Antiretroviral-treated people lose more years of life to smoking than to HIV.

Smoking doubled the death rate in a study of 17,995 antiretroviral-treated * people with HIV in Europe and the United States. (1) People who quit smoking had a death rate similar to that of people who never smoked. The researchers calculated that a 35-year-old HIV-positive smoker would lose 8 years of life because of smoking, compared with 6 years lost because of HIV infection.

Compared with the general population, a higher proportion of HIV-positive people smoke. The Centers for Disease Control and Prevention (CDC) calculates that 42% of HIV-positive people in care in the United States smoke, compared with 21% of the general US population. (2) Smoking takes a tremendous toll on health. It can cause heart disease, stroke, lung cancer and other cancers, and lung disease--all of which can be deadly. In North America and Europe in 2010, smoking was the leading cause of disease in the general population. (3)

As people live to older ages thanks to antiretroviral therapy, age-related diseases like cardiovascular disease and cancer are becoming major causes of death. Different groups of risk factors can contribute to the risk of cardiovascular disease and cancer seen in people with HIV, including HIV itself (through inflammation and immune-system activation), certain antiretroviral drugs, and traditional risk factors (like smoking). Better understanding of which risks are the most important factors for specific diseases can help create strategies to prevent and manage those diseases in people with HIV.

Recent research involving all HIV-positive people in Denmark found that smoking contributed to more than 60% of deaths in these people. (4) This study also found that a 35-year-old HIV-positive man who smokes would lose more years of life because of smoking than because of HIV infection. Researchers who conducted that study teamed up with researchers in other countries to see if the same findings held true throughout Europe and the United States.

* How the study worked. This analysis combined findings from eight HIV study groups (cohorts) in Europe and the United States that had data necessary for an analysis of how smoking affects death rates in people with HIV. From each of these eight cohorts, individuals could be included in the analysis if they (1) started antiretroviral therapy between January 1996 and December 2008, (2) were alive 365 days after starting antiretroviral therapy, (3) had data on smoking status, and (4) did not inject illegal drugs.

The researchers determined who died during the study period by checking national death records, cohort records, and physician reports. They identified a cause for each death with a computer method developed by French HIV researchers. The research team attributed death to AIDS if a person had a serious AIDS illness or a CD4 count below 100 close to the time of death. They classified all other deaths as non-AIDS deaths. The investigators used cohort data to classify each individual as a smoker or a nonsmoker. In certain groups they could classify people as a current smoker, a former smoker, or a never smoker.

Follow-up time (the study period for each person) began when a person's smoking status was determined or 365 days after antiretroviral therapy began, whichever came later. After 365 days of antiretroviral therapy, the CD4 count has usually risen substantially and death from AIDS has become rare. Follow-up time ended when (1) a person died or dropped out of care, (2) 180 days after the last medical visit, or (3) at the end of 2009, whichever came first.

The researchers used mortality rate ratios to compare death rates in smokers and nonsmokers. This type of analysis weighs the impact of standard death risk factors like age and sex (male or female) and HIV-specific risk factors (like CD4 count and time taking antiretroviral therapy). The research team used standard statistical techniques to calculate life expectancy (how long a person is expected to live) for men and to determine excess mortality caused by smoking. They did not figure life expectancy for women because too few nonsmoking women died during the study period to permit that analysis. The investigators compared mortality in HIV-positive men with mortality in the French general population of men.

* What the study found. The study focused on 17,995 HIV-positive people from eight groups, two in France and one each in Italy, Switzerland, the Netherlands, Germany, the United Kingdom, and the United States. Men made up 71% of the entire study group, 71% had a viral load below 400 copies, and 56% had a CD4 count above 350. In three cohorts the researchers classified 9476 participants as smokers or nonsmokers, and in five cohorts they classified 8519 participants as current smokers, former smokers, or never smokers.

Smokers had a median age of 40 years, compared with 38 years among nonsmokers. Men made up 81% of smokers and 57% of nonsmokers. Gay or bisexual men made up a much larger proportion of smokers (45%) than nonsmokers (30%). Heterosexual women made up a smaller proportion of smokers (18%) than nonsmokers (40%).

Everyone had taken antiretroviral therapy for at least 1 year when follow-up began. During a median study period of about 4 years, rates of death from all causes were 7.9 per 1000 person-years among smokers and 4.2 per 1000 person-years among nonsmokers. (A rate of 7.9 per 1000 person-years means about 8 of every 1000 people died every year.) Statistical analysis comparing smokers with nonsmokers determined that smokers had a twice higher death rate (mortality rate ratio 1.94) (Figure 1). When the researchers focused on current smokers, former smokers, and never smokers, they determined that current smokers had a 70% higher death rate than never smokers (mortality rate ratio 1.70). But the death rate did not differ significantly between former smokers and never smokers.

The researchers classified 29% of deaths as AIDS deaths and 71% as non-AIDS deaths. Compared with nonsmokers, smokers had a 2.6 times higher rate of non-AIDS deaths (Figure 2). Smokers had more than a 3 times higher rate of death from non-AIDS cancers, more than a 6 times higher rate of death from cardiovascular disease, and almost a 9 times higher rate of death from liver disease (Figure 2). Thirty-four smokers and no nonsmokers died of lung cancer.

