PROJECT SUMMARY Despite substantial progress in preventing infant HIV infections, an estimated 160,000 new pediatric infections still occur each year worldwide, primarily due to gaps in testing and care for pregnant and lactating people with HIV. The World Health Organization (WHO) and UNAIDS have issued an ambitious call to end pediatric HIV by 2030. With NICHD support, R01HD079214 has launched development and growth of the CEPAC-Pediatric model, a detailed microsimulation model of HIV in children in Côte d'Ivoire, South Africa, and Zimbabwe. CEPAC-P analyses focused on diagnosis and treatment of HIV have been cited in every published WHO HIV Guideline since 2013. In the next award cycle, we propose to address the crucial question: what will it take to drive infant HIV infections as close to zero as possible? Meeting this ambitious goal will require not only pediatric interventions, such as improved postnatal prophylaxis for infants born to people with HIV, but also bold and creative interventions for pregnant and lactating people with or at risk for HIV to prevent, diagnose, and treat maternal HIV before infant infection occurs. Both pediatric and maternal interventions are needed, but neither can be considered in isolation; the choice of maternal interventions will determine what infant interventions are clinically most useful and provide good economic value. We will conduct CEPAC model- based policy analyses of individual maternal and infant interventions. We will then develop, test, and apply simulation optimization methods to identify the package of these interventions that minimizes infant infection risk, improves infant and maternal health, and provides the best value for limited healthcare resources in each of the three focus countries described above. Our Specific Aims include: Aim 1: To estimate the clinical outcomes and cost-effectiveness of maternal HIV testing, prevention, and treatment approaches to reduce vertical HIV transmission and improve maternal health Aim 2: To identify the most effective and cost-effective infant HIV prophylaxis and testing strategies Aim 3: To optimize integrated maternal-child HIV prevention and treatment approaches To make the findings of this work more broadly applicable, we will identify optimal packages of care in three WHO-defined country “types,” based on HIV incidence, prevalence, and access to care. To make the findings accessible to clinicians, program planners, and policymakers, we will develop optimization webtools for different settings. This proposal leverages the substantial advances in pediatric HIV simulation modeling made by the CEPAC-P team in the prior cycle to address the full range of approaches that will be needed to achieve ambitious global goals of eliminating pediatric AIDS. This work directly addresses NICHD research priorities: “efficient use of next-generation preventive and therapeutic technologies and prevention of HIV acquisition and illness in women and infants.” It al...