Prolonged HIV viremia is an independent risk factor for non-Hodgkin lymphoma – antiretroviral therapy crucial in preventing non-Hodgkin lymphoma

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A research team led by the Yale School of Public Health has found that for people living with HIV/AIDS, both recent immunosuppression (a low recent CD4 T-cell count [white blood cells that fight infection]) and prolonged HIV viremia (the presence of HIV in the blood) play important and independent roles in the development of non-Hodgkin lymphoma.


What Is Non-Hodgkin Lymphoma?

Cancer starts when cells begin to grow out of control. Cells in nearly any part of the body can become cancer, and can spread to other areas.

Non-Hodgkin lymphoma (also known as non-Hodgkin’s lymphoma, NHL, or sometimes just lymphoma) is a cancer that starts in white blood cells called lymphocytes, which are part of the body’s immune system.

  • NHL is a term that’s used for many different types of lymphoma that all share some of the same characteristics. There is another main type of lymphoma, called Hodgkin lymphoma, which is treated differently.
  • NHL most often affects adults, but children can get it too.
  • NHL usually starts in lymph nodes or other lymph tissue, but it can sometimes affect the skin..

Where lymphoma starts

Lymphoma affects the body’s lymph system (also known as the lymphatic system). The lymph system is part of the immune system, which helps fight infections and some other diseases. It also helps fluids move through the body.

Lymphomas can start anywhere in the body where lymph tissue is found. The major sites of lymph tissue are:

  • Lymph nodes: Lymph nodes are bean-sized collections of lymphocytes and other immune system cells throughout the body, including inside the chest, abdomen, and pelvis. They are connected by a system of lymphatic vessels.
  • Spleen: The spleen is an organ under the lower ribs on the left side of the body. The spleen makes lymphocytes and other immune system cells. It also stores healthy blood cells and filters out damaged blood cells, bacteria, and cell waste.
  • Bone marrow: The bone marrow is the spongy tissue inside certain bones. This is where new blood cells (including some lymphocytes) are made.
  • Thymus: The thymus is a small organ behind the upper part of the breastbone and in front of the heart. It’s important in the development of T lymphocytes.
  • Adenoids and tonsils: These are collections of lymph tissue in the back of the throat. They help make antibodies against germs that are breathed in or swallowed.
  • Digestive tract: The stomach, intestines, and many other organs also have lymph tissue.
Illustration showing the lymphatic system in the body

Types of non-Hodgkin lymphoma

Treatment for NHL depends on which type it is, so it’s important for doctors to find out the exact type of lymphoma you have.

The type of lymphoma depends on what type of lymphocyte is affected (B cells or T cells), how mature the cells are when they become cancerous, and other factors. 

B-cell vs T-cell lymphomas

The lymph system is made up mainly of lymphocytes, a type of white blood cell that helps the body fight infections. There are 2 main types of lymphocytes:

  • B lymphocytes (B cells): B cells normally help protect the body against germs (bacteria or viruses) by making proteins called antibodies. The antibodies attach to the germs, marking them for destruction by other parts of the immune system.
  • T lymphocytes (T cells): There are several types of T cells. Some T cells destroy germs or abnormal cells in the body. Other T cells help boost or slow the activity of other immune system cells.

Lymphoma can start in either type of lymphocytes, but B-cell lymphomas are most common.

Indolent vs. aggressive lymphomas

Types of NHL can also be grouped based on how fast they grow and spread:

  • Indolent lymphomas grow and spread slowly Some indolent lymphomas might not need to be treated right away, but can be watched closely instead. The most common type of indolent lymphoma in the United States is follicular lymphoma.
  • Aggressive lymphomas grow and spread quickly, and usually need to be treated right away. The most common type of aggressive lymphoma in the United States is diffuse large B cell lymphoma (DLBCL).
  • Some types of lymphoma, like mantle cell lymphoma, don’t fit neatly into either of these categories.

Regardless of how quickly they grow, all non-Hodgkin lymphomas can spread to other parts of the lymph system if not treated.

Eventually, they can also spread to other parts of the body, such as the liver, brain, or bone marrow.

Classifying types of NHL

There are many different types of non-Hodgkin lymphoma (NHL), so classifying it can be quite confusing (even for doctors).

Several different systems have been used, but the most recent system is the World Health Organization (WHO) classification. The WHO system groups lymphomas based on: 

  • The type of lymphocyte the lymphoma starts in
  • How the lymphoma looks under a microscope
  • The chromosome features of the lymphoma cells
  • The presence of certain proteins on the surface of the cancer cells

Furthermore, the team observed differences across non-Hodgkin lymphoma subtypes.

The study is believed to be the largest to comprehensively evaluate a variety of measures of T-cell count and viral load to determine the key predictors of risk for non-Hodgkin lymphoma, both overall and by its subtypes.

Since the early days of the AIDS epidemic, HIV infection has been strongly associated with the development of two types of cancer: non-Hodgkin lymphoma and Kaposi sarcoma.

The study, published in The Lancet HIV journal, examined people living with HIV from 1996 to 2014 from the United States and Canada, comprising more than 100,000 individuals, of which 712 patients were diagnosed with non-Hodgkin lymphoma.

Using models, researchers solidified earlier evidence suggesting that recent T-cell count and cumulative viral load both play important and independent roles in the development of non-Hodgkin lymphoma, and generated new evidence regarding their roles in the development of non-Hodgkin lymphoma subtypes.

“Our finding that prolonged HIV viremia is an independent risk factor for non-Hodgkin lymphoma reinforces the importance of early diagnosis of HIV infection followed by prompt initiation of antiretroviral therapy (ART),” said Raul U. Hernandez-Ramirez, Ph.D., an associate research scientist in biostatistics at the Center for Methods in Implementation and Prevention Science at the Yale School of Public Health.

“Curtailing chronic HIV viremia and restoring immune function with early and sustained ART is crucial for preventing non-Hodgkin lymphoma.”

Despite the sharp decline in the risk for non-Hodgkin lymphoma in people living with HIV after the introduction of effective ART, risk for those patients is still substantially higher than in the general population, most likely because of late HIV treatment initiation and because the treatment does not completely restore immunological health, said Hernandez-Ramirez. Moreover, the incidence trends and the principal reasons for the increased risk for non-Hodgkin lymphoma vary by subtype.

Therefore, additional efforts aimed at optimizing early HIV diagnosis and prompt and sustained HIV treatment are warranted to further prevent overall non-Hodgkin lymphoma.

Additional research is needed as wellto better understand the etiology of each subtype of non-Hodgkin lymphoma.

More information: Raúl U Hernández-Ramírez et al. Association of immunosuppression and HIV viraemia with non-Hodgkin lymphoma risk overall and by subtype in people living with HIV in Canada and the USA: a multicentre cohort study, The Lancet HIV (2019). DOI: 10.1016/S2352-3018(18)30360-6
Provided by Yale University

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