Before we dive into the new HIV immunotherapy, let’s rewind a little – The treatment for HIV has come a long way since we first discovered the virus. Thanks to great leaps and strides made in the field, we have managed to assembled a regime known as Highly Active Antiretroviral Treatment (HAART), which has allowed patients with the condition to lead a near-normal life (get married, have kids, get employed) and live up near to their life expectancy – we have managed to turn what used to be a death-sentence or an isolation punishment, into near normal life experience.
That said, the current treatment, despite being able to produce undetectable level of viral load, has its own caveat. For one, you have to take the combination of two or three medications for the rest of your life, without failure, and just like any other thing in the planet, medication isn’t without its side effects. Reason number 2 (which explains reason reason number 1) the reason why patients have to take HAART for the rest of their life is because despite the ability of pre-existing drugs (prevent viral entry into the cells, prevent viral integration into human DNA and kill off HIV viruses in the blood) we have yet been able to kill off long, latent HIV virus that resides within the immune cells, thus having to take the medication throughout a patient’s lifetime.
That is until recently, a promising breakthrough on a new HIV immunotherapy has been made that was published in the journal EBioMedicine, earlier this month. The group of researchers from the University of Pittsburgh managed to develop a new HIV immunotherapy that doesn’t only force out the virus from hiding, but also permanently kill it – an all in one treatment for HIV. Although this study has yet to make in to the phase of human trial, this development could very well lead to the first creation of an HIV vaccine.
So, How Did They Managed To Develop The New HIV Immunotherapy?
“A lot of scientists are trying to develop a cure for HIV, and it’s usually built around the ‘kick and kill’ concept – kick the virus out of hiding and then kill it,” said senior author Robbie Mailliard, Ph.D., assistant professor of infectious diseases and microbiology at Pitt Public Health. “There are some promising therapies being developed for the kill, but the Holy Grail is figuring out which cells are harboring HIV so we know what to kick.”
The ‘kicking’ is needed because so long as the person continue to take the current HAART regime, the virus goes into a latent, inactive phase where it incorporates itself into the DNA of certain immune cells called T helper cells. So, the team decided to look at a different virus that also goes latent and infects more than half of adults – and 95 percent of those with HIV: Cytomegalovirus (CMV), which can cause eye infections and other serious illnesses, but is usually controlled by a healthy immune system.
The immune system spends a lot of time keeping CMV in check; in some people, 1 one out of every 5 T cells are specific to that one virus. This had the team thinking – maybe those cells that are specific to fighting CMV also make up a large part of the latent HIV reservoir? To test this hypothesis, they engineered an immunotherapy to not only target HIV, but to also activate CMV-specific T helper cells.
To run the experiment, the team needed a lot of blood and according to the first author, Jan Kristoff, they owe this success to the relentless cooperation of patients who sometime, had to be hooked up to a machine for four hours to have their blood analysed before coming back to give more and more samples. The core of this immunotherapy is immune cells called dendritic cells, which has been used in cancer immunotherapies and the conventional ones has also been used before this to induce the immune system to kill HIV. However, the ability to kick the virus out of hiding has yet to be an established feat for the dendritic cells. In this study, the team engineered “antigen-presenting type 1-polarized, monocyte-derived dendritic cells” (MDC1) that were primed in the lab to seek out and activate CMV-specific cells, with the thinking that they also may contain latent HIV.
When the MDC1 were added back to T helper cells containing latent HIV, they reversed that latency as expected, kicking the virus out of hiding and, the for the big moment, without adding any other drug or therapy, MDC1 were then able to recruit killer T cells to eliminate the virally infected cells. The team described it as the Swiss Army Knife of Immunotherapies.
The team now plans to start pursuing funding for clinical trials in humans — in the hopes of one day creating a vaccine that would allow HIV-infected people to stop taking their daily medications.
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