Inaugural Guidelines for Patients With HIV Aim to Expand Therapy Options

Gita Suneja, MD

The HIV status of a patient who is living with the infection and has been diagnosed with cancer may be a component of a diagnostic workup but should not be the sole determining factor in making decisions about treatment, according to the first set of National Comprehensive Cancer Network (NCCN) guidelines for this population.¹

The recommendations reflect that there are worse overall and cancer-specific survival outcomes seen in the HIV-infected population compared with the general population, in part because people living with HIV are less likely to receive cancer treatment compared with uninfected patients, said Gita Suneja, MD, during a presentation at the 2018 NCCN Annual Conference in March.²

Specific guidance in the HIV-infected population was not previously available, partly because persons living with HIV were previously excluded from cancer clinical trials, creating a knowledge gap.

Suneja, associate professor, Department of Radiation Oncology and Global Health, Duke University School of Medicine, noted that there is an urgent need for these guidelines. In a survey of 500 oncologists, 20% to 25% said that they would not offer standard cancer therapy to a person living with HIV, but most physicians would be more likely to offer therapy if they had an understanding of the adverse effects and prognosis.

The guidelines (version 1.2018) cover the management of 5 specific AIDS-defining and non—AIDS-defining cancers in persons with HIV: cervical cancer, anal cancer, lung cancer, Hodgkin lymphoma (HL), and AIDS-related Kaposi sarcoma (KS), for which there are separate guidelines. Each of these cancers is more prevalent in persons with HIV than in the general population, noted Suneja.

Factors that contribute to increased cancer risk in HIV-infected persons is co-infection with oncogenic viruses, such as human papilloma virus (HPV) and human herpes virus (HHV)-8, a higher prevalence of smoking in the HIV population, and aging, owing to effective antiretroviral therapy (ART) that has increased life expectancy of the HIV-infected population. “The number of AIDS-defining cancers is actually declining, and that’s due to better immune function with modern antiretroviral therapy, and the number of non— AIDS-defining cancers is rising,” Suneja said.

A unique consideration in HIV-infected patients is that in the cancer workup, imaging may reveal lymphadenopathy with a non-malignant etiology. In such a circumstance, a nodal biopsy should be considered to confirm cancer involvement, said Suneja. Similarly, lesions of the brain, bone, lung, spleen, liver, or gastrointestinal tract can be noncancerous, especially if the patient has a low CD4-positive T-cell count or a high viral load. Differential diagnoses can include progressive multifocal leukoencephalopathy; other malignancies, such as non-Hodgkin lymphoma in the case of brain lesions; infection or tenofavirrelated bone lesions; and opportunistic infection with lung lesions.

Performance is a key driver of cancer treatment decision-making. In HIV-infected persons, poor performance status may be from the HIV itself, cancer, or other causes. “It’s important to consider the reason for the poor performance status, and whether or not it’s reversible with appropriate treatment,” she said. “Treating HIV may improve a patient’s performance status such that they are eligible for cancer treatment.”

Non-AIDS-Defining Cancer

A consult with both an oncologist and an HIV pharmacist before initiating cancer therapy is recommended because of the possibility of drug— drug interactions, and co-management is critical. Suneja also noted that testing for CD4 T-cell count and viral load should be done more frequently to prevent potential interactions that could make ART less effective.Kaposi Sarcoma

Although the risk of AIDS-related KS has declined dramatically with ART, the risk is still increased by more than 250 times in people living with HIV. HHV-8 is the etiologic infection that underlies the development of KS. Individual KS lesions may be distinct clones that arise from persistent immunosuppression and HHV-8 infection. “That means that treating existing disease doesn’t necessarily prevent future KS lesions,” Suneja said.

In the guideline, management of KS is divided into limited cutaneous and advanced cutaneous disease. ART is the backbone of treatment in either case, according to the guideline, as reconstitution of immune function is very important for control of KS.

If disease is asymptomatic and cosmetically acceptable to the patient, ART alone is an appropriate treatment paradigm, said Suneja. If the lesion is symptomatic or cosmetically unacceptable, additional first-line management options include referral to a clinical trial, topical therapy, systemic therapy, intralesional chemotherapy, radiation therapy, and local excision. Continued ART is recommended if the disease stabilizes; with disease progression, another first-line treatment option can be tried.

