Shortly after gaining entry to the body and infecting the cells of the immune system that it encounters, HIV causes profound changes to the immune system. The initiation of potent combination anti-HIV treatment (ART) generally reduces the amount of HIV in the blood to very low levels (commonly called “undetectable”), raises the levels of CD4+ cells in the blood, and improves overall health. These benefits of ART are so profound that researchers increasingly expect that many ART users will have a near-normal life expectancy.

One of the problems caused by HIV infection is persistent inflammation and activation of the immune system. These effects of HIV are only partially reduced with ART, thus inflammation and immune activation become chronic. As cells of the immune system are distributed and can travel around the body and even spend time in different tissues/organ-systems, the inflammation and activation caused by HIV can have an impact outside of the immune system. For instance, among HIV-negative people, scientists have found some evidence that chronic inflammation may play a role in the following conditions:

• cardiovascular disease
• degenerative conditions of the brain (such as Alzheimer’s and Parkinson’s diseases)
• type 2 diabetes
• inflammatory diseases of the digestive tract (such as Crohn’s disease)
• arthritis
• psoriasis

It is also possible that chronic immune activation in HIV infection has the potential to gradually weaken and prematurely age the immune system.

Taken together, some scientists suggest that excess inflammation and immune activation in ART users has the potential to increase their risk for the growth and development of abnormal cells, pre-cancers and cancers of the kind that are relatively common in HIV-positive people today. One such cancer is lung cancer.

Smoking tobacco

Tobacco smoking can cause many harms, including increasing the risk for lung and other cancers. Surveys have found that rates of tobacco use are relatively high among HIV-positive people. In the current era, studies have found that HIV-positive people who smoke tend to have diminished life expectancy from smoking-related complications, not from HIV.

Benefits of quitting

Among HIV-negative people, smoking cessation has been found to result in many health-related benefits, including reduced risk of lung and other smoking-related cancers and reduced risk of death. However, these benefits may take some time to appear. For instance, scientists estimate that in HIV-negative people who quit smoking it takes between five and nine years to observe a significant reduction in lung cancer risk.

Brought to you by DAD

Scientists with a large database called DAD have been collecting health-related information from HIV-positive people in Australia, Europe and the United States. DAD scientists assess this data and regularly publish reports about different outcomes of HIV-related issues. In their latest analysis, DAD scientists focused on comparing rates of cancers between people who smoked and subsequently quit and people who never smoked.

The scientists found that the risk for all cancers, including smoking-related ones, was greatest in the first year after quitting. Subsequent risk for some cancers declined, though the risk of lung cancer remained elevated five years after people had quit. To reduce smoking-related complications, the DAD scientists encourage increased efforts to deter initiation of tobacco smoking and enhanced efforts at smoking cessation among HIV-positive people.

Although DAD has about 50,000 participants, scientists focused on data from 35,442 people who had a profile suitable for the present study. These data were analysed from January 2004 to February 2016.

DAD scientists focused on the following outcomes:

• diagnosis of any new cases of cancer
• diagnosis of a first episode of lung cancer
• diagnosis of any smoking-related cancer, which were listed as: cancers of the head and neck, throat, stomach, pancreas, liver, bladder, kidney and urinary tract, colon and rectum, cervical, ovary, acute myeloid leukemia and chronic myeloid leukemia
• non-smoking-related cancers

Overall, participants were monitored for up to 10 years.

The average profile of participants was as follows:

• age – 40 years
• 73% men, 27% women
• CD4+ count – 444 cells/mm³
• 52% of participants were on ART and most of them had a viral load that was undetectable

The distribution of participants by smoking status was as follows:

• 49% current smokers
• 21% ex-smokers
• 30% never smoked

Results

All cancers

During the first year after smoking cessation, rates of all cancers increased by 28% among smokers vs. non-smokers. Subsequently, the greater the length of time that a person had quit smoking, the lower their risk of developing any cancer.

