Adam W Carrico, Emily M Cherenack, Margaret E Roach, Elise D Riley, Olorunleke Oni, Samantha E Dilworth, Steven Shoptaw, Peter Hunt, Sabita Roy, Suresh Pallikkuth, Savita Pahwa

Microbial translocation and monocyte activation predict mortality in treated HIV. We examined whether substance use independently contributes to these pathophysiologic processes. Cross-sectional study at baseline for a randomized controlled trial. HIV-positive, methamphetamine-using men who have sex with men (MSM) with undetectable HIV viral load (< 40 copies/mL) were enrolled. We examined if plasma biomarkers of monocyte activation and intestinal barrier integrity were associated with the following: 1) reactive urine toxicology results (Tox+) for stimulants (i.e., methamphetamine or cocaine); and 2) substance use severity measured by the Addiction Severity Index. Multiple linear regression models adjusted for age, antiretroviral therapy regimen, CD4+ T-cell count, interleukin-6, and alcohol use severity. The sample of 84 virally suppressed MSM had a median CD4+ T-cell count of 645 cells/mm. Those who were Tox+ for stimulants displayed higher soluble CD14 (sCD14) levels (2,087 versus 1,801 ng/ml; p = .009), and this difference remained significant after adjusting for covariates (standardized Beta = 0.23; p = 0.026). Greater substance use severity was also independently associated with higher sCD14 after adjusting for covariates (standardized Beta = 0.29, p = 0.013). Being Tox+ for stimulants and substance use severity were not associated with soluble CD163 (sCD163) or intestinal fatty acid binding protein (iFABP) levels (p's > 0.05). Monocyte activation is one plausible mechanism by which stimulant use may increase clinical HIV progression.