Navigating Through the Challenges of Living With Human Immunodeficiency Virus (HIV) and Lymphomas

T-cells, also known as T lymphocytes, are crucial to the immune system, which combats infection-causing pathogens (such as viruses, bacteria, fungi, and parasites) to eliminate harmful cells, like cancer cells. Human immunodeficiency virus (HIV) infection leads to a gradual decline in the function and number of a special type of T-cells called CD4+ helper T-cells (CD4), leading to increased risk of infections and cancer development, especially lymphoma ( a type of cancer of the lymphatic system).  There are two types of lymphoma: Hodgkin Lymphoma (HL) and non-Hodgkin Lymphoma (NHL)

In 2022, about 39,000,000 people world-wide were infected with HIV. 630,000 died from HIV related illnesses. The relationship between HIV  and lymphoma has been a subject of significant interest in the medical community, as the two conditions are often intertwined, with HIV infection increasing the risk of developing certain types of lymphoma (both HL and NHL) compared with HIV-negative individuals. Among people living with HIV, approximately 25-40 % will develop a malignancy, with approximately 10 % developing NHL. As for other blood cancers, data on the risk of multiple myeloma or leukaemia are inconsistent and of low quality but the risk does not seem to be increased. Following the extensive adoption of HIV antiviral treatment also known as HAART, the risk of NHL initially declined and has since remained stable. Incidence of HL remains stable since 2000.

Fig 1. The common types of lymphomas associated with HIV
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AIDS-defining cancers
AIDS (Acquired Immunodeficiency Syndrome) is the advanced stage of HIV infection that develops when the virus severely damages the body’s immune system. AIDS-defining cancers are the type of cancers that a person infected with HIV is at high risk of developing. If a person with HIV develops one of these cancers, it means they have AIDS. They include Kaposi sarcoma, aggressive B cell NHL, and invasive cervical cancer.

Several types of NHL are AIDS-defining:

• Burkitt’s lymphoma
• Diffuse large B-cell lymphoma (DLBCL)
• Plasmablastic lymphoma
• Primary central nervous system lymphoma.

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Risk factors of HIV-associated lymphomas
Risk factors for HIV-related lymphoma include both HIV-specific risk factors (such as the CD4 cell count and HIV viral load) and more general risk factors known to increase the risk of NHL in patients without HIV.

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Viral load and CD4 count
HIV causes immune deficiency primarily by targeting and destroying CD4+ helper T-cells, which are crucial for the immune system’s ability to fight infections and to detect cancer cells in the body

NHL is primarily encountered in patients with more advanced HIV infection and a CD4 cell count that is usually below 100 cells/microL with high viral load (plasma HIV RNA levels >100,000 copies/mL ). HIV-related Burkitt lymphoma frequently develops in relatively younger patients and when the CD4 count is relatively higher, typically over 200 cells/microL. Primary CNS lymphoma requires a more severe degree of immunosuppression than most other HIV-related complications, as the CD4 counts in affected patients are generally less than 50 cells/microL.

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Effects of HAART
Studies found that the incidence of HIV-associated NHL decreased from 117-fold higher than the general population during the pre-HAART era (1992 to 1996) to ninefold higher in the post-HAART era (2005 to 2009). This is most likely due to reduced viral load and improved CD4 cell counts. However, there is no changes in the incidence and proportion of Hodgkin lymphoma and Burkitt’s lymphoma.

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Genetics and family history
A history of haematopoietic malignancy in any first-degree relative was associated with an increased risk of all NHL. However, the majority of people with lymphoma do not have a significant family history of it. Genetic changes associated with NHL are typically acquired during one’s lifetime rather than inherited.

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Symptoms
Patients may often experience swelling of the lymph glands around the neck, armpit, or groin. Patients may also have lymphoma outside of these lymph glands affecting bone marrow, lung, liver, spleen, oral cavity, central nervous system (i.e., brain) and gut. They may experience B symptoms – a constellation of symptoms which include unexplained fever ((temperature over 38°C), and drenching night sweats (which drench your nightclothes and bedding.) , ≥ 10% of weight loss from the baseline in 6 months

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Treatment
For some patients, the diagnosis of both HIV/AIDS and lymphoma come at the same time. This can be an overwhelming and emotionally challenging experience. While the intersection of HIV and lymphoma presents unique challenges, individuals living with this dual diagnosis can navigate the complexities with determination and resilience if he/she receives a proper comprehensive care. Patients with these two conditions will need a specialised healthcare facility and multi-disciplinary care team, including infectious disease specialists who specialises in HIV medicine, haematologists, allied health and nurses, to provide holistic patient-centred care. A one-stop care service that manages patients’ medical, physical, psychological, social, and emotional aspects at every step of their treatment journey.

A patient will need:

• Anti-HIV treatment (HAART)- continues to be fundamental in HIV treatment by inhibiting viral replication and improving immune function, which is essential and synergistic for lymphoma treatment. However, when integrating HAART with cancer therapies, it is vital to consider several key factors. These include selecting the most optimal anti-cancer treatment regime (such as chemotherapy or radiotherapy) due to the potential for drug interactions, existing medical conditions, and possible adverse drug effects (such as skin rash, gastrointestinal issues, metabolic complications, bone marrow suppression, and peripheral neuropathy).
• Lymphoma treatment- Chemotherapy and radiation therapy are the primary treatments for lymphoma, but their administration must be carefully coordinated with the patient’s HIV status and antiretroviral regimen to minimise adverse interactions and optimise outcomes.
• Treatments for ongoing infections or to prevent future infections include a wide range of antibiotics, antifungals and, antiviral agents, and immunisations at the right time. You might also be monitored to make sure any past infections that could be dormant in your body don’t reactivate.
  Patients who have HIV may have a low white blood cell count (neutropaenia), which may increase the risk of infections. Your physician may give you growth factors (G-CSF) to boost your white blood cell count.
• Supportive Care- Beyond medical treatment, individuals living with HIV and lymphoma often benefit from a range of supportive services, including mental health counselling (SOS), spiritual support (Rainbodhi, CARE), nutritional guidance, and community-based resources that foster a sense of empowerment, resilience, provide valuable peer-to-peer connections, reduce isolation, and foster resilience in the face of the social stigma often associated with HIV/AIDS (AFA, gayhealth, sgprecious)
• Rehabilitation measures and occupational reintegration, facilitated by governmental body ( SNEF ) with multi-disciplinary teams, can play a pivotal role in helping patients successfully reintegrate into daily life and the workforce during or after completion of treatment.

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Outlook and prognosis

Fig 2. Kaplan–Meier plots comparing OS for patients enrolled on trials in different treatment eras. Patients with AIDS-related lymphomas who had (A) DLCBL, (B) BL/BLL, (C) CD4 <50 cells/mm3 or (D) CD4 ≥50 cells/mm3 achieved significantly longer overall survival when treated in later treatment eras. (Adapted from S.K. Barta et al Annals of Oncology 2015)

While the combination of frontline chemo-immunotherapy with HAART has resulted in a remarkable prolongation of the overall survival among patients with HIV and lymphoma, this group of patients are still at risk of poor outcomes and increased deaths compared to non-HIV patients. The successful treatment of HIV/AIDS and lymphoma has been a long-standing challenge in the medical community, with significant advancements made in recent decades. The advent of HAART has transformed HIV/AIDS from a terminal condition to a chronic, manageable disease, allowing individuals to live longer and healthier lives. HIV-infected patients can achieve near-normal life expectancy through modern HAART, provided that they are diagnosed timely, provided good medical care, and can adhere to their HIV treatment.

References

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– Contributed by Dr Lee Chun Tsu