Preventing and Treating HIV-Related Cancers ​

December 1 is World AIDS Day, a time to reflect on the phenomenal progress that has been made in fighting this disease. Thanks to the development of antiretroviral therapy that suppresses the HIV virus, many people with HIV are living healthier, longer lives. But World AIDS Day is also reminder to all that the fight against HIV/AIDS is far from over.

In the U.S. today, approximately 1.2 million people are living with HIV. Of those, 14 percent don’t know it.¹ As of 2019, approximately 38 million people around the world were living with HIV/AIDS.² In the U.S., HIV disproportionately affects marginalized populations, including racial, ethnic, and sexual and gender minorities who already experience barriers to healthcare and disparities in health outcomes.¹

Since the beginning of the HIV/AIDS epidemic, when AIDS-associated Kaposi sarcoma cases first began to appear in clusters, the National Cancer Institute (NCI) has had a pivotal role in research that has led to a better understanding and treatment of HIV/AIDS and AIDS-associated cancers. Access to highly active antiretroviral therapy (HAART) has led to fewer cases of AIDS-associated Kaposi sarcoma in the U.S. But individuals receiving HAART remain at an increased risk for AIDS-associated cancers, including aggressive B-cell non-Hodgkin lymphoma, cervical cancer, Kaposi sarcoma, and certain non-AIDS-defining cancers.³

Compared to the general population, people living with HIV are 19 times more likely to be diagnosed with anal cancer, three times more likely to be diagnosed with liver cancer, two times more likely to be diagnosed with lung cancer, twice as likely to be diagnosed with oral cavity/pharynx cancer, and eight times more likely to be diagnosed with Hodgkin lymphoma.³ The risk of dying from cancer is also greater for people living with HIV.³

The AIDS Malignancy Consortium

For 25 years, the NCI-funded AIDS Malignancy Consortium (AMC) has spearheaded efforts aimed at the prevention and treatment of HIV-related cancers. AMC oversees a clinical trials network, conducting studies and testing novel therapeutics specifically in patients with cancer who have HIV infection. In addition to U.S. trial sites, the AMC network includes sites in Africa and Latin America. AMC research has strengthened international practice guidelines, including treatment for Kaposi sarcoma and lymphoma; advanced prevention and management of human papillomavirus (HPV)-associated cancers; and furthered the use of precision therapeutics and immunotherapy for people living with HIV who receive antiretroviral therapy.

In September 2020, Joseph A. Sparano, MD, began his term as principal investigator and chair of the AMC after serving as AMC vice-chair for 14 years. Dr. Sparano is the associate chair in the Department of Oncology at Montefiore Medical Center, a professor of medicine at the Albert Einstein College of Medicine, and the associate director for clinical research at the NCI-designated Albert Einstein Cancer Center. Dr. Sparano also serves as co-principal investigator of a Minority Underserved NCORP grant at Montefiore-Einstein and deputy chair of the ECOG-ACRIN cooperative group. To support the consortium and lead its clinical trial network, which currently comprises 42 sites, Montefiore Health System and the Albert Einstein College of Medicine recently received a five-year $111 million grant from the NCI.

Clinical Trial Participation

In a conversation with ACCCBuzz, Dr. Sparano highlighted AMC’s cancer control and prevention efforts, specifically in regard to HPV-associated cancers. “People living with HIV have high rates of HPV-associated cancers, including anal cancer, cervical cancer, and head and neck cancer,” says Dr. Sparano. “Our group is focused particularly on the anal-genital dysplasia and testing strategies to screen for cancer and reduce cancer risk.”

In the U.S., there are approximately 8,000 new cases of cancer diagnosed in people living with HIV each year—often in marginalized populations. Participating in cancer clinical trials can be challenging for HIV-positive patients. “Because of the variety of different cancers that occur in people living with HIV in the U.S., we need to use the approaches that are being used for rare cancers in order to reach the most patients,” explains Dr. Sparano in a recent video. “This systematic approach has led to great strides in pediatric oncology.”

To promote clinical trial participation among patients with HIV, one approach is to evaluate the effectiveness of newly approved treatments—such as immunotherapy—in this patient population. For example, Dr. Sparano describes the AMC095 study: “We’re testing immunotherapy with nivolumab or the combination of nivolumab and ipilimumab, two FDA-approved immunotherapy drugs approved for a wide variety of cancers. We’re testing these drugs in patients with HIV infection and cancer to determine the drugs' efficacy and safety, and we’re evaluating the effect of the drugs on the underlying HIV infection and patients’ immune status.”

Another clinical trials option is to follow the example set by the researchers of rare cancers—such as Kaposi’s sarcoma (KS) and KS not associated with HIV infection—to develop a portfolio of trials that test the effectiveness of drugs approved for other cancers that are believed to have promise for KS.

Another approach described by Dr. Sparano is to more effectively coordinate efforts with other NCI-sponsored clinical trial groups, such as ECOG-ACRIN, which is testing different treatment strategies for anal cancer, an HPV-associated malignancy that occurs more commonly in people living with HIV. One ECOG-ACRIN study (EA2165) of high-risk anal cancer patients is evaluating the effectiveness of immunotherapy in adjuvant setting vs. no treatment after chemo-radiation to see whether the use of a checkpoint inhibitor can help reduce the risk of recurrence. The other ECOG-ACRIN study (EA2182) of lower-risk anal cancer patients is comparing standard chemo-radiation treatment vs. low-dose chemo-radiation in the hope of seeing a reduction in side effects.

While the ECOG-ACRIN trials are being conducted in the general population, the AIDS Malignancy Consortium is asking similar questions in a study of HIV-positive patients. “What we’ve done in AMC is design a trial where we take the experimental arm of each trial—so adjuvant immunotherapy for the high-risk group and low-dose chemo-radiation for the low-risk group—and enroll patients with HIV infection and anal cancer in a separate trial sponsored by AMC (AMC110),” explains Dr. Sparano. “The idea here is that although the trials led by ECOG-ACRIN will ultimately determine the effectiveness of the approaches that are being tested, by having the separate trials for patients with HIV testing the same treatment, we’ll get a better sense of the effectiveness and safety of the drugs in an HIV-positive population. If one or both of the ECOG-ACRIN trials prove to be positive and establish a new standard of care in that setting, then we can say, okay, these advances also apply to people living with HIV who have these specific cancer types based on results from the AMC110 trial.”

Prevention is the focus of the currently enrolling AMC ANCHOR Study, which aims to find the best ways to prevent anal cancer in people living with HIV. In this video, Dr. Sparano explains the ANCHOR trial and the direction of AMC research during the next several years.

On World AIDS Day, it is important for providers at community cancer care programs to be aware of the AIDS Malignancy Consortium and its mission. “For people living with HIV who develop cancer, we need to take the same approach that has led to such great strides in pediatric cancer, referring patients to clinical trials whenever possible,” says Dr. Sparano. “The AIDS Malignancy Consortium includes a large network of centers in the U.S. that are performing a wide array of trials that may be appropriate for patients with HIV-associated cancers, such as Kaposi’s sarcoma and lymphoma.”

References

1. U.S. Department of Health & Human Services. HIV.gov. Data and Trends. U.S. Statistics: Fast Facts. https://www.hiv.gov/hiv-basics/overview/data-and-trends/statistics

2. U.S. Department of Health & Human Services. HIV.gov. Data and Trends: The global HIV epidemic. https://www.hiv.gov/hiv-basics/overview/data-and-trends/global-statistics

3. National Cancer Institute. HIV Infection and Cancer Risk. https://www.cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/hiv-fact-sheet