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To evaluate the effects of cannabis and/or cocaine use on inflammatory, oxidative stress status and circulating monocyte subsets in HIV-infected individuals under antiretroviral therapy.Soluble CD14 (sCD14), intestinal fatty acid-binding protein (IFABP), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-8, IL-10, C-reactive protein (CRP) and oxidative stress markers were examined. The monocyte subsets and their activation and cytokine production by peripheral blood mononuclear cells (PBMCs) of HIV-1 infected individuals upon lipopolysaccharide (LPS)-stimulation were also investigated.sCD14, IFABP, TNF-α, IL-6, IL-8 and IL-10 levels were evaluated using ELISA, CRP by turbidimetry; lipid peroxidation (TBARS) spectrofluometrically and total thiol levels by using 5–5′-dithio-bis (2-nitrobenzoic acid) reagent. Monocyte subsets and activation were assessed by flow cytometry.All HIV-infected drug user groups showed higher sCD14 levels compared to HIV+ non-drug users. IFABP was increased in HIV+ drug-users in relation to healthy individuals. Cannabis use lowered the percentages of inflammatory, non-classical, activated-classic, and activated-inflammatory monocytes. Cocaine users showed increased plasmatic TNF-α and TBARS levels, decreased thiols content and lower activated-classic and inflammatory-monocyte percentages. Cannabis-plus-cocaine use increased CRP, IL-8 and IL-6/IL-10 ratio, but decreased thiols content, and inflammatory and activated-classic monocyte percentages. PBMCs of cannabis and cannabis-plus-cocaine users showed low potential cytokine production either spontaneously or under LPS-stimulation.In HIV infection the use of cannabis induces predominantly an anti-inflammatory profile. The use of cocaine and cannabis-plus-cocaine showed a mixed pro- and anti-inflammatory profile, with predominance of inflammatory status. Further studies are required to better understand the action of these drugs in HIV infection.