For advanced cutaneous, oral, visceral, or nodal disease, the guidelines recommend checking for eligibility for a clinical trial or eligibility for systemic therapy with ART as first-line options. For patients not eligible for a clinical trial or for systemic therapy, ART plus radiotherapy is the recommended first-line treatment.

Glucocorticoids should be avoided if possible because iatrogenic immunosuppression can promote the development of KS. However, glucocorticoids may be necessary in patients with immune reconstitution inflammatory syndrome, in which KS worsens as the immune system is reconstituted. Suneja cautioned that KS can also be complicated by lymphedema as there is a greater risk for deep tissue infections in affected limbs.

Cervical Cancer

Because persistent HPV infection is more common in people living with HIV, the risk of cervical cancer is increased. Treatment of precancerous cervical lesions may be difficult because endocervical extension of precancerous lesions is more common in people living with HIV. Evaluation for synchronous vulvar or anal cancer is recommended with identification of cervical lesions. The NCCN panel recommends that people living with HIV be treated as per the NCCN guidelines for cervical cancer.

Anal Cancer

The risk of anal cancer is up to 19 times higher in the HIV-infected population. They are also at higher risk for anal squamous epithelial neoplasia, a precursor to invasive anal cancer. HIV-infected persons with anal cancer are recommended to receive the same treatment as those not infected with HIV, the guidelines state, but with more frequent posttreatment surveillance (anoscopy every 3 to 6 months for 3 years).

Lung Cancer

Lung cancer is the most common non—AIDSdefining cancer in people living with HIV. Screening should be performed as per NCCN guidelines for lung cancer screening, but examination of this recommendation is ongoing because of the increased risk of lung cancer in HIV-infected persons even after controlling for smoking, Suneja said. “For now, we don’t have any evidence to suggest that screening parameters should be different,” she said. Treatment per NCCN guidelines for non–small cell lung cancer is recommended.

Hodgkin Lymphoma

The risk of HL is 5 to 14 times higher in HIV-infected individuals than in the general population. The classic histology is associated with HIV; the mixed cellularity subtype is the most common. In the HIV population, almost 90% of cases of HL are associated with Epstein-Barr virus. Often, the presentation of HL is more advanced in persons with HIV, including B symptoms and bone marrow involvement. “It’s important to remember that B symptoms could also represent opportunistic infection, especially if CD4 counts are low,” Suneja said.

Supportive Care

Doxorubicin (Adriamycin), bleomycin, vinblastine, dacarbazine (ABVD) is the preferred regimen for the treatment of HL in persons living with HIV. Dose reductions may be required for prolonged severe neutropenia. Growth factors may also be required in the HIV population for patients with a low CD4-positive T-cell count and prolonged severe neutropenia. PET/CT-guided therapy may be difficult in HIV-infected persons because of the previously mentioned non-cancerous lesions often found on imaging. “It still is what we recommend but there are potential confounders to look for,” Suneja said. Autologous stem cell transplant has been found to be safe and effective for relapsed or recurrent HL in the HIV population. If the CD4-positive T-cell count is <200 cells /μL, prophylactic antibiotics for gram-negative bacteria and Pneumocystis jiroveci pneumonia should be considered.Supportive care in HIV-infected persons is critically important to ensure that treatment toxicity is minimized. A high index of suspicion and early testing for opportunistic infections are recommended. Vaccine recommendations include avoidance of live virus vaccines with a low CD4 count and consideration of the new recombinant zoster vaccine in those 50 years and older.

References

1. National Comprehensive Cancer Network. Cancer in patients living with HIV, version 1.2018. NCCN website. nccn.org/professionals/physician_gls/ default.aspx#age. Published February 27, 2018. Accessed May 1, 2018.
2. Suneja G. New NCCN guidelines: Cancer in people living with HIV. Presented at: NCCN 23rd Annual Conference; March 22-24, 2018; Orlando, FL.