The K01 Mentored Research Scientist Development Award will provide the Candidate with the protected time to develop skills in implementation science, mathematical modeling of infectious diseases, and cost- effectiveness analysis, and use these skills in combination with robust epidemiological methodology to become an independent investigator focused on programmatic and public health approaches to HIV prevention for women. The Candidate's long-term objective is to become a global leader in HIV prevention and reproductive health, using implementation science and mathematical modeling to prioritize, design, implement, and evaluate evidence-based interventions, which will help transform public health programs, and guide policy. The proposed 5-year training plan will support the achievement of these objectives with the assistance of the outstanding, interdisciplinary research environment at the University of Washington (UW) and the Kenya Research Program, experienced mentors and advisors, and long-standing collaborations with Kenyan investigators. The training plan was carefully developed with the K01 mentors to include didactic coursework, mentored training, and scientific meetings to fill a gap in the Candidate's training, which will help her develop a unique combination of skills and experience. The mixture of formal training along with a two-tiered approach to mentorship, which includes two co-mentors and a mentoring team, were strategically designed to complete the research and career objectives during the award period and prepare the Candidate for an independent research career. The career goals to be achieved during the award period are: 1) gain knowledge and skills in implementation science and translational clinical research for HIV prevention; 2) develop skills in the construction and validation of mathematical models of infectious diseases to determine program and intervention impacts; 3) obtain practical skills in the conduct of costing and cost-effectiveness analysis, from programmatic and societal perspectives; 4) build the Candidate's research portfolio and publication record, generate data and scientific questions for a future R01, and transition the Candidate into an independent academic career. Research Plan: Risk of HIV acquisition during pregnancy and postpartum is high in sub-Saharan Africa. While current prevention of mother-to-child HIV transmission (PMTCT) programs are designed to detect and treat women with chronic HIV infections, women who miss antenatal HIV testing, are in the process of seroconverting, or who acquire HIV after initial testing have infections that go undetected. Mother-to-child HIV transmission (MTCT) risk is substantially higher among women with acute infection than chronic infection. As PMTCT coverage expands and women with chronic HIV receive triple-drug antiretroviral therapy (ART), an increasing proportion of HIV infected infants will be due to undetected acute maternal HIV, making this an important frontier to address in elimination of MTCT (eMTCT) efforts. In this proposal, we aim to identify the optimal time(s) to conduct repeat maternal HIV testing for PMTCT.
The specific aims of the study are to: 1) determine the prevalence of incident or undiagnosed HIV infections among pregnant and postpartum women; 2) model the number of MTCT cases averted by conducting repeat HIV testing using a cohort decision-analytic MTCT model; 3) estimate the incremental costs and cost- effectiveness per case of infant HIV infection averted of repeat testing under different repeat testing strategies compared to no repeat testing. To conduct this study, we will test 4650 women, 930 at each time-point: 3rd trimester (if previously tested HIV negative during pregnancy); delivery; 6 weeks, 6 months, and 9 months postpartum. We will use the prevalence estimates of incident and undiagnosed maternal HIV infection from Aim 1, programmatic PMTCT data at study sites, and the scientific literature to construct and parameterize a cohort decision-analytic MTCT model and determine the number of infant HIV infections that could be averted by implementing this retesting strategy or strategies. We will build upon the MTCT model developed for Aim 2 and use costing data to evaluate cost-effectiveness for Aim 3. Pilot data generated from this study will be used to develop a future, large-scale implementation science study of optimal HIV repeat testing strategy/strategies for PMTCT and can also be leveraged for future HIV prevention studies (i.e., impact on heterosexual transmission, PMTCT in future pregnancies, and maternal HIV disease progression).
Although repeat HIV testing during pregnancy and/or the postpartum period can identify new maternal infections, link women to early HIV care and treatment, and reduce risk of infant HIV infection, it is rarely implemented in maternal and child health clinics. A repeat testing strategy or strategies capable of detecting undiagnosed maternal infection, while simultaneously minimizing infant HIV risk, is urgently needed. The proposed study will identify the time-point(s) to conduct repeat maternal HIV testing in prevention of mother-to- child HIV transmission (PMTCT) programs that avert the most infant HIV infections and determine the cost- effectiveness of implementing repeat testing.
