Research on HIV associated cancer

Executive Summary

Several latest research studies have been progressing to seek more information on HIV-associated cancer, related prevention methods, diagnostic process at the initial phase, and best treatment strategies. Recent research studies on some of the immunotherapy techniques for HIV-associated cancer patients involving immune checkpoint inhibitors, further involving cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed cell death ligand-1 (PD-L1), and programmed cell death-1 (PD-1) inhibitors are progressing. Although having high toxicity, T. Genetically modified autologous or allogeneic CAR T cells with specific anti-tumor activity is also an example of a practical approach to cancer therapy. Several studies of autologous SCT have also been performed in patients with various types of lymphoma. However, allogeneic SCT has not been adequately studied in HIV patients. Researchers are also looking at ways to combine antiretroviral medicines with chemotherapy, commonly used to treat AIDS-associated cancer patients.

Newer drugs such as valganciclovir, used to treat herpesviruses associated diseases, such as cytomegalovirus (CMV), may also find their uses in the treatment of KSHV infection. Palliative care helps reduce, prevent, and maximize the physical function and quality of life of critically ill patients. 

Advancement in HIV Associated Cancer

Further research studies are conducted to know more about HIV-associated cancer. The ways to prevent it, the best treatment options, and also how to provide the best care to people diagnosed with this disease. The following research areas may include new options for patients through clinical trials. Hence, it is best to talk to an oncologist about the diagnostic and treatment options for HIV-associated cancer patients.

Immunotherapy

In short, immunotherapy includes a broad category of cancer therapy that triggers the body’s immune system to fight cancer cells. Even so, there are different types of immunotherapies. Some of these are also called targeted or biological therapies. Recent research studies on some of the immunotherapy techniques for HIV-associated cancer patients are discussed below:

Immune checkpoint inhibitors (ICIs)

Research studies are looking into the use of immune checkpoint inhibitors in HIV-associated cancer patients. Immune checkpoints generally reduce the damage caused by a compromised immune response resulting in autoimmune destruction of tissues and organs. These immune checkpoint inhibitors (ICIs) consist of cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed cell death ligand-1 (PD-L1), and programmed cell death-1 (PD-1) inhibitors.

The potential benefits of ICIs in HIV treatment have led to clinical trials to determine their effect in overcoming the compromised immune system due to chronic HIV infection, manifested by persistently low CD4 count and viral suppression. Although previous clinical trials with ICIs for cancer treatment excluded HIV-infected patients, recent retrospective studies have examined the benefit of ICIs in AIDS-related cancer patients. The examination of ICIs shows that they may have benefits in particularly the treatment of HIV. And so, based on limited data, show potential for treatment in HIV-related cancer patients​1​.

In recent years, multiple targeted therapies for Kaposi Sarcoma (KS), especially oral medicines, have been developed. The most encouraging results are of the pomalidomide, an orally available thalidomide derivative that is less neurotoxic and has anti-angiogenic, immune-modulatory, and antiproliferative activities​2​. Activation of tyrosine kinase (TK) receptor c-kit and platelet-derived growth factor (PDGF) has been demonstrated to have a significant role in KS pathogenesis both in vitro and in vivo. Imatinib, a selective inhibitor of the c-kit, and TK Abl have been tested in HIV-KS patients with promising results​3​. Likewise, Rapamycin is effective in the treatment of HIV-KS​4​.

Chimeric antigen receptor T-cell (CAR T) therapy

Genetically modified autologous or allogeneic CAR T cells with specific anti-tumor activity, although having high toxicity, are an example of an effective approach to cancer therapy​5​

The most common toxicities are CAR T-cell-associated encephalopathy syndrome and cytokine release syndrome. These can occur simultaneously and are difficult to distinguish from infection​6​. With increasing management and understanding of CAR T cell therapy complications, the treatment of cancer is also evolving so are the clinical trials for the treatment of HIV-associated cancer.

