Low-dose hydrocortisone may improve memory in women with human immunodeficiency virus infection
1. Low-dose hydrocortisone (LDH) is well tolerated and improves verbal learning and memory, working memory, and attention in adult women with human immunodeficiency virus (HIV) infection.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Women with HIV demonstrate deficits in verbal learning, memory, cognition, and increased susceptibility to stress-related cognitive impairment. The hypothalamic-pituitary-adrenal (HPA) axis has been shown to link chronic stress, psychiatric symptoms, and cognitive impairment through the effects of glucocorticoids on learning, memory, attention, and executive function. While high-dose corticosteroids impair cognition in healthy individuals, LDH has been shown to modulate the HPA axis and improve performance across cognitive domains.
This study was a two-phase, placebo-controlled randomized controlled trial conducted in the United States from November 2017 to July 2023. Participants included women aged 18 to 65 years with confirmed HIV infection, stable antiretroviral therapy (ART), plasma HIV RNA levels of less than 1000 copies/mL, and elevated stress, mood or anxiety disorders, and cognitive impairment in 1 of 7 domains (Women’s Interagency HIV Study (WIHS) neuropsychological test battery). Patients were randomized to 4 different groups. In phase 1, patients in group A received a single LDH 10 mg dose with immediate (30 minutes) cognitive evaluation followed by a 30-day washout period and repeat immediate cognitive evaluation after a single placebo dose, patients in group B received a single placebo dose with immediate cognitive evaluation followed by a 30-day washout period and repeat immediate cognitive evaluation after a single LDH 10 mg dose, patients in group C received a single LDH 10 mg dose with delayed (4 hours) cognitive evaluation followed by a 30-day washout period and repeat delayed cognitive evaluation after a single placebo dose, patients in group D received a single placebo dose with delayed cognitive evaluation followed by a 30-day washout period and repeat delayed cognitive evaluation after a single LDH 10 mg dose. In phase 2, patients in groups A and B received daily placebo, and patients in groups C and D received daily LDH. The primary outcomes were verbal learning and memory (assessed with the Hopkins Verbal Learning Test–Revised [HVLT-R]), working memory (assessed with the Letter-Number Sequencing [LNS] task), and visuospatial abilities (assessed with the Repeatable Battery for the Assessment of Neuropsychological Status [RBANS] Line Orientation subtest).
Overall, this study found LDH produced acute improvements in verbal learning and attention, and short-term improvements in memory. LDH was well tolerated.
Click here to read this study in JAMA Network Open
Relevant reading: A single low dose of hydrocortisone enhances cognitive functioning in HIV-infected women
In-Depth [randomized clinical trial]:
Women with HIV experience higher rates of risk factors for cognitive impairment, including trauma, chronic stress, and depression. The HPA axis has been implicated in the physiological connection between cognitive impairment and these risk factors. It is unclear if LDH can modulate the HPA axis to decrease cognitive impairment in these patients. This two-phase study assessed the impact of LDH on various cognitive domains in adult women with HIV infection.
This trial included 81 patients who were randomized to groups A (n = 20; mean [SD] age, 53.2 [10.1] years), B (n = 22; mean [SD] age, 54.7 [8.5] years), C (n = 20; mean [SD] age, 56.4 [6.1] years), and D (n = 19; mean [SD] age, 56.6 [6.9] years). Compared to placebo, LDH produced a cortisol increase peaking 75 minutes post-dose (Cohen d = 1.30; 95% CI, 1.00 to 1.60; P < .001). At 4 hours post dose, LDH significantly improved verbal learning and memory compared with placebo (Cohen d = 0.35; 95% CI, 0.02 to 0.69; P = .03). LDH improved attention at 30-minutes (Cohen d = 0.38; 95% CI, 0.04 to 0.71; P = .02) and 4-hours (Cohen d = 0.42; 95% CI, 0.08 to 0.76; P = .01). LDH had no significant effect on working memory of visuospatial abilities at either 30-minutes or 4-hours. In phase 2, daily LDH significantly improved working memory compared to placebo (Cohen d = 0.71; 95% CI, 0.22 to 1.20; P = .005). Daily LDH did not significantly change verbal learning and memory or visuospatial abilities compared to placebo. The authors report LDH was well tolerated. However, they do not report quantitative measurements of side effects.
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