The prevalence of smoking is increased in the HIV-infected population. Active smoking is independently associated with higher risk of cardiovascular disease and other co-morbidities including malignancies and osteoporosis in HIV. However, the independent contribution of smoking to the heightened inflammation, immune activation, and cardiovascular risk remains unclear. We recently showed that smoking status is independently associated with increased levels of several inflammatory markers, and that higher inflammatory markers are associated with cardiovascular risk, diabetes and AIDS or non-AIDS clinical events in subjects receiving antiretroviral therapy. This application gathers a superb group of experts in HIV disease, vascular inflammation, immunology, vascular imaging, behavioral interventions, and oral microbiome studies to determine whether smoking status and furthermore smoking cessation, affect cardiovascular disease risk in HIV and the mediation effect of heightened inflammation, immune activation, oxidative stress and oral microbiome changes. Understanding the specific contribution of smoking to the heightened inflammation and immune activation in HIV-infected subjects on antiretroviral therapy has the potential to have a significant impact on prevention of HIV co-morbidities including cardiovascular disease.

Public Health Relevance

Mortality in people living with HIV has significantly decreased, however several complications of HIV and its therapy have emerged, including increased risk of heart disease, diabetes, and malignancies. These complications have been linked to high inflammation and immune activation. Smoking is very common in HIV and has been linked to higher risk of heart disease and malignancies in the general population and in people living with HIV. This study will examine the relationship between smoking and cardiovascular and metabolic complications and the interplay of inflammation, immune activation, oxidative stress, and the changes in oral bacteria and fungi on these complications and the smoking effect.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
High Priority, Short Term Project Award (R56)
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Special Emphasis Panel (ZHL1-CSR-B (S1))
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Iturriaga, Erin
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Case Western Reserve University
Schools of Medicine
United States
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Mukherjee, Pranab K; Chandra, Jyotsna; Retuerto, Mauricio et al. (2018) Dysbiosis in the oral bacterial and fungal microbiome of HIV-infected subjects is associated with clinical and immunologic variables of HIV infection. PLoS One 13:e0200285
Dirajlal-Fargo, Sahera; Sattar, Abdus; Kulkarni, Manjusha et al. (2017) Soluble TWEAK may predict carotid atherosclerosis in treated HIV infection. HIV Clin Trials 18:156-163
Park, Michelle S; Hileman, Corrilynn O; Sattar, Abdus et al. (2017) Incidental findings on chest computed tomography are common and linked to inflammation in HIV-infected adults. Antivir Ther 22:127-133