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Updated: Dec 28, 2025

Author Spotlight: Exploring the Role of Unfolded Protein Response in HIV-1 Replication and Infectivity
Published on: June 14, 2024
HIV-1 Infection, Injecting Drug Use, and Neuroendocrine Response to Psychological Stress
Raymond L Ownby1, Drenna Waldrop-Valverde2, Adarsh M Kumar3
1Department of Psychiatry and Behavioral Medicine, Nova Southeastern University, Fort Lauderdale FL, USA.
Background:
Previous studies have suggested that HIV-1 infection is associated with neuroendocrine abnormalities including alterations in autonomic nervous system (ANS) activity. The norepinephrine (NE) response to cold pressor stress, an α-adrenergic challenge, is blunted in HIV-1 infection. Given the relation of ANS activity to the function of the hypothalamic-pituitary-adrenal (HPA) axis and its role in cognitive functioning, changes in response to stress may be a factor in HIV-related cognitive dysfunction.
Objective:
In this study, we evaluated the NE and cortisol response of persons in three groups.
Design/Participants:
We studied stress response in three groups: (1) those with HIV-1 infection and a history of injecting drug use (IDU), those with HIV-1 infection but no IDU, and a control group of uninfected individuals without a history of IDU. Stress was induced by administering a neuropsychological test known to induce an immediate increase in NE, the Stroop Color-Word Test. Blood samples were obtained immediately before and after participants completed the Stroop and then at two intervals over the next 20 minutes. Data were analyzed using mixed-effects repeated measures models.
Main Measures:
Serum norepinephrine, epinephrine, and cortisol.
Results:
Analyses showed that those with both HIV-1 infection and history of IDU had a significantly greater NE response to stress that did not return to baseline over 20 minutes compared to those without infection or IDU history. Epinephrine and cortisol responses followed similar patterns, but between-group differences were not statistically significant.
Conclusions:
The combination of history of IDU and HIV infection may produce an exaggerated neuroendocrine response that does not quickly return to baseline levels. Given the potential impact of these on cognitive and physical function in affected these individuals, implementing stress management techniques with them may be important.
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