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HIV Patients with Cancer May Have a New Treatment Option

Although cancer is the leading killer of those with HIV, up until now these individuals have been unable to take advantage of the latest cancer treatments—such as immunotherapies—due to safety concerns. Results from Phase 1 of an ongoing clinical trial, however, reveal that cutting-edge cancer treatment may now, indeed, be a safe and effective option for this population.

Scientists at the National Cancer Institute’s HIV & AIDS Malignancy Branch recently released results from a study of pembrolizumab, a type of immunotherapy known as a checkpoint inhibitor. Checkpoint inhibitors prevent cancer cells from interfering with the body’s immune response and enable the immune system to correctly target these cells for destruction. The checkpoint protein known as PD-1, which exists on immune cells called T cells, is of particular interest to HIV researchers, as is a protein called PD-L1, found on both normal cells and cancer cells. When these two proteins unite and bring together a T cell and another cell, they send a signal for the T cell to leave the second cell alone—a good thing if the second cell is a normal cell, but less than optimal if the second cell is a cancer cell. Pembrolizumab works on PD-1 in order to stop it from binding with PD-L1, thus allowing T cells to destroy the cancer cells they encounter without any obstruction.

The first 17 patients in this study, known as CITN-12, were already on antiretroviral therapy and displayed generally good responses to pembrolizumab. This information opens the door to cancer treatments that previously have been unavailable to those with HIV.

“The primary objective of CITN-12 is to evaluate safety in people with HIV across a range of CD4 counts,” Thomas Uldrick, MD, the study’s principal investigator, told Contagion ®. “To date, safety seems comparable to that described for HIV-uninfected patients with cancer. Often, for patients with HIV and advanced relapsed and refractory cancers, there are no other good treatment options. For patients with HIV and cancers for which anti-PD-1 or anti-PDL1 therapy is indicated, pembrolizumab and similar medications should be considered. For cancers for which PD-1 therapy is not approved, treatment on a clinical trial is advised.”

Why have HIV patients traditionally been excluded from studies involving cancer drugs? “This is in part due to poor outcomes in patients with HIV and cancer prior to effective antiretroviral therapy,” Dr. Uldrick explained. “With 20-plus years of effective HIV therapy, this practice requires reevaluation. Sometimes exclusion is appropriate in patients with advanced HIV disease; other times it is overly cautious. When it comes to immunotherapy with anti-PD-1 therapy, it is known that people with HIV, even when well controlled, can have some degree of measurable immune dysfunction of unknown clinical significance. For this reason, specifically evaluating anti-PD-1 therapy in people with HIV is particularly important.”

According to Dr. Uldrick, about a third of cancers in the United States are AIDS-defining ones—cervical cancer, Kaposi sarcoma, and non-Hodgkin lymphoma—with the rest affecting areas such as the breast, lung, liver, head, and neck. “With the aging of the population with HIV, the shift to other cancers is expected to continue,” he said.

CITN-12, which is ongoing at 8 different sites, will enroll as many as 36 patients. Going forward, scientists plan to study pembrolizumab as a potential therapy for patients who have HIV and Kaposi sarcoma, as the drug’s effect on this population has not yet been scrutinized. Kaposi sarcoma, characterized by skin lesions, is particularly common in sub-Saharan Africa, where HIV proliferates.
Laurie Saloman, MS, is a health writer with more than 20 years of experience working for both consumer- and physician-focused publications. She is a graduate of Brandeis University and the Medill School of Journalism at Northwestern University. She lives in New Jersey with her family.
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