ABSTRACT
This K01 research and training grant aims to use innovative value of information (VOI) analysis methods to
efficiently inform the prioritization and design of potential clinical research studies related to managing virologic
failure on dolutegravir (DTG)-based ART for adults (15 years and older) in Kenya, which will also have broader
implications for resource-limited settings (RLS). The introduction of generic DTG to RLS raises new questions
about optimum clinical management for people living with HIV for whom DTG-based regimens are failing.
Conducting further clinical research can inform and improve HIV treatment guidelines; however, research funding
resources are limited. Thus, it is important that methods for setting funding priorities maximize the potential
downstream health benefits of research. The proposed K01 will leverage an individual-based HIV epidemiologic
stochastic model, developed by Dr. Duarte, for a Kenyan adult (15 years and older) population. This project’s
research aims (R1-3) are to: R1) Given currently available data, evaluate the potential cost-effectiveness of drug
resistance testing to inform choice of second-line ART for patients with unsuppressed viral load on DTG-based
ART; R2) Calculate the maximum potential returns on investment to be expected from further research related
to managing virologic failure on DTG-based ART and identify which research studies have the greatest potential
health benefit; and R3) Calculate the optimal sample size for potential key clinical studies identified in Aim 2.
The research aims of this study will provide Dr. Duarte the opportunity to pursue his training aims (T1-4),
including: T1) Develop expertise in Bayesian theory and methods for model parameterization and calibration,
conducting VOI analyses, and designing clinical studies; T2) Develop expertise in VOI analysis, including
statistical methods for meta-model development; T3) Develop expertise in using open-source decision analysis
methods, including data visualization tools; and T4) Understand the methodologic and pragmatic aspects of
clinical study design, and develop relationships with stakeholders in Kenya and other RLS, in order to build
research collaborations. These research and training goals will provide Dr. Duarte with valuable expertise that
is applicable to a wide range of important health policy issues relevant to HIV, as well as other infectious disease
challenges, thereby preparing him to transition to independence. He will plan to submit an R01 grant focused on
informing the prioritization and design of clinical research to improve pediatric and maternal HIV health outcomes
in RLS. This R01 will leverage the expertise Dr. Duarte gains through the proposed K01 and combine it with his
ongoing, pilot grant-funded work building simulation models for pediatric and maternal HIV-affected populations.
Dr. Duarte will complete his K01 career development training at the University of Minnesota, which provides an
outstanding environment for training in decision analysis and computational methods.
