Stimulant use is associated with immune activation and depleted tryptophan among HIV-positive persons on anti-retroviral therapy

Abstract

Cocaine, crack, and methamphetamine are stimulants that promote autonomic nervous system activation. Although these stimulants may have immunomodulatory effects, relatively few studies have examined this possibility. The present cross-sectional investigation utilized baseline data from 127 HIV-positive individuals on anti-retroviral therapy (ART) that were enrolled in a randomized controlled trial. The goal of this study was to examine whether stimulant use is independently associated with immune activation and indices of tryptophan degradation. Forty-four participants reported using stimulants 2-3 times a month or more (i.e., monthly stimulant use) and a sub-set of these (n=27) reported using stimulants once a week or more (i.e., weekly stimulant use) during the past three months. These stimulant-using groups were compared to a group of participants who reported no stimulant use (n=83) during the past three months. Results indicated that individuals who reported either monthly or weekly stimulant use displayed elevated neopterin, a measure of immune activation. Those who reported weekly stimulant use also displayed a markedly elevated HIV viral load and lower tryptophan levels. Even after controlling for self-reported ART non-adherence, weekly stimulant use was independently associated with higher neopterin, elevated HIV viral load, and lower tryptophan. To our knowledge, this is the first study to observe that stimulant use may independently promote immune activation and tryptophan degradation among HIV-positive persons on ART. Further research is needed to replicate these findings and examine the plausible bio-behavioral pathways that may account for the effects of stimulant use on HIV disease markers and depleted tryptophan.

Figure 1. Mean Differences in the Kynurenine/Tryptophan Ratio as a Function of Depressive Symptom Severity Category

After controlling for time since HIV diagnosis, individuals with moderate-severe depression had a significantly higher kynurenine/tryptophan ratio (Mean = 58.76, SE = 4.07) compared to either: a) those with no depression (Mean = 47.97, SE = 3.32; p < .05) or b) those mild-moderate depression (Mean = 45.97, SE = 3.71; p < .05).