Impact of smoking on life expectancy in HIV infection
By Gareth Hardy, HIV i-Base
Smoking may double the risk of mortality for HIV positive people according to results from a large collaborative HIV cohort study of people who have been on ART for more than one year.
This is according to results presented by Marie Helleberg and colleagues from the University of Copenhagen in Denmark, and publish in the January issue of AIDS. 
Helleberg et al show that while the life expectancy of a non-smoking, HIV positive, 35 year-old male with a CD4 count above 200 and viral load below detection for more than one year, is similar to that of the general population, the life expectancy of a similar male who smokes is 8 years shorter. These results confirm those of a previous study that investigated smoking-associated mortality in HIV positive people in Denmark. 
The investigators presented data on 17,995 HIV positive individuals, from eight different cohorts in Europe and North America, who were followed for 79,760 person years. In three cohorts, individuals were categorised as smokers (current or previous) or non-smokers. In the remaining five cohorts, individuals were categorised in more detail as current, previous or never smokers. In order to calculate the number of life years lost due to HIV, the life expectancy in the cohorts was compared to that of the male general French population. The study lacked statistical power to determine life expectancy in women, therefore the results on loss of life years and life expectancy can only be extended to the male population.
HIV positive individuals were eligible for inclusion in the analysis if they started ART (with at least 3 drugs), were alive and under follow up 365 days after ART initiation, and had data on smoking status. Follow up for each person began at the time that smoking status was determined or 365 days after starting ART, which ever was later. 71.3% were men, 70.6% had a viral load below 400 copies/ml and 56.2% had a CD4 count above 350 cells/mm3 at baseline.
The investigators estimated excess mortality rates using a formula where the mortality rate of smokers was subtracted from the mortality rate of non-smokers. Mortality rate ratios were calculated using Poisson regression analysis adjusted for sex, age, mode of HIV transmission, year of ART-initiation, years on ART, CD4 count at baseline and AIDS at ART initiation.
The all-cause mortality rate for smokers was 7.9 per 1000 person years (95%CI: 7.2-8.79) and for non-smokers was 4.2 (95%CI: 3.5 – 5.0) and the adjusted mortality rate ratio (MRR) for smokers versus non-smokers was 1.94 (96%CI: 1.56 – 2.41). When individuals were stratified according to sex, route of HIV transmission, CD4 count or viral suppression at baseline, it did not affect the MRR of smokers versus non-smokers.
Cause of death could be determined for 90% of 520 cases. Out of those cases, AIDS-related causes of death were determined for 29% of cases with a mortality rate of 1.6 per 1000 person years (95%CI: 1.3 – 1.9). Non-AIDS related causes of death were determined for the remaining 71% of cases with a mortality rate of 4.6 per 1000 person years (95%CI: 4.2 – 5.1). In smokers the rate of non AIDS-related deaths was higher than in non-smokers with a MRR of 2.61 (95%CI: 1.88 – 3.61).
Assessment of the rates of death by specific causes further revealed significant differences between smokers and non-smokers. Comparing smokers with non-smokers the rates of non AIDS-related deaths were significantly higher with a MRR of 2.61 (95%CI: 1.88 – 3.61), in which deaths related to cardiovascular disease, non-AIDS malignancies and liver disease were all significantly higher in smokers. Lung cancer accounted for 36% of non-AIDS malignant deaths, and occurred exclusively in smokers. Of the non-AIDS malignant deaths, 50% were due to cancers associated with smoking and 96% of those occurred in smokers.
Smoking also had a substantial effect on life expectancy. The number of life years lost was calculated for each age bracket from 25-65, in 10-year intervals. Data for those above 65 were pooled. The greatest reduction in life years was observed for younger cohort participants. The investigators speculate that this is partly because the health impacts of smoking only manifest after several years of exposure and partly because middle and older age persons are less likely to take up smoking. Life expectancy for HIV positive men aged 35 was found to be 5.9 years shorter (95%CI: 4.9 – 6.9) than the same age bracket in the general population. In contrast life expectancy for HIV positive smokers in this age bracket was found to be 7.9 years (95%CI: 7.1 – 8.7) shorter. For those aged over 65 the loss of life years associated with HIV was 2.9 years and the loss of years associated with smoking was 6.6 (95%CI: 6.0 – 7.2) years. Therefore while the number of life years lost due to HIV-infection declines with from the 35 years age bracket to 65 years, the number of life years lost due to smoking remains fairly constant. When the investigators looked at excess mortality rates associated with smoking or HIV-infection, they both increased with age. However the increase in excess mortality rate that occurs with age, was much greater in association with smoking than with HIV-associated factors.
In this study, smoking was associated with a two-fold increase in mortality rate, and the excess mortality rate in smokers was mostly accounted for by non-AIDS malignancies and cardiovascular disease. The investigators point out that their observation that the risk of death in previous smokers is substantially lower than that in present smokers, suggests that smoking cessation programs may have potential benefits in HIV care. While this study had limited data on the effects of current versus previous smoking, the investigators have shown in a different study that previous smokers had similar mortality rates to those who had never smoked. 
In addition, the rate of cardiovascular disease in HIV positive individuals greatly decreases with time since ceasing smoking. 
The results of these studies contrasts with those conducted in the pre- or early-ART era, which found that there was little impact of smoking on mortality in HIV positive people. 
The investigators of this study suggest this is because the reduction in life years lost to AIDS has steadily diminished as the ART era has progressed, while at the same time the impact of smoking and other life-style risk factors is likely to increase, as HIV positive people live longer and age.
- Helleberg M et al. Smoking and life expectancy among HIV-infected individuals on antiretroviral therapy in Europe and North America. AIDS (14 January 2015), 29: 221 – 9.
- Helleberg m et al. Mortality attributable to smoking among HIV-1-infected individuals: a nationwide, population-based cohort study. Clin Infect Dis (2013), 56:727–734.
- Petoumenos K, et al. Rates of cardiovascular disease following smoking cessation in patients with HIV infection: results from the D:A:D study(M). HIV Med (2011), 12:412–421.
- Galai N, et al. Effect of smoking on the clinical progression of HIV-1 infection. J Acquir Immune Defic Syndr Hum Retrovirol (1997), 14:451–458.