Ontario study links low T-cell counts to increased risk for certain cancers in people with HIV

• Heightened cancer risk remains for some people with HIV despite effective HIV treatment
• A 23-year Ontario study with 4,771 people with HIV found an increased risk of some cancers
• Many steps (such as screening) can be taken to help lower cancer risk in people with HIV 

When initiated and used as directed, HIV treatment (antiretroviral therapy, ART) greatly reduces the amount of HIV in the blood of most people within three to six months. Continued use of ART helps to keep HIV suppressed to very low levels commonly called “undetectable.” Suppression of HIV allows the immune system to mostly repair the injury caused by this virus. This effect of ART is so powerful that the risk of AIDS-related infections and cancers is greatly reduced. What’s more, researchers increasingly project that many ART users will have near-normal life expectancy.

However, ART cannot solve every issue related to HIV. For instance, chronic HIV infection is associated with persistent and elevated levels of inflammation and immune activation. By suppressing HIV levels, ART helps to decrease inflammation and immune activation, but it does not normalize them. 

Risks with inflammation

Studies in people without HIV suggest that chronic inflammation likely contributes to an increased risk for the following:

• cardiovascular disease
• cancer
• type 2 diabetes
• degenerative conditions of the brain
• fat accumulation in the liver
• thinning bones
• loss of muscle tissue
• high cholesterol levels
• premature aging of the immune system

It is therefore possible that chronic inflammation associated with HIV contributes to an increased risk for these same issues in people with HIV.

The underlying drivers of persistent excess inflammation and immune activation in people with HIV may be related to at least the three following factors:

• chronic low-level infection with cytomegalovirus (CMV) – a member of the herpes family of viruses
• the passage of proteins from bacteria and fungi in the digestive tract to the blood
• the production of low levels of HIV proteins deep within the immune system and brain

Other possible drivers of cancer risk in people with HIV include the following:

• coinfection with viruses such as Epstein Barr Virus (EBV), Kaposi’s sarcoma virus, hepatitis B virus (HBV), hepatitis C virus (HCV) and human papillomavirus (HPV)
• use of tobacco, excess alcohol consumption and drug use

Study details

A team of researchers at several universities in Ontario and at the Ontario HIV Treatment Network (OHTN) developed a study to analyze cancer risk. The researchers focused on people with HIV who were diagnosed with a new case of cancer between 1997 and 2020. Researchers considered the overall health of the immune systems of participants when conducting their analysis, focusing on T-cell counts (CD4+ and CD8+ cells).

The researchers divided the cancers that people developed into the following two groups: 

• infection-related cancers (caused by different viruses and bacteria) – Kaposi’s sarcoma; lymphoma; cancers of the anus, genitals, head and neck; cancers affecting the liver, nose and stomach
• infection-unrelated cancers – cancers of the bladder, brain, breast, blood, colon/rectum, throat, lung, skin (melanoma), ovary, pancreas, prostate, testis, thyroid and uterus

The study analyzed health-related information from 4,771 people with HIV; they developed 549 cases of cancer. 

Upon entering the study, a brief average profile of participants was as follows:

• age – 41 years
• most participants were male (84%) and white (68%)
• 84% were long-term residents of Canada 
• 67% had a suppressed viral load (defined as less than 50 copies/mL of blood)

Results

The average age at which cancer was diagnosed was 52 years. The distribution of cancers was as follows:

• infection-related – 266 cases
• infection-unrelated – 283 cases

There were 487 cancer diagnoses among male participants. The most common were as follows:

• non-Hodgkin’s lymphoma – 16%
• anal cancer – 11%
• prostate cancer – 11%
• lung cancer – 9%
• Kaposi’s sarcoma – 8%
• cancers of the tongue and throat – 7%
• liver cancer – 6%

Among female participants, there were 62 cancer diagnoses. The most common were as follows:

• non-Hodgkin’s lymphoma – 21%
• breast cancer – 16%
• lung cancer – 10%

The immune system and infection-related cancer risk

The immune system helps to detect and destroy viruses, virus-infected cells and cancerous cells. So, it is not surprising that the risk of infection-related cancer was elevated in people with the following:

• a low CD4+ count (less than 200 cells/mm³) upon entering the study – a twofold increased cancer risk
• a CD4+ count that fell below the 200 cells/mm³ threshold at any point during the study – also a twofold increased cancer risk
• a recent CD4+ count that was less than 200 cells/mm³ – a 3.5-fold increased risk of cancer
• a low CD4+/CD8+ ratio (defined as less than 0.4; a normal ratio is generally around 1.0 or higher)

The researchers did not find any association between cancers unrelated to infections and lab measures of the immune system.

What to do?

In general, the findings from the Ontario study are aligned with other studies from Europe and the U.S. Furthermore, the Ontario researchers stated that “overall, independent of sociodemographic, behavioural factors and [year], all CD4 indices of immunosuppression were associated with an increased [risk] of infection-related cancer […].”

To reduce cancer risk in people with HIV, the researchers encouraged the early initiation of ART (before CD4+ cell counts fall to low levels). 

Additional steps that could be taken include the following:

• screen patients for tobacco use and offer support and options for tobacco cessation
• ensure that people with HIV get integrated into screening programs for cancers of the breast, colon/rectum, cervix and lungs
• offer vaccination against HBV
• offer screening and treatment for HCV
• expand subsidies for vaccination against HPV

ART has brought tremendous benefits to people with HIV. However, people with HIV will need access to cancer screening and other programs to help reduce their risk of cancer so that their life expectancy can be equal to those of people without HIV.

—Sean R. Hosein

Resources

Canada–U.S. study looks at age when cancer appears in HIV – CATIE News

French researchers investigate second cancers in people with HIV who survived a first cancer – CATIE News

North American study finds low CD4/CD8 ratio can help predict cancer risk in people with HIV – CATIE News

Looking to letermovir to reduce inflammation and other issues in people with HIV – CATIE News

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