# Characterizing adherence and estimating per-protocol effects for pediatric dolutegravir use

> **NIH NIH F30** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $41,012

## Abstract

PROJECT SUMMARY
 Continued access and adherence to antiretroviral therapy (ART) is crucial for pediatric populations
living with HIV to prevent AIDS-related comorbidities. However, there are several unique challenges to
treatment adherence in pediatric populations, including caregiver factors, and medication palatability and
tolerability. Little work has been done in characterizing patterns and factors related to the timing of ART
nonadherence since initiation of therapy in children. Additionally, new ART formulations available for adults
have been slower to obtain approval for use in pediatric populations due to difficulty in assessing efficacy in
trials. Bringing modern causal inference methods to the analyses of pediatric trials through rigorous
estimation of per-protocol effects can help overcome some of these difficulties, and help bring
analyses of pediatric trials into the modern age.
 The objectives of the proposal are to (1) characterize the barriers to pediatric dolutegravir
combination therapy adherence, and (2) estimate per-protocol effects of treatment failure by 96 weeks
in the pediatric HIV trial, taking into consideration the unique barriers to medication adherence in
pediatric populations. Data from the ODYSSEY trial, a phase II/II open-label non-inferiority trial assessing
dolutegravir-based ART compared to standard of care in an international sample of children aged 2 to 18, will
be used to characterize baseline and time varying factors influencing time to protocol deviation, and then
estimate per-protocol effects impacting 96-week treatment failure correcting for such protocol deviations
through implementation of modern causal inference methods and machine learning.
 The completion of the proposed aims will provide evidence on characteristics contributing to timing of
protocol deviation and estimates of per-protocol effects of treatment failure by 96 weeks corrected for such
protocol deviations in the ODYSSEY trial for first or second line dolutegravir use compared to standard of care
in a pediatric population. These results will (1) provide substantial information on factors related to
timing of eventual ART nonadherence so that appropriate clinical intervention can be developed to
prevent nonadherence related to these factors, and (2) provide an example of modern per-protocol
analyses in pediatric trials which will serve as guidelines for future per-protocol analyses in pediatric
trials. The training plan outlined in this F30 proposal will provide the applicant with necessary skills in modern
causal inference methods and clinical medicine to become a productive and successful physician scientist at
the intersection of pediatrics and application of modern causal inference methods for pediatric trials.

## Key facts

- **NIH application ID:** 10901424
- **Project number:** 1F30HD115415-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Catherine Xin-Di Li
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $41,012
- **Award type:** 1
- **Project period:** 2024-06-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10901424

## Citation

> US National Institutes of Health, RePORTER application 10901424, Characterizing adherence and estimating per-protocol effects for pediatric dolutegravir use (1F30HD115415-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10901424. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*