Perceived stress and norepinephrine predict the effectiveness of response to protease inhibitors in HIV

In vitro evidence has suggested that increasing levels of norepinephrine (NE) can accelerate HIV replication; however, the importance in a clinical setting has not been tested.

The purpose of this study was to determine if perceived stress as well as the stress hormones NE and cortisol would predict the response to starting a new protease inhibitor (PI) prospectively.

Perceived stress, urinary cortisol and norepinephrine, CD4 and viral load (VL) were measured in people with HIV before starting a new PI and six months later (an average of three months after starting the new PI) in order to determine CD4 and VL response to the PI.

Higher perceived stress significantly predicted lower effectiveness of the new PI in increasing CD4 and decreasing VL controlling for age, duration of new PI, baseline CD4/VL, sexually transmitted diseases (STDs), and gender/ethnic risk groups. Higher norepinephrine, but not cortisol, predicted worse VL response to PIs and, in fact, mediated the relationship between perceived stress and change in VL.

Perceived stress and high norepinephrine levels are prospectively associated with a poorer response to starting a new PI. Assessing stress and norepinephrine levels in patients starting on antiretroviral medications might be clinically useful.