Stem Cell Transplantation (SCT)

Antiretroviral therapy (ART) provides a well-tolerated day-to-day treatment option with reduced drug-drug interactions and an effective alternative for patients with increased risk for developing hepatic or renal toxicity during cancer treatment, allowing the successful use of allogeneic or autologous SCT in the treatment of AIDS-Related cancer patients​7​. Additionally, several studies of autologous SCT have been performed in patients with various types of lymphoma. Allogeneic SCT has not been adequately studied in HIV patients, but few studies suggest that it is safe in some patients with well-controlled HIV and with adequate initial screening for opportunistic infections at baseline​8​.

Combination therapy

Combination chemotherapy uses multiple drugs (usually given together) for cancer treatment. In addition to multiple chemotherapy regimens, researchers are also looking at ways to combine antiretroviral medicines with chemotherapy, commonly used to treat AIDS associated cancer patients.

Virus research

HIV cancer research continues to learn more about the viruses linked to AIDS-associated cancer. Detection of Kaposi’s sarcoma-associated herpesvirus (KSHV), a virus that helps develop KS in a patient’s body, can help manage patients at risk for KS. This can also include AIDS-associated cancer patients or who are on immune system suppression drugs for undergoing organ transplants. Newer medicines such as valganciclovir, used for the treatment of herpesviruses-associated diseases, such as cytomegalovirus (CMV), may also find their uses in the treatment of KSHV infection. These drugs prevent the replication of more viruses in KSHV-infected cells, however, the drugs are not effective once KS has developed in the patient​9​.

Palliative care

The goals of palliative care are to reduce, prevent, and maximize the physical function and quality of life of critically ill patients. Clinical trials are underway to find better ways to reduce Kaposi’s sarcoma treatments’ side effects and symptoms to improve patient’s well-being and quality of life.

References

  1. 1.
    Granwehr BP. Review: The Impact of HIV Infection on Cancer Treatment with Immunotherapy. Journal of Immunotherapy and Precision Oncology. Published online August 1, 2019:85-92. doi:10.4103/jipo.jipo_14_19
  2. 2.
    Bolanos R, Martinez-Maza O, Zhang Z, et al. Decreased levels of the serum inflammatory biomarkers, sGP130, IL-6, sCRP and BAFF, are associated with increased likelihood of AIDS related Kaposi’s sarcoma in men who have sex with men. Cancer Res Front. 2018;4(1):45-59. doi:10.17980/2018.45
  3. 3.
    Koon H, Bubley G, Pantanowitz L, et al. Imatinib-induced regression of AIDS-related Kaposi’s sarcoma. J Clin Oncol. 2005;23(5):982-989. doi:10.1200/JCO.2005.06.079
  4. 4.
    Dalla P, Pinato D, Bracchi M, Bower M. Recent advances in HIV-associated Kaposi sarcoma. F1000Res. 2019;8. doi:10.12688/f1000research.17401.1
  5. 5.
    June C, Sadelain M. Chimeric Antigen Receptor Therapy. N Engl J Med. 2018;379(1):64-73. doi:10.1056/NEJMra1706169
  6. 6.
    Lee D, Santomasso B, Locke F, et al. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 2019;25(4):625-638. doi:10.1016/j.bbmt.2018.12.758
  7. 7.
    Alvarnas J, Zaia J, Forman S. How I treat patients with HIV-related hematological malignancies using hematopoietic cell transplantation. Blood. 2017;130(18):1976-1984. doi:10.1182/blood-2017-04-551606
  8. 8.
    Mulanovich V, Desai P, Popat U. Allogeneic stem cell transplantation for HIV-positive patients with hematologic malignancies. AIDS. 2016;30(17):2653-2657. doi:10.1097/QAD.0000000000001240
  9. 9.
    Hoffmann C, Sabranski M, Esser S. HIV-Associated Kaposi’s Sarcoma. Oncol Res Treat. 2017;40(3):94-98. doi:10.1159/000455971