Cancer drug could help HIV
Researchers have found evidence that a cancer drug may be able to eradicate HIV-infected cells in humans.
A team at Pitie-Salpetriere Hospital in France report that while treating an HIV-infected lung cancer patient with the cancer drug nivolumab, they observed a “drastic and persistent decrease” in the reservoirs of cells in the body where the human immunodeficiency virus (HIV) is able to hide away from attack by anti-retroviral therapy.
These reservoirs of HIV-infected cells are found in the immune system in organs such as the brain, bone marrow and genital tract.
They lie dormant and cannot be eliminated by anti-retroviral therapy, nor by the weakened immune system, so that if treatment is stopped at any time, the virus starts to replicate and infect more cells again, while the immune system cannot suppress this rebound of HIV infection.
If scientists could find a way of clearing away the reservoirs of HIV-infected cells, then it might enable them to eradicate the virus completely, making it possible to cure HIV patients.
HIV primarily infects CD4 T cells, which are a type of white blood cell that plays an important role in regulating the immune response. When under attack from HIV they not only become infected but also exhausted, meaning they are less able to fight the infection.
“Dormant CD4 T cells infected with HIV are not actively producing HIV: they are latently infected,” explains Professor Jean-Philippe Spano, head of the medical oncology department at the hospital.
“Latent HIV reservoirs are established during the earliest stage of HIV infection and throughout the course of the disease.
“When a latently infected cell is reactivated, the cell begins to produce HIV again. However, this re-activation is blocked in most latently-infected cells by cellular molecules called immune check-points.
“One of these check-points is programmed death-1 (PD-1), which also blocks the functions of CD4 T cells in fighting the virus.
“Increasingly, researchers have been looking into the use of certain drugs that appear to re-activate the latent HIV-infected cells. This could have the effect of making them visible to the immune system, which could then attack them.
“Drugs that inhibit immune check-points such as PD-1 are well known in the cancer field as being very efficient at restoring immune defences by removing the brake, enabling the immune cells to spring into action to reject the cancer cells.
“It was thought, but until now not demonstrated, that inhibitors of immune check-points could, in a similar way, wake up dormant HIV-infected cells and also the immune defences against the virus.”
The patient will be treated with more nivolumab later this month and his cancer will also be assessed then.
“For the moment, he is doing quite well and doesn’t show any signs of disease, even though the cancer is progressing slowly, which suggests it is not optimally controlled,” said Professor Spano.
The researchers are excited but cautious about their results.
“Firstly, this is the first case of such a drastic decrease of the HIV reservoir, and we must remain careful, especially because this is only one case; we have published details of another case where there was no decrease of the HIV reservoir,” Professor Spano said.
“Secondly, we have to evaluate – in clinical trials and in a group of fifty French patients we are treating currently – the potential toxicities of these drugs in HIV infected people.
“And finally, we have to identify markers that can predict HIV response to the anti-PD-1 therapy so that treatment can be personalised, especially as we observed one responder and one non-responder.”
Associate Professor Sanjaya Senanayake - a specialist in Infectious Diseases and Associate Professor Of Medicine at The Australian National University – says it could be an important step to the complete eradication of HIV.
“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,” he said.
“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.”
Dr Mark Polizzotto - head of the Therapeutics and Vaccine Research Program at The Kirby Institute for Infection and Immunity in Society – says it adds to a growing weight of scientific findings.
"There is widespread interest in the possibility that cancer drugs acting on the immune system could also help eradicate HIV infection from the body,” he said.
“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.”