In this study, we sought to compare the mortality associated with smoking in HIV-positive and HIV-negative veterans and to examine how smoking status versus pack-years of smoking influenced outcomes. We found that current smoking at study enrollment was significantly associated with mortality when considering all patients. When stratified by HIV status, smoking status and pack-years were significantly associated with mortality among those with HIV. After adjusting for predictors known to be associated with mortality and potential confounders, current smoking and pack-years remained significantly associated with increased mortality among HIV-positive subjects. Additionally, we found that smoking was associated with increased comorbid diseases and respiratory symptoms, and with decreased quality of life. These associations were consistent when examined according to pack-years as well as smoking status, with greatest prevalence of comorbid diseases encountered in the heaviest smokers (≥20 pack-years).
Although current smoking was associated with mortality in our cohort, the increase in mortality that we observed in the subgroup of HIV-negative current smokers was not statistically significant, most likely owing to decreased statistical power in this group for such stratified analyses. The HIV-negative group had a smaller sample size and fewer deaths during the average of 5.2 years of follow-up, with only 72 of the 272 deaths occurring in the HIV-negative veterans. The Kaplan-Meier survival curves in are nonetheless suggestive of a trend towards greater mortality among HIV-negative current smokers when compared with other groups.
Of note, we found that mortality rates were substantially increased in White veterans compared with Black veterans. Previous studies have also demonstrated increased mortality among hospitalized white veterans compared with black veterans (Deswal, Petersen, Souchek, Ashton, & Wray, 2004
; Jha, Shlipak, Hosmer, Frances, & Browner, 2001
) Reasons for these differences are not clear from our analyses, and further studies are needed to clarify these findings.
Our results demonstrate the significant negative consequences of cigarette smoking on outcomes for HIV-positive patients. The greatest estimates for increased mortality were associated with current smoking rather than reported pack-years among HIV-positive subjects. These findings suggest that any amount of smoking may be hazardous to HIV-positive patients, and that smoking cessation should be prioritized for patients regardless of their pack-year history.
Improved smoking cessation among HIV-positive patients is needed. Although the number of studies are limited, data suggest that smoking cessation interventions may be effectively applied in HIV-positive populations (Cummins, Trotter, Moussa, & Turham 2005
; Vidrine, Arduino, Lazev, & Gritz 2006
; Wewers, Neidig, & Kihm 2000
). One study combining nicotine patch and counseling found a cessation rate of 50% after 8 months among HIV-positive smokers (Wewers et al., 2000
). Another study using cellular telephones for counseling among HIV-positive smokers increased cessation rates to 37% compared with 10% in the usual care group (Vidrine et al., 2006
), results that are very similar to a study of HIV-negative patients utilizing telephone intervention (An et al., 2006
). Further studies are needed to determine whether smoking cessation at any point results in improved outcomes in HIV-positive as in HIV-negative patients (Doll, Peto, Boreham, & Sutherland, 2004
; Kawachi et al., 1993
Our study has certain limitations. Whether smoking has greater attributable mortality in HIV-positive than in HIV-negative patients remains unclear, as our results may be due to fewer events in our HIV-negative sample and interaction terms between HIV and smoking were not significant in our models. Further analyses with longer follow-up time and greater statistical power are needed to address this question. Also, although we adjusted for baseline smoking status, CD4 count, HIV viral load, and use of ART, we did not have data to adjust for changes in these or other measures over time.
This study does not allow us to assess how mortality rates may vary in more recent quitters compared with those who quit in the distant past, as we did not collect data to adjust for the length of time since quitting. Those who have quit more recently may have worse outcomes in the short term, consistent with an “ill-quitter” phenomenon described previously (Kawachi et al., 1993
). However, if we misclassified some subjects who had quit recently as former smokers when they were more representative of current smokers, this potential misclassification would likely have biased us away from finding an association between current smoking and increased mortality. This may also be a potential factor in the increased mortality observed among White subjects, as we do not know whether a greater proportion of Whites might be recent quitters compared with other racial/ethnic groups.
Our findings warrant further study. What mechanisms and diseases account for the increased mortality in smokers with HIV infection are not known. Although we adjusted for potential confounders and measured differences between groups, such as the greater prevalence of hepatitis C among HIV-positive smokers, residual confounding or other unmeasured behaviors that co-vary with smoking may be possible. Whether the excess mortality is due to smoking-related, AIDS-related or non-AIDS related diseases is currently under investigation. Additional investigations from the Women’s Interagency HIV Study suggest that women smokers who are HIV-positive may experience a poorer viral and immunologic response to HAART (Feldman et al., 2006
). It is unclear whether a decreased virologic response to HAART among current smokers might be contributing to the increased mortality in our predominantly male population. We plan further longitudinal studies to assess the relationship between smoking status, HIV viral load, and other time-varying covariates with outcomes.
In summary, we found that current cigarette smoking at study enrollment was associated with significantly increased mortality for HIV-positive patients. Mortality was also increased in HIV-positive patients according to any pack-years of exposure to cigarette smoking. The impact of smoking on mortality was accentuated in the HIV-positive patients when contrasted to the HIV-negative patients. These findings underscore the need to devise effective strategies to promote successful smoking cessation among HIV-positive populations and for studies of mechanisms and diseases underlying increased mortality in smokers with HIV.