A drug used to treat lung cancer has led to a ‘drastic and persistent decrease’ of HIV-infected cells in a French patient.
Treatment with the PD-1 inhibitor nivolumab led to a sustained reduction in the HIV reservoirs in the patient, according to the French researchers.
“In this patient we observed, as expected, both a re-activation of HIV and an increase in CD8 T cell responses against HIV, which resulted in the drastic decrease in the HIV reservoir, thus leading to a sustained reduction of the HIV reservoirs,” said lead author Professor Spano, head of the medical oncology department at Pitie-Salpetriere Hospital AP-HP in Paris.
“This is the first demonstration of this mechanism working in humans. It could have implications for HIV patients, both with and without cancer, as it can work on HIV reservoirs and tumour cells independently. The absence of side effects in this patient is also good news, and suggests this could be an optimum treatment for HIV-infected patients with cancer.”
However the authors caution that the drug was not effective in another HIV-infected cancer patient, but say their results potentially suggest another avenue towards finding a cure.
Here’s what local experts had to say about the finding:
Clovis Palmer is Head of the HIV Immunometabolism and Inflammatory Laboratory at the Burnet Institute.
“This new data revive hopes that it is possible to reprogram immune cells in HIV-positive persons to fight the infection. Immune cells in these persons are what we call ‘exhausted’ – they are incapable of fighting HIV by themselves.
This work demonstrates that immune cell exhaustion can be reversed.
However, previous studies employing this drug (nivolumab) in HIV-positive showed less impressive results or no effects at all. Therefore, at best, this type of treatment will have to be personalised, and in the context of HIV cure that means many, often poor and vulnerable communities will be left out of any benefits.
The team examined the HIV reservoir in immune cells from the blood. The major challenge toward an HIV cure is to eradicate the reservoir from sanctuary organs like the gut and brain where most of the hidden HIV resides. There is no evidence that this drug decreases the reservoir in these tissues.
Further, it is unknown whether first line cancer therapy given to this patient before nivolumab impacted the outcome of the reservoir size, and the clinical benefits since the patient did not interrupt their antiretroviral medication.
Notwithstanding, the results confirmed that it is possible to re-energise the immune system in HIV-positive persons.
But there are many challenging questions ahead: Can the energised immune cells seek out and kill reservoir cells in sanctuary organs? And what about viral rebound is HIV treatment is interrupted?”
Dr Mark Polizzotto is head of the Therapeutics and Vaccine Research Program at The Kirby Institute for Infection and Immunity in Society
“There is widespread interest in the possibility that cancer drugs acting on the immune system could also help eradicate HIV infection from the body.
Several studies, including two here in Australia, are evaluating this hypothesis in people with HIV and cancer who require these drugs for their cancer treatment.
This report of a single person with HIV and cancer offers encouragement that this approach has potential. However, as a single case it requires confirmation in larger studies.
It is also important to note that these cancer drugs have significant side-effects that make them less suitable for healthy people with HIV who do not require cancer treatment. The pathway to HIV eradication will require significant advances in our scientific understanding, and the development of safer drugs.
People living with HIV in Australia can be encouraged by the long term scientific interest in Australia and internationally in eradicating HIV.
These results are encouraging but preliminary, and ongoing studies in people with HIV and cancer, including one being conducted at the Kirby Institute, will be crucial.”
Prof Martyn French is an Emeritus Professor in the Faculty of Health and Medical Sciences at the University of Western Australia.
“This publication describes the effects of nivolumab therapy on HIV infection in a single patient with cancer who also had treated HIV infection. Nivolumab consists of synthetic antibodies that specifically block a protein (Programmed Cell Death Molecule-1 [PD-1]) that under normal circumstances is expressed by immune cells to regulate immune responses and prevent excessive inflammation.
Some types of cancer activate PD-1 inappropriately and suppress killer immune cells trying to kill the cancer cells. In addition, HIV infection increases PD-1 on killer T cells so that they become ‘exhausted’ and less effective at clearing the reservoirs of HIV-infected cells that persist in patients treated with antiretroviral therapy.
The patient in this report received nivolumab to treat aggressive lung cancer, but the investigators also showed that blocking the activity of the PD-1 protein also released HIV from reservoirs of persistent infection and enhanced the activity of killer T cells to decrease the number of HIV-infected cells.
The data presented are impressive and highly relevant to research on HIV cure strategies. However, the effects of this therapy were demonstrated in only one patient and the results of clinical trials on large groups of patients are needed before conclusions about the role of this type of therapy in curing HIV infection can be made.”
Associate Professor Sanjaya Senanayake is a specialist in Infectious Diseases and Associate Professor Of Medicine at The Australian National University
“Treating HIV infection has never been easier than it is today due to the variety of antiviral medications available; however, HIV still cannot be cured. Even people with no detectable HIV in the blood are still infected. This is because the virus hides in cells in places such as the brain, digestive system and blood system.
This reservoir of HIV-infected cells is called latent (or dormant) because the cells are not actively producing HIV. This lack of activity means that the immune system can’t find and destroy them. Therefore, being able to find and destroy this group of dormant infected cells could potentially lead to a cure of HIV.
In this paper, a drug used to treat cancer in a HIV-positive man appeared to “wake up” the sleeping or latent HIV-infected cells, allowing the immune system to identify and eliminate them.
While this is very exciting, the obvious limitation is that this is from a single case report, which means that it’s unclear if this result would be reproducible if given to other people with HIV. In other words, well-designed clinical trials would have to be carried out with large numbers of HIV patients to see if this drug is effective and doesn’t cause untoward side effects in HIV-positive people.
The other feature of this case worth highlighting is that a cancer drug appears to have an effect on an infection.
It is not uncommon for new medications, designed for one purpose (e.g. depression) to end up being used for another (e.g. as an antibiotic).”
These comments have been collated by the Science Media Centre.