Hydrocortisone may improve attention and verbal learning in women with HIV

Clinical takeaway: This proof-of-concept study suggests that low-dose hydrocortisone may improve attention, verbal learning, and memory in women with well-controlled HIV by targeting stress-response pathways.

Cognitive difficulties can persist in people with HIV despite effective antiretroviral therapy and viral suppression. In women, chronic stress and psychiatric symptoms may compound these problems, raising interest in whether the body's stress-response system could offer a new therapeutic target.

A randomized trial of 81 women with well-controlled HIV and cognitive impairment found that a low 10 mg dose of hydrocortisone produced modest improvements in selected cognitive domains. Participants also had elevated stress, a mood or anxiety disorder, or both.

In the crossover portion of the trial, hydrocortisone improved attention compared with placebo at both 30 minutes and four hours after a single dose. Verbal learning also improved at four hours, while the improvement in delayed recall did not reach statistical significance. No benefit was seen for working memory, visuospatial ability, or executive function.

The longer-term findings were less definitive. After four weeks of daily hydrocortisone, delayed recall improved within the treatment group, but the difference in change over time between hydrocortisone and placebo was not statistically significant. The investigators therefore characterized the treatment primarily as a proof-of-concept strategy rather than a proposed long-term corticosteroid therapy.

The four-week regimen was generally well tolerated, with no clinically meaningful differences in metabolic, cardiovascular, hepatic, kidney, or HIV-related safety measures. Researchers also examined cortisol, inflammation, glucocorticoid receptor function, and HIV reservoir markers, but none explained the cognitive changes.

The small trial did not reach its planned enrollment, making larger studies important before the clinical relevance or durability of the findings can be established. Still, the results point toward stress-system biology as a potentially modifiable contributor to cognitive impairment in women with HIV.

“These findings support continued investigation of stress-system modulation in larger, adequately powered trials,” the authors concluded.

Source: Rubin LH, et al. (2026 Aug 17) JAMA Netw Open. Low-dose hydrocortisone and cognition in women with HIV: a randomized clinical trial