# Effects of Glucocorticoids on Cognitive Functioning in HIV-infected Women

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2021 · $472,847

## Abstract

PROJECT SUMMARY/ABSTRACT
Despite the availability of effective antiretroviral therapies, cognitive deficits remain prevalent in HIV-infected
(HIV+) individuals. HIV+ women show prominent deficits in verbal learning and memory, and stress is a major
contributor to these deficits. In fact, we have shown that stress has more profound effects on verbal memory in
HIV+ women than in HIV-uninfected (HIV-) women. Our structural and functional neuroimaging findings link
these stress-related memory impairments in HIV+ women to prefrontal cortical atrophy and decreased prefrontal
cortex (PFC) functioning. Cortisol, a glucocorticoid that is released following a stressor and which is elevated
with chronic stress, is known to influence both hippocampal and PFC function. Clinically, this is relevant because
LDH can be administered exogenously and safely in the form of low-dose hydrocortisone (LDH). In healthy
individuals, LDH impairs cognition, but in individuals with post-traumatic stress disorder (PTSD) LDH enhances
cognition. We recently extended this line of LDH research to HIV in a pilot study of a single dose of LDH (10mg)
in HIV+ women with high levels of perceived stress but no current psychiatric comorbidities. Notably, verbal
learning and memory improved 4 hours following treatment with LDH compared to placebo. Although the
mechanisms contributing to this effect are unknown, LDH normalizes stress-induced alterations in the
hypothalamic-pituitary-adrenal (HPA) axis and inflammation. Here we propose to examine the robustness and
clinical significance of these findings in a larger sample of HIV+ women demonstrating cognitive dysfunction and
reporting high levels of stress, trauma history, and mental health risk factors. Women meeting enrollment criteria
will complete three cognitive assessments. The first and second assessments will be embedded in a double-
blind, placebo-controlled, cross-over study of a single administration of LDH (10 mg in pill form) versus placebo
(targeted n=100). The within-subject design controls for common cofounds (e.g., psychological risk factors,
substance use history) that could complicate interpretation of LDH effects in a population of HIV+ women. We
will measure cognitive performance 30 minutes and 4 hours post-dosing, because an emerging literature shows
that the cognitive effects of LDH depends on timing of the assessment post-dosing. The 30-minute assessment
addresses how the maximal cortisol levels following LDH affect cognition. This immediate assessment is
standard in studies of stress and cognition and allows for comparisons with the broader literature. More novel
and clinically important is the 4-hour assessment which occurs post-peak, when cortisol levels are more steady
state and typical of the broader daily cortisol profile following LDH. The third assessment will take place after 4
weeks of treatment with LDH or placebo. That assessment addresses the clinical significance and safety of
longer-term LDH treatmen...

## Key facts

- **NIH application ID:** 10219073
- **Project number:** 5R01MH113512-05
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Leah Helane Rubin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $472,847
- **Award type:** 5
- **Project period:** 2017-09-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10219073

## Citation

> US National Institutes of Health, RePORTER application 10219073, Effects of Glucocorticoids on Cognitive Functioning in HIV-infected Women (5R01MH113512-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10219073. Licensed CC0.

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