Scholars@Duke publication: Longitudinal associations between depression, substance use, and immune activation and inflammation: A secondary analysis of men who have sex with men living with HIV in Brazil (HPTN 063).

Longitudinal associations between depression, substance use, and immune activation and inflammation: A secondary analysis of men who have sex with men living with HIV in Brazil (HPTN 063).

Publication , Journal Article

Cherenack, EM; Larson, ME; Roach, ME; Feaster, DJ; Friedman, RK; Safren, SA; Carrico, AW

Published in: Brain Behav Immun

January 21, 2026

BACKGROUND: Limited research has examined the longitudinal interplay of depression, substance use, and immune dysregulation among men with HIV. METHODS: We analyzed longitudinal data from 100 men who have sex with men (MSM) living with HIV enrolled in the HPTN 063 cohort (2011-2013) in Brazil. Depressive symptom severity, alcohol use severity, and recent illicit stimulant use were assessed quarterly over 12 months. Soluble markers of immune activation (sCD14) and inflammation (IL-6) were measured at baseline and at a 12-month visit. RESULTS: Depressive symptom severity and alcohol use severity showed substantial within-person variability across time, whereas stimulant use remained relatively stable. These psychosocial factors were weakly intercorrelated. Controlling for baseline IL-6, the odds of having detectable IL-6 at 12 months increased by 2 % for each point increase in the proportion of visits with elevated depression, 7 % for each point increase in mean depressive severity across visits, 5 % for each point increase in depressive severity at nine months, and 6 % for each point increase in depressive severity at 12 months. Effects persisted after controlling for baseline HIV viral load. Controlling for baseline sCD14, estimated 12-month sCD14 increased 8 ng/mL for each point increase in 12-month depressive severity and 20 ng/mL for each point increase in 12-month alcohol use severity. The alcohol-sCD14 association was attenuated when adjusting for HIV viral load. Neither baseline IL-6 nor sCD14 strongly predicted future depressive symptoms or substance use. CONCLUSIONS: Depressive symptoms predicted future inflammation and current immune activation. Research should examine if interventions to treat depression can improve immune functioning.