Programs to promptly diagnose and treat pediatric HIV infection play a critical role in reducing childhood mortality in sub-Saharan Africa. Clinical leaders and policymakers need to understand the long-term benefits and costs of these programs, which may differ in settings with different types of HIV epidemics. South Africa is a middle-income country with a very high HIV prevalence (30%: a generalized HIV epidemic) and excellent access to health services for HIV-infected women and their infants. C?te d'Ivoire is a low-income country with a lower HIV prevalence (3%: a mixed HIV epidemic) and more limited access to HIV-related health services. These two countries represent two of the key types of HIV epidemic in sub-Saharan Africa. The long-term outcomes of pediatric HIV treatment reflect a continuum of events over decades, and thus cannot be fully investigated using traditional methodologies, such as clinical trials or cohort studies. Computer models can add great value to shorter-term clinical studies by projecting survival and healthcare resource utilization over both short and long time horizons; this can assist clinicians and policymakers in prioritizing among many competing demands for limited resources. In addition, computer models can identify factors that will have the greatest influence on survival and costs, and thus outline critical priorities for future research. Through K01 AI078754 and the IMPAACT network, NICHD, NIAID, and NIMH have supported a preliminary model of pediatric HIV disease, the Cost-effectiveness of Preventing AIDS Complications (CEPAC)-Pediatric model. We have assembled an international research team with expertise in pediatric HIV, simulation modeling, and epidemiology, and we have used the CEPAC-Pediatric model to conduct analyses of strategies to prevent pediatric HIV infection that have informed WHO guidelines. We now propose a major expansion of the CEPAC-Pediatric model and the use of our model to evaluate novel strategies to diagnose and treat pediatric HIV in South Africa and C?te d'Ivoire. Our three specific aims are: 1) to determine the most effective and efficient strategies for early infant HIV diagnosis; 2) to investigate the clinical outcomes and cost- effectiveness of HIV treatment initiation strategies for children; and 3) to project the clinical and economic outcomes of strategies for monitoring 1st-line therapy and switching to 2nd-line therapy for HIV-infected children. By reflecting key comparisons between South Africa and C?te d'Ivoire, these analyses will represent many of the clinical and economic conditions that characterize the HIV epidemic in Africa. The project's goals to reduce HIV-related morbidity and mortality align with the mission of NICHD: to ensure that all children have the chance to achieve their full potential for healthy and productive lives, free from disease or disability. The project further meets key goals of the Office of AIDS Research, the PEPFAR Roadmap for Saving Lives, and Millennium Development Goals 6 and 4: to prioritize research for women and vulnerable children, to ensure universal access to HIV treatment for children, and to reduce under-five mortality worldwide.

Public Health Relevance

Worldwide, 1.4 million children are born to HIV-infected women, and over 300,000 infants are infected with HIV each year. Early diagnosis of HIV infection in infants and prompt initiation of antiretroviral therapy (ART) can dramatically reduce mortality, but access to early HIV diagnosis and ART remains very limited due to problems of feasibility, costs, and competing public health demands. We propose to develop novel approaches in computer modeling of infant HIV infection that will incorporate these benefits and challenges; this will enable us to determine the most effective way to expand programs to diagnose and treat pediatric HIV infection in resource-limited settings.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD079214-04
Application #
9306891
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Hazra, Rohan
Project Start
2014-07-01
Project End
2019-06-30
Budget Start
2017-07-01
Budget End
2018-06-30
Support Year
4
Fiscal Year
2017
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
Walensky, Rochelle P; Borre, Ethan D; Bekker, Linda-Gail et al. (2016) The Anticipated Clinical and Economic Effects of 90-90-90 in South Africa. Ann Intern Med 165:325-33
Desmonde, Sophie; Avit, Divine; Petit, Junie et al. (2016) Costs of Care of HIV-Infected Children Initiating Lopinavir/Ritonavir-Based Antiretroviral Therapy before the Age of Two in Cote d'Ivoire. PLoS One 11:e0166466

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