The need to improve access to cancer clinical trials of immune checkpoint inhibitors for people with HIV

Immune-based therapy

Cancer cells release chemical signals that can weaken the immune system and its ability to sense and attack tumours. For more than a decade, pharmaceutical companies have been developing a class of cancer treatments called immune checkpoint inhibitors. These drugs work by removing restraints (checkpoints) on the immune system that can become more common when tumours develop. In theory, removing these checkpoints should help to unleash the immune system’s natural ability to detect and attack tumours.

Examples of selected checkpoint inhibitors include the following:

  • Keytruda (pembrolizumab) – this affects a molecule called PD-1
  • Opdivo (nivolumab) – this affects a molecule called PD-1
  • Yervoy (ipilibumab) – this affects a molecule called CTLA-4

In some clinical trials of people without HIV who have cancer, checkpoint inhibitors have produced remarkable anti-cancer effects. However, many industry-sponsored trials have generally excluded people with HIV from large cancer clinical trials. Indeed, an analysis done by cancer specialists at Harvard University found that of “809 trials analyzed from 2019 to 2020, [nearly 75%] excluded […] people with HIV.” The Harvard researchers stated: “Despite increasing evidence for safe and effective immune checkpoint inhibitor use for people with HIV, most cancer immune checkpoint inhibitor trials exclude people with HIV and few studies permit [such people] to participate, even if HIV is well controlled.”

A small study done by researchers at the U.S. National Cancer Institute (NCI) focused on 87 designs for clinical trials (protocols) that were planned between 2014 and 2020.  This study examined protocols that were planned for immune checkpoint inhibitors. The NCI study found that initially most protocols for the trials (84%) had no plans to recruit people with HIV who had cancer. But, after advocacy by the Cancer Therapy Evaluation Program of the NCI, protocols were changed and about 70% of the protocols then stated that people with HIV with cancer could enroll.

However, according to the same researchers at the NCI, the revised protocols then appeared to place barriers on the recruitment of people with HIV. The various barriers included having a minimum CD4+ count of 500 cells/mm3, not being allowed to use antibiotics to prevent any infections, and, in some cases, excluding anyone who had ever had an AIDS-related infection regardless of their current CD4+ count. Follow-up research is needed to assess how many people with HIV subsequently were able to enroll in clinical trials of immune checkpoint inhibitors in these modified protocols.

At any rate, readers can see why doctors do not have large databases from which they can draw firm conclusions about the effects of immune checkpoint inhibitors on the cancers of people with HIV.

To remedy this situation, it would be helpful if the pharmaceutical industry and research institutes could facilitate trials of immune checkpoint inhibitors in people with HIV who have cancer so that doctors can gain experience with these drugs in this population.

For the future

Since 1996, effective HIV treatment (ART) has been amazingly transformational in Canada and other high-income countries. ART has turned an inevitably fatal viral infection into a chronic, manageable disease with a near-normal life expectancy for most people who take the medications as directed. If the life-prolonging effects of ART are to be fully realized, people with HIV who have cancer should have similar survival rates to people without HIV who have the same cancer. Perhaps equitable access to cancer therapy that works by harnessing the immune system is one possible approach to help people with HIV who have cancer and whose doctors judge such therapies to be needed.


Canadian Cancer Society

Cancer – Government of Canada

Cancer – Government of Quebec

Second cancer risk after surviving Hodgkin’s lymphoma in people with HIVCATIE News

French researchers investigate second cancers in people with HIV who survived a first cancerCATIE News

—Sean R. Hosein


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