Compared with nonsmokers, smokers had an average 8-year shorter life expectancy. A 35-year-old man with HIV lost an average 5.9 years of life because of HIV infection compared with a 35-year-old man in the general population (Figure 3). Among 35-year-old HIV-positive men, smokers lost an average 7.9 years of life compared with nonsmokers. In other words, in this study population, smoking shortened life 2 years more than HIV infection in 35-year-old men (7.9 - 5.9 = 2.0). Among 65-year-old men, smoking shortened life by 6.6 years, while HIV infection shortened life by only 2.9 years, almost a 4-year difference.

Finally, excess mortality related to smoking increased sharply with age--more than excess mortality related to HIV factors. This means that as HIV populations in Europe and the United States grow older, increases in smoking-related mortality can be expected.

* What the results mean for you. This study of almost 18,000 HIV-positive people in Western Europe and the United States confirmed that smoking has a dramatic negative impact on survival. In fact, this 4-year analysis found that smoking shortens survival in these antiretroviral-treated people more than HIV itself. The study made these key findings:

* Smokers had a twice higher death rate than nonsmokers.

* People who quit smoking did not have a higher death rate than people who never smoked.

* Compared with nonsmokers, smokers had a 3 times higher death rate from cancer and a 6 times higher death rate from heart disease.

* Life expectancy was an average 8 years shorter in smokers than nonsmokers.

* A 35-year-old man with HIV can expect to lose 8 years of life because of smoking.

* A 65-year-old man with HIV can expect to lose more than 6 years of life because of smoking.

* Smoking shortens life more than HIV infection does in people taking antiretroviral therapy.

The finding that HIV-positive people who quit lived as long as people who never smoked is highly encouraging. It should motivate HIV-positive smokers to find a way to quit. No one pretends that quitting is easy, but many long-time smokers do manage to quit. Since 2002, the United States has had more people who quit than people who continue smoking. (5) Visit the link at reference 6 below for more advice on how to quit smoking, including tips from former smokers. An Internet-based smoke-ending program, Positively Smoke Free, has helped HIV-positive people quit. Visit the link at reference 7 below.

According to the CDC, research shows that quitting smoking has the following health benefits: (5)

* Lower risk of lung cancer and many other types of cancer

* Reduced risk of coronary heart disease within 1 to 2 years of quitting

* Reduced risk of stroke and peripheral blood vessel disease

* Reduced risk of chronic obstructive pulmonary disease, a leading cause of death in the United States

* Reduced risk of infertility in women

References

(1.) Helleberg M, May MT, Ingle SM, et al. Smoking and life expectancy among HIV-infected individuals on antiretroviral therapy in Europe and North America. AIDS. 2015;29:221-229.

(2.) Mdodo R, Frazier E, Mattson C, Sutton M, Brooks J, Skarbinski J. Cigarette smoking among HIV+ adults in care: Medical Monitoring Project, US, 2009. 20th Conference on Retroviruses and Opportunistic Infections. March 3-6, 2013. Atlanta. Abstract 775.

(3.) Lim SS, Vos T, Flaxman AD, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2224-2260.

(4.) Helleberg M, Afzal S, Kronborg G, et al. Mortality attributable to smoking among HIV-1-infected individuals: a nationwide, population-based cohort study. Clin Infect Dis. 2013;56:727-734.

(5.) Centers for Disease Control and Prevention. Smoking and tobacco use. Quitting smoking. http://www.cdc.gov/tobacco/data_statistics/fact_sheets/cessation/quitting/index.htm

(6.) Centers for Disease Control and Prevention. Smoking and tobacco use. How to quit. http://www.cdc.gov/tobacco/quit_smoking/how_to_quit/index.htm

(7.) Positively Smoke Free. https://www.positivelysmokefreeme.com/

* Words in bold are defined in the Technical Word List at the end of this issue of HIV Treatment Alerts.

Figure 1. A 17,995-person analysis of HIV-positive people
in Europe and the United States determined that
smokers had almost a twice higher death rate than nonsmokers.
In a separate analysis of current smokers, former
smokers, and never smokers, current smokers had
a nearly twice higher death rate than never smokers. But
the death rate was similar in former smokers and people
who never smoked.

Death rate over 4 years in
smokers vs nonsmokers

Smokers vs         1.94 (almost twice higher rate)
nonsmokers

Current vs never   1.70 (70% higher rate)
smokers

Former vs never    0.92 (essentially no difference)
smokers

Note: Table made from bar graph.

Figure 2. Compared with HIV-positive nonsmokers,
HIV-positive smokers in Europe and the United States
had more than a twice higher death rate from all non-AIDS
diseases over 4 years, a 3 times higher death rate
from non-AIDS cancers (including lung cancer), more
than a 6 times higher death rate from cardiovascular
disease, and nearly a 9 times higher death rate from
liver disease.

Non-AIDS death rates in
smokers vs nonsmokers

Higher death rate in           Mortality rate ratio
smokers versus nonsmokers   (times) higher death rate)

All non-AIDS                        2.6
deaths

Non-AIDS                            3.1
cancer

Heart                               6.3
disease

Liver disease                       8.7

Note: Table made from bar graph.

Figure 3. In an analysis of 12,832 HIV-positive men in
Europe and the United States, smoking accounted for
more life years lost than HIV itself in 35-year-old men
and 65-year-old men.

Impact of smoking and HIV on life years lost
in HIV-positive emn

35-year-old men   years lost

HIV impact          5.9
Smoking impact      7.9

65-year-old men

HIV impact           2.9
Smoking impact       6.6

Note: Table made from bar graph.

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