Ghura, Gross, Jordan-Sciutto, Dubroff, Schnoll, Collman, Ashare (2019) Bidirectional Associations among Nicotine and Tobacco Smoke, NeuroHIV, and Antiretroviral Therapy Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology ()
People living with HIV (PLWH) in the antiretroviral therapy (ART) era may lose more life-years to tobacco use than to HIV. Yet, smoking rates are more than twice as high among PLWH than the general population, contributing not just to mortality but to other adverse health outcomes, including neurocognitive deficits (neuroHIV). There is growing evidence that synergy with chronic inflammation and immune dysregulation that persists despite ART may be one mechanism by which tobacco smoking contributes to neuroHIV. This review will summarize the differential effects of nicotine vs tobacco smoking on inflammation in addition to the effects of tobacco smoke components on HIV disease progression. We will also discuss biomarkers of inflammation via neuroimaging as well as biomarkers of nicotine dependence (e.g., nicotine metabolite ratio). Tobacco smoking and nicotine may impact ART drug metabolism and conversely, certain ARTs may impact nicotine metabolism. Thus, we will review these bidirectional relationships and how they may contribute to neuroHIV and other adverse outcomes. We will also discuss the effects of tobacco use on the interaction between peripheral organs (lungs, heart, kidney) and subsequent CNS function in the context of HIV. Lastly, given the dramatic rise in the use of electronic nicotine delivery systems, we will discuss the implications of vaping on these processes. Despite the growing recognition of the importance of addressing tobacco use among PLWH, more research is necessary at both the preclinical and clinical level to disentangle the potentially synergistic effects of tobacco use, nicotine, HIV, cognition and immune dysregulation, as well as identify optimal approaches to reduce tobacco use. Graphical Abstract Proposed model of the relationships among HIV, ART, smoking, inflammation, and neurocognition. Solid lines represent relationships supported by evidence. Dashed lines represent relationships for which there is not enough evidence to make a conclusion. (a) HIV infection produces elevated levels of inflammation even among virally suppressed individuals. (b) HIV is associated with deficits in cognition function. (c) Smoking rates are higher among PLWH, compared to the general population. (d) The nicotine metabolite ratio (NMR) is associated with smoking behavior. (e) HIV and tobacco use are both associated with higher rates of psychiatric comorbidities, such as depression, and elevated levels of chronic stress. These factors may represent other mechanisms linking HIV and tobacco use. (f) The relationship between nicotine, tobacco smoking, and inflammation is complex, but it is well-established that smoking induces inflammation; the evidence for nicotine as anti-inflammatory is supported in some studies, but not others. (g) The relationship between tobacco use and neurocognition may differ for the effects of nicotine (acute nicotine use may have beneficial effects) vs. tobacco smoking (chronic use may impair cognition). (h) Elevated levels of inflammation may be associated with deficits in cognition. (i) PLWH may metabolize nicotine faster than those without HIV; the mechanism is not yet known and the finding needs validation in larger samples. We also hypothesize that if HIV-infection increases nicotine metabolism, then we should observe an attenuation effect once ART is initiated. (j) It is possible that the increase in NMR is due to ART effects on CYP2A6. (k) We hypothesize that faster nicotine metabolism may result in higher levels of inflammation since nicotine has anti-inflammatory properties.