Lung cancers

In the first year after quitting, rates of lung cancer were 19-fold higher in smokers than in non-smokers. Subsequently, the rate of lung cancer fell but was still eight-fold higher in smokers than non-smokers five years after smokers had quit. After this time point, there were not sufficient cases of lung cancer to draw meaningful conclusions.

Other smoking-related cancers

As with the other cancers, the rate of other smoking-related cancers was high in the first year after quitting, but then fell to the same level seen in non-smokers.

Cancers unrelated to smoking

DAD scientists did not find any connection between smoking and the rate of cancers unrelated to smoking.

In the first year after quitting

Research with HIV-negative people has found that rates of lung cancer are also high in the first year after quitting. The DAD scientists suggested that cancers in the present study that occurred in the first year after quitting were the culmination of tumour growth and development. However, they also noted that other factors likely played a role in the first year after quitting.

Some, perhaps many, people in the study may have quit smoking because they were “unwell either because of their undiagnosed (subclinical) cancer or because of another condition (such as chronic obstructive pulmonary disease, or COPD), which may subsequently lead to a cancer diagnosis due to increased intensity of medical surveillance.” The DAD scientists suggested that even among people without COPD who had quit smoking, there may have been more contact with the medical-healthcare system because of other illnesses. This contact could ultimately have led to the discovery of a tumour(s).

Cancer cases

The distribution of cancer in the DAD study was as follows:

• total number of cancers – 2,183 people
• number of cases of lung cancer – 271 people
• number of cases of other smoking-related cancers – 622 people
• number of cases of cancers unrelated to smoking – 1,290 people

Bear in mind

DAD scientists noted that there were only 12 cases of cancer that were diagnosed more than five years after participants had quit. This small number is insufficient to draw statistically robust conclusions about the long-term cancer risk among quitters.

DAD scientists stated that there may be other reasons that HIV-positive smokers are at elevated risk for lung cancer, such as the following:

• Levels of inflammation are elevated in HIV infection in general, and in the lungs in particular. This may increase the risk for the development of abnormal cells.
• The functioning of the immune system is partially weakened because of HIV-associated chronic inflammation and immune activation. This may impact the immune system’s ability to detect and destroy cancer cells.
• Low-level production of HIV and associated proteins deep within the body, including the lungs, may contribute to an increased risk of lung cancer.

For the future

The DAD analysis was imperfect; it did not have information about the number of cigarettes smoked per day or about how many years people had been smoking before they developed cancer. Despite this, its findings are a step forward.

The results from DAD underscore the need for doctors, nurses and pharmacists to help their HIV-positive patients quit smoking. At a societal level, the DAD findings are a reminder that public health authorities and politicians need to do more to help prevent susceptible people from taking up smoking.

The DAD analysis also points to a future direction for research, care and treatment. There is a continued need to intensify awareness for lung cancer screening among smokers and ex-smokers.

As more researchers expect HIV-positive people to have a near-normal life expectancy, scientific agencies that fund research need to provide the money for long-term monitoring, so that observational studies such as DAD and smaller ones within high-income countries can continue.

Resources

Smoking, addiction and breaking free

• How to Say “I Quit”—and Mean It – The Positive Side
• Smoking and tobacco – Canadian Cancer Society
• How to Quit Smoking – The Lung Association
• Understanding tobacco addiction – CATIE News
• Varenicline—An Ontario study assesses safety in HIV-positive people – CATIE News
• Smoking cessation: Innovative group therapy–centered support found to double quit rate – CATIE News
• Danish study underscores link between heart attacks and smoking – CATIE News

Cancer

• Canada–U.S. study looks at age when cancer appears in HIV – CATIE News
• Lung cancer risk linked to immunological dysfunction and bacterial pneumonia – CATIE News
• Study finds shift in cancers as HIV-positive people age – CATIE News
• Euro-Canadian study looks at trends in liver cancer in co-infected people – CATIE News
• Canadian Cancer Society

—Sean R. Hosein

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