impact of maternal ART use, infant mortality and replacement feeding risk. J Int AIDS Soc 21:e25107
Neilan, Anne M; Dunville, Richard; Ocfemia, M Cheryl BaƱez et al. (2018) The Optimal Age for Screening Adolescents and Young Adults Without Identified Risk Factors for HIV. J Adolesc Health 62:22-28
Dunning, Lorna; Kroon, Max; Fourie, Lezanne et al. (2017) Impact of Birth HIV-PCR Testing on the Uptake of Follow-up Early Infant Diagnosis Services in Cape Town, South Africa. Pediatr Infect Dis J 36:1159-1164
Mahy, Mary; Penazzato, Martina; Ciaranello, Andrea et al. (2017) Improving estimates of children living with HIV from the Spectrum AIDS Impact Model. AIDS 31 Suppl 1:S13-S22
Dunning, Lorna; Francke, Jordan A; Mallampati, Divya et al. (2017) The value of confirmatory testing in early infant HIV diagnosis programmes in South Africa: A cost-effectiveness analysis. PLoS Med 14:e1002446
Neilan, Anne M; Karalius, Brad; Patel, Kunjal et al. (2017) Association of Risk of Viremia, Immunosuppression, Serious Clinical Events, and Mortality With Increasing Age in Perinatally Human Immunodeficiency Virus-Infected Youth. JAMA Pediatr 171:450-460
Francke, Jordan A; Penazzato, Martina; Hou, Taige et al. (2016) Clinical Impact and Cost-effectiveness of Diagnosing HIV Infection During Early Infancy in South Africa: Test Timing and Frequency. J Infect Dis 214:1319-1328
Myer, Landon; Phillips, Tamsin K; Zerbe, Allison et al. (2016) Optimizing Antiretroviral Therapy (ART) for Maternal and Child Health (MCH): Rationale and Design of the MCH-ART Study. J Acquir Immune Defic Syndr 72 Suppl 2:S189-96

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