Like
HIV infection, smoking, which is common among HIV-infected persons, is associated with chronic, systemic
inflammation. However, the possible augmentative effects of
HIV infection and smoking and other types of tobacco usage on indices of systemic
inflammation and the impact of
combination antiretroviral therapy (cART) thereon remain largely unexplored and represent the focus of the current study. Of the total number of HIV-infected persons recruited to the study (n = 199), 100 were categorised as pre-cART and 99 as virally suppressed (HIV viral load < 40 copies/mL). According to serum
cotinine levels, 144 and 55 participants were categorised as nonusers and users of tobacco, respectively. In addition to
cytokines (IL-6, IL-8, and TNF-α) and
chemokines (IP-10, MIG, IL-8, MCP-1, and
RANTES), other
biomarkers of systemic
inflammation included
C-reactive protein (CRP), β2-microglobulin, and those of neutrophil activation [ICAM-1,
L-selectin,
matrix metalloproteinase-9 (
MMP-9)], microbial translocation (
soluble CD14,
LPS-binding protein), and oxidative stress (
cyclophilin A,
surfactant D). These were measured using multiplex bead array, ELISA, and immunonephelometric procedures. Viral suppression was associated with significant decreases in the levels of most of the
biomarkers tested (P < 0.0037-0.0008), with the exceptions of CRP,
cyclophilin A, and MMP-9. With respect to tobacco usage, irrespective of cART status, circulating levels of β2-microglobulin,
cyclophilin A, and
RANTES were significantly elevated (P < 0.042-0.012) in users vs nonusers. Additional analysis of the groups of tobacco users and nonusers according to cART status revealed high levels of
RANTES in pre-cART/tobacco users relative to the three other subgroups (P < 0.004-0.0001), while more modest increases in
cyclophilin A and MMP-9 (P < 0.019-0.027) were observed in comparison with the cART/tobacco user subgroup. Notwithstanding the efficacy of cART in attenuating HIV-associated, chronic systemic
inflammation, the current study has identified
RANTES as being significantly and seemingly selectively increased in those with active
HIV infection who use tobacco, a mechanism which may underpin augmentative proinflammatory activity.