A TWO-PHASE randomised medical trial has proven that low-dose hydrocortisone acutely sharpens verbal studying, reminiscence and a focus in virally suppressed ladies with HIV, pointing to stress-system modulation as a path to treating cognitive impairment in HIV.
Cognitive Impairment in HIV
Ladies with HIV expertise excessive charges of trauma, power stress, and melancholy, all of that are linked to cognitive impairment. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, glucocorticoid receptor operate, irritation and HIV persistence have develop into main candidate mechanisms, but no intervention has instantly focused these pathways.
Single-Dose Crossover and 4-Week Therapy Phases
The placebo-controlled trial ran at Johns Hopkins College between November 2017 and July 2023. Eighty-one virally suppressed ladies with HIV aged 18 to 65 years, imply age 55.2 years (SD 8.0), have been randomised to one in all 4 remedy sequences. All had elevated self-reported stress, a temper or anxiousness dysfunction, or each, alongside goal impairment in a minimum of one cognitive area.
Part 1 was a double-blind crossover comparability of a single 10 mg oral dose of low-dose hydrocortisone (LDH) with placebo at half-hour and 4 hours.
Part 2 in contrast each day 10 mg LDH with placebo over 4 weeks. Main outcomes have been verbal studying and reminiscence (Hopkins Verbal Studying Check-Revised), working reminiscence (Letter-Quantity Sequencing) and visuospatial capacity.
Secondary outcomes coated consideration, govt operate, security and mechanistic markers together with salivary cortisol, inflammatory biomarkers, and HIV reservoirs.
Enhancements in Consideration and Studying
The outcomes revealed that LDH raised cortisol, peaking 75 minutes submit dose (p < 0.001). At 4 hours it improved studying versus placebo (p = 0.03), whereas verbal delayed recall fell in need of significance (p = 0.05). Consideration improved at half-hour (p = 0.02) and 4 hours (p = 0.01). Working reminiscence and visuospatial capacity have been unchanged.
In part 2, reminiscence improved with each day LDH however not placebo (p = 0.005), though the remedy by time interplay was not important (p = 0.22). No biomarker tracked cognitive change.
Reminiscence and studying impairment have been frequent at baseline, affecting 58 (71.6%) and 41 (50.6%) contributors, which helps the practical relevance of the domains that responded. LDH was properly tolerated, and impact sizes sit within the vary reported for different cognitive interventions.
As a result of peripheral biomarkers didn’t clarify the profit, the mechanism behind cognitive impairment in HIV stays open, and the authors place LDH as a proof-of-concept intervention reasonably than long-term corticosteroid remedy.
Reference
Rubin LH et al. Low-dose hydrocortisone and cognition in ladies with HIV: a randomized medical trial. JAMA Netw Open. 2026;9(8):e2629185
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