Abstract
Mild-to-moderate tobacco smoking is highly prevalent in HIV-infected individuals, and is known to exacerbate HIV pathogenesis. The objective of this study was to determine the specific effects of mild-to-moderate smoking on viral load, cytokine production, and oxidative stress and cytochrome P450 (CYP) pathways in HIV-infected individuals who have not yet received antiretroviral therapy (ART). Thirty-two human subjects were recruited and assigned to four different cohorts as follows: a) HIV negative non-smokers, b) HIV positive non-smokers, c) HIV negative mild-to-moderate smokers, and d) HIV positive mild-to-moderate smokers. Patients were recruited in Cameroon, Africa using strict selection criteria to exclude patients not yet eligible for ART and not receiving conventional or traditional medications. Those with active tuberculosis, hepatitis B or with a history of substance abuse were also excluded. Our results showed an increase in the viral load in the plasma of HIV positive patients who were mild-to-moderate smokers compared to individuals who did not smoke. Furthermore, although we did not observe significant changes in the levels of most pro-inflammatory cytokines, the cytokine IL-8 and MCP-1 showed a significant decrease in the plasma of HIV-infected patients and smokers compared with HIV negative non-smokers. Importantly, HIV-infected individuals and smokers showed a significant increase in oxidative stress compared with HIV negative non-smoker subjects in both plasma and monocytes. To examine the possible pathways involved in increased oxidative stress and viral load, we determined the mRNA levels of several antioxidant and cytochrome P450 enzymes in monocytes. The results showed that the levels of most antioxidants are unaltered, suggesting their inability to counter oxidative stress. While CYP2A6 was induced in smokers, CYP3A4 was induced in HIV and HIV positive smokers compared with HIV negative non-smokers. Overall, the findings suggest a possible association of oxidative stress and perhaps CYP pathway with smoking-mediated increased viral load in HIV positive individuals.
Highlights
The prevalence of mild-to-moderate tobacco smoking is approximately 3-fold higher in HIV-infected individuals (~60%) than in the general population (~ 20%) [1]
Liver damage and lung disease since these alter the metabolism of tobacco constituents such as nicotine; 3) Individuals with other infectious diseases, such as documented malaria, tuberculosis, and hepatitis B since hepatitis and active TB are prevalent in HIV-infected population, and some of these diseases are known to interact with HIV [28]; 4) Individuals who were receiving antiretroviral therapy (ART)
Our analysis showed that the subject-to-subject variation in CD4 counts, viral load, cytokine production, and oxidative stress was not significant on the basis of age and gender differences
Summary
The prevalence of mild-to-moderate tobacco smoking is approximately 3-fold higher in HIV-infected individuals (~60%) than in the general population (~ 20%) [1]. Smoking/ nicotine has shown to enhance HIV-1 replication, especially in alveolar macrophages and microglia [2,3]. The specific effects of mild-to-moderate smoking on the components of HIV pathogenesis such as inflammatory cytokines and oxidative stress, is poorly studied. Cytokines have shown to play an important role in development of viral latency and maintenance of latently infected CD4+ T cells during antiretroviral therapy (ART) [8]. Oxidative stress is known to play a significant role in HIV-1 pathogenesis [9,10,11]. Oxidative stress has been linked to HIV-1 replication in monocytes/macrophages [9,12]. A report suggested the role of iron and oxidative stress in smoking-mediated HIV replication in alveolar macrophages [13]. The pathway leading oxidative stress, especially in monocytes, in HIV-infected smokers is unknown
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