Findings from a recent study find enduring effects of LDH on learning and memory, suggesting potential clinical utility in women with HIV.
Past research has found that administration of hydrocortisone, often used to treat inflammation-related conditions, works to enhance aspects of learning and memory in certain populations, including those suffering from post-traumatic stress disorder.
HIV is a chronic condition that is known to contribute to continuing inflammation in those infected, so it makes sense that researchers have turned to hydrocortisone to see if it could be beneficial to those with the virus. Low dose hydrocortisone (LDH) proved to demonstrate only acute enhancing effects on verbal learning in HIV-positive men, but the effect LDH may have on the cognitive function of HIV-positive women have remained largely unknown.
Which is why Leah H. Rubin, PhD, MPH, MA, assistant professor of Neurology and Epidemiology at Johns Hopkins School of Medicine, along with her colleagues, set out to find some answers.
“It’s important to study ways that we can improve cognition in women living with HIV,” Dr. Rubin told Contagion® in a recent interview at the 25th Annual Conference on Retroviruses and Opportunistic Infections (CROI). “Particularly, I think, HIV-infected women may actually be more cognitively vulnerable compared to HIV-infected men.”
As past research has noted stress-related learning and memory impairment in the context of HIV, a better understanding is needed to understand what the mechanisms are that contribute to those effects, and how probing different systems may influence cognitive function in those with the virus. Dr. Rubin shared with us what led her and her team to explore this further (see video below).
The double-blind, placebo-controlled, cross-over study sought to determine what the time-dependent effects of glucocorticoids were—which could be done by giving LDH 10 mg—and how they would influence cognitive function in a total of 36 women with HIV. The women were randomized to receive either LDH or placebo, with the opposite treatment administered 1 month later.
“We would test their cognitive function 30 minutes after taking the pill when endogenous cortisol levels are high, and then again 4 hours later, when the drug is out of the system and cortisol levels are low,” Dr. Rubin told us. “What you’re doing for each individual is looking at their performance at each of those time points—when they’re on drug versus when they’re on placebo.”
Dr. Rubin and her colleagues found that compared with placebo, LDH significantly increased salivary cortisol levels; levels returned to baseline 4 hours after being administered.
“What we found was that in women living with HIV that we see cognitive improvements on aspects of learning and memory that are not just at that 30-minute timepoint when cortisol levels are high,” Dr. Rubin stressed, “but we see these delayed effects, so when the drug is out of the system, we see that these benefits remain on aspects of learning and memory.” Dr. Rubin elaborated on the implications of these findings (see video below).
LDH enhanced verbal learning and memory, working memory, behavioral inhibition, and visuospatial abilities at the 30-minute assessment, the authors write. Even at the 4-hour assessment, verbal learning and memory were enhanced in those who received LDH compared with those who just received placebo. The authors note that LDH did not appear to impact stress or anxiety or any other cognitive domain at either assessment time point.
“I just want to mention that we’ve done this in HIV-infected men and we’ve only seen benefits on aspects of learning at the 30-minute time point. We see no benefits at 4 hours,” Dr. Rubin stressed. “And so, we see sex differences. There are sex differences in inflammation; there are sex differences in the HPA access and its reactivity and vulnerability to cognition, and there are sex differences in cognitive function.”
Larger, longer-term studies are currently underway to verify potential sex-specific cognitive enhancing effects of LDH and the clinical significance of these effects in those with HIV, she added.