NIH Opportunity: Effect of HIV and Substance Use Comorbidity on the Placenta and Maternal Outcomes

Funding Opportunity Number: RFA-DA-25-021

Letter of Intent: October 15, 2024
Submission: November 15, 2024


Human immunodeficiency virus (HIV) infection is widely prevalent in individuals in the reproductive age group. With the advent of antiretroviral therapy (ART), significant progress has been made in the prevention of vertical transmission of HIV. Although ART has significant benefits in preventing vertical transmission, ART regimens are associated with higher rates of preterm birth, stillbirth, and early infant death. Optimal development and functioning of the placenta are key factors in the maintenance of pregnancy and positively correlate with maternal and fetal/neonatal outcomes. Despite this, there is a paucity of data on the impact of HIV/ART exposure on the placenta. Even less is known on the impact of HIV/ART exposure on the placenta in pregnant individuals with substance use/misuse.

In people living with HIV (PLWH) there are several pathophysiological changes in the placenta. For instance, placentae from ART-nai ve PLWH are significantly smaller compared to pregnant individuals with no HIV, suggesting a virus-mediated mechanism underlying impaired placental development. Low placental weight is associated with an increased risk of vertical transmission of HIV. In addition, women on highly active ART are more likely to have smaller placentae compared to ART-nai ve PLWH, further implying a significant impact of ART on the placenta. While these studies are targeted at delineating pathological changes in the placenta in PLWH with/without ART, the mechanisms that underlie these changes remain poorly understood. Further, little is known about placental pathologies in pregnant individuals with comorbid HIV and substance use/misuse and the impact of placental abnormalities on maternal outcomes.

Research Objective

The National Institute on Drug Abuse (NIDA) seeks to stimulate research targeted at investigating the effects of HIV and/or ART on the growth, development and functioning of the placenta in pregnant individuals with substance use/misuse, the impact of placental abnormalities on maternal outcomes in PLWH with substance use/misuse and the underlying mechanisms.

Research areas and questions of programmatic interest include, but are not limited to:

  • Assessing placental pathophysiology in pregnant individuals with addictive substance use/misuse with HIV with/without ART.
  • Elucidating the pathophysiological, pharmacological or other biological mechanisms underlying the effects of comorbid substance use/misuse and HIV/ART on the placenta.
  • Leverage existing placental repositories to determine the impact of placental abnormalities on maternal outcomes in individuals with a history of comorbid HIV and substance use/misuse.
  • Identifying the maternal outcomes of comorbid substance use and HIV which may be attributed to placental development.
  • Understanding the relationship between comorbid substance use, HIV, and abnormal placental function on adverse maternal effects.

Priority will be given to applications that propose research with the following features:

  • Transdisciplinary research teams to foster the sharing of conceptual and/or technical expertise.
  • The proposed research includes methods that examine causality across the variables of interest.

For more information, please see the opportunity website.