Treatment of HIV Associated Cancer

Executive Summary

Treatment recommendations depend upon the size, grade and type of tumor, metastasis, possible side effects, and patient’s (HIV Associated Cancer) preferences and overall health. The common treatment for HIV associated cancer include surgery, radiation and cytotoxic chemotherapy, immunotherapy and stem cell transplantation. HIV/AIDS cancer treatment options have also evolved from multiple daily doses, ineffective regimes, and drugs with severe side effects to single daily tablets with minimal toxicity and medications with fewer side effects that can completely suppress the circulating virus. Other treatment approaches include traditional cancer therapy, chemotherapy, cancer immunotherapy (checkpoint inhibitors, chimeric antigen receptor T-cell therapy), and stem cell transplantation (Autologous and allogeneic SCT).

Treatment of HIV Associated Cancer

HIV positive patients have a higher risk of getting cancer than the general population. Although this risk appears to be higher for malignancies resulting from co-infection with viruses and bacteria, HIV-positive individuals also have a higher risk of infection-unrelated malignancies. The risk of cancer during HIV infection is a complex interplay between traditional risk factors, prolonged life expectancy, co-infection with pro-oncogenic viruses, possible direct carcinogenic effects of HIV, cART toxicity, coagulation and activated inflammation^​1​. Cancer mortality in people with HIV associated cancer may be the result of many factors, such as HIV-associated immunosuppression, hindrances in access to care, early diagnosis, and complications associated with HIV and cancer treatment.

Oncologists unfamiliar with cancer treatment among PLWH may be concerned about the safety of cancer treatment in this complex population. Due to this, unfortunately, some PLWH do not receive any cancer treatments leading to increased cancer mortality. Aging, low CD4+ T cell counts in PLWH, intravenous drug use as a mode of HIV transmission, and metastatic disease are associated with a lack of cancer treatment. These extend to all cancer stages as well as multiple cancer treatment modalities, including surgery, chemotherapy, and radiation^​2​.

The National Comprehensive Cancer Network has suggested guidelines for the preparation of treatment regime of patients with HIV and cancer^​3​.

• Screen all patients with cancer routinely for HIV.
• Establish collaboration between oncology team(s) and HIV providers.
• Linkage to HIV care will lead to prompt initiation of an HIV regimen; with the understanding of oncologic treatment based on collaboration, ART regime will have goals to minimize adverse effects and drug-drug interactions.
• Cancer treatment should not be delayed for HIV workup and management.
• ART should be offered promptly, but some suggest ≥7 days prior to cancer treatment or after cancer treatment has been started to differentiate issues of tolerance to therapy.
• Avoid interruption in HIV/AIDS cancer treatment due to concerns for opportunistic infection, worse outcomes of cancer treatment, lower survival.

Cancer treatment has evolved, from surgery to radiation and cytotoxic chemotherapy to immunotherapy and stem cell transplantation. HIV/AIDS cancer treatment options have also evolved from multiple daily doses, ineffective regimes, drugs with severe side effects to single daily tablets with minimal toxicity and medications with fewer side effects that can completely suppress the circulating virus. These greatly improved HIV/AIDS cancer treatment options and have increased the willingness of oncologists to treat HIV infected cancer patients.

The various regimes for treatment of HIV/AIDS cancers are as follows

Traditional cancer therapy

The provision of surgery, chemotherapy and radiation has been shown to be safe for HIV-positive patients with a variety of cancers, with monitoring of liver ailment or kidney disease, the risk for esophageal and other gastrointestinal toxicity arising from the use of chemotherapy or radiation which can hinder the tolerance or absorption of ART as well as bone marrow suppression. Current HIV treatment is greatly simplified with multiple single-tablet daily regimens and fewer drug-drug interactions than ever before. NCCN recently published guidelines for the treatment of patients with cancer and HIV elucidates the importance of cancer treatment proceedings without delay while working with HIV providers to evaluate risk of opportunistic infections and drug-drug interactions.

Chemotherapy

Chemotherapy is the method of cancer treatment using drugs that prevent the cancer cells from growing by killing them or arresting their growth. When chemotherapy is given orally or injected into a muscle or vein, the chemotherapeutic drug can reach the sites of cancer cells throughout the body via the bloodstream (systemic chemotherapy). When chemotherapy is given directly into the cerebrospinal fluid (intrathecal chemotherapy) or to any organ or body cavity, such as the abdomen, the chemotherapeutic drugs primarily affect cancer cells in these localized areas (regional chemotherapy). AIDS-related peripheral/systemic lymphoma can also be treated with chemotherapeutic drugs. Many a time, doctors also prescribe the use of high activity antiretroviral therapy (HAART) during or after chemotherapy for getting the best outcome. Chemotherapeutic drugs may include Nucleoside reverse transcriptase inhibitors, Non nucleoside reverse transcriptase inhibitors, Protease inhibitors, Integrase strand transfer inhibitors and Attachment inhibitors.

Radiation therapy

Radiation therapy for cancer treatment uses high-energy radiation or X-rays to kill or arrest the growth of cancer cells. In the case of external radiation therapy, a machine placed outside the body of the patient is used to emit high energy radiation to the region of the body with cancer cells or tumours.

Cancer Immunotherapy

Checkpoint inhibitors

Immune checkpoints are largely used in cancer immunotherapy which helps in reducing the “collateral” damage arising from an uncontrolled immune response that leads to autoimmune destruction of organs and tissues. The underlying vital role of the immune response, along with the chronic viral infections and cancer findings, can lead to the overexpression of these molecules, which can approach to inhibit these constraints on the immune system. These immune checkpoint inhibitors (ICIs) consist predominantly of programmed cell death-1 (PD-1), cytotoxic T-lymphocyte antigen-4 (CTLA-4), and programmed cell death ligand-1 (PD-L1) inhibitors. The first FDA approved for the treatment of cancer with ICIs was the anti-CTLA-4 agent ipilimumab, approved for melanoma treatment in 2011. Studies have indicated that immunotherapy treatments against cancer could reduce the viral load among HIV infected patients, thus elucidating that cancer immunotherapy can fight HIV too^​4,5​.

Chimeric antigen receptor T-cell therapy

Genetically modified autologous or allogeneic CAR T-cells displaying specific activity against cancerous cells often exhibit a highly toxic but efficient approach for cancer therapy. The most common toxicities are CAR T cell-associated encephalopathy syndrome and cytokine release syndrome, which may often be present concurrently, thus making it difficult to differentiate from infection. Clinical trials are underway to develop CAR T cell therapy for the treatment of HIV, specifically to prevent the spread of cancer among HIV infected individuals^​4​.

Stem Cell Transplantation

Autologous and allogeneic SCT has been used successfully to treat HIV patients, providing a well-tolerated daily treatment option displaying fewer drug-drug interactions and side effects that may serve as an alternative for the treatment of cancer patients who have developed renal or hepatotoxicity. The initial total white blood cell count and the CD4 count may be low during SCT based cancer treatment, and recovery may take up to a year. There may also be a temporary increase in viral load, but there are usually no associated complications. Although the use of Allogeneic SCT in HIV patients has not been reported adequately, but few studies have reported that it is possible and safe in some cancer patients with well-controlled HIV^​4​.

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