# Human pluripotent stem cell-based assessment of dolutegravir teratogenicity

> **NIH NIH R03** · UNIVERSITY OF HAWAII AT MANOA · 2020 · $77,771

## Abstract

Proposal Abstract
 In 2018, the Food and Drug Administration issued a warning about pregnancy risk of dolutegravir, an
antiretroviral medication to treat human immunodeficiency virus (HIV). This warning was based on an NIH-
funded observational study in Botswana, which found a significantly higher incidence of severe neural tube
defects in babies born to women who received dolutegravir before pregnancy or early in the first trimester.
Nevertheless, the World Health Organization (WHO) announced in 2019 that it still recommends dolutegravir
as preferred HIV treatment for all populations, including women of reproductive age. WHO's decision is based
on additional observational studies, suggesting that in spite of statistically higher incidence, the overall
teratogenic risk of dolutegravir is relatively small and is outweighed by the benefit as an effective anti-HIV
medication. However, it is currently unclear what mechanisms are involved in the action of dolutegravir to
induce neural tube defects and what circumstances may exacerbate the teratogenic effects of dolutegravir.
Such mechanistic understanding is essential for further studies to anticipate what types of patients are at risk
from adverse impact of dolutegravir. The goal of the proposed project is to investigate the teratogenic potential
of dolutegravir, using the novel assay platform of human embryonic stem cells that my lab established.
Specifically, we will (1) characterize molecular impact of dolutegravir in human pluripotent stem cell
aggregates, (2) determine whether dolutegravir causes teratogenic effects through folic acid antagonism, and
(3) investigate synergistic effects between dolutegravir and other anti-HIV medications. Mechanistic insights
obtained from the proposed experiments should help further investigations and endeavors to minimize
potential teratogenic risks from dolutegravir exposures.

## Key facts

- **NIH application ID:** 10043778
- **Project number:** 1R03HD102502-01
- **Recipient organization:** UNIVERSITY OF HAWAII AT MANOA
- **Principal Investigator:** YUSUKE MARIKAWA
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $77,771
- **Award type:** 1
- **Project period:** 2020-08-10 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10043778

## Citation

> US National Institutes of Health, RePORTER application 10043778, Human pluripotent stem cell-based assessment of dolutegravir teratogenicity (1R03HD102502-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10043778. Licensed CC0.

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