New HIV Weapon: A Cancer Drug That Kills HIV-Infected Cells

A drug originally meant to treating cancer seems to have another unexpected but equally amazing potential, that of treating HIV.

JQ1, named after chemist and research scientist Jun Qi, is already in early stages of human trials as a cancer drug. The anti-cancer medicine can also treat heart failure and inflammation, and is also touted as a male contraceptive. It should be noted that JQ1’s unexpected property as a possible tool against HIV by reactivating or waking up latent HIV in the body has been known since 2012.

But wait…reactivating?!! Aren’t drugs supposed to stop diseases?

While the approach appears a bit contradictory, reactivating HIV is one of the modern strategies in finding a cure for the dreaded disease.

HIV (human immunodeficiency virus) infects human and weakens the immune system to the point where the body cannot defend itself anymore against infections that aren’t plaguing healthy persons. The virus destroys CD4+ T cells, white blood cells that are an integral part of our immune system. When the body’s CD4 count goes below 200 cells/mL (normal range is 500 to 1500), HIV reaches an advanced condition which is referred to as AIDS (acquired immune deficiency syndrome).

According to UNAIDS.org:

• In 2016, there were 36.7 million PLHIV (people living with HIV). Out of these, 19.5 million were on antiretroviral therapy (ART). 1 million have died due to AIDS-related illnesses.
• Since the start of the epidemic, 76.1 million people have been infected with HIV. Out of these, 35.1 million have already died.

ART is the current and only effective weapon of PLHIV against the virus. The therapy usually is made from three different anti-HIV drugs; three or more drugs are necessary to prevent resistance as HIV is notorious for its rapid mutations. While ART has been effective in controlling HIV from multiplying and allowing PLHIV lead normal lives, it is not a cure and can only kill the active viruses found circulating within the body. That’s the drugs must be taken non-stop to prevent reactivation of sleeping (latent or dormant) viruses that are hidden in “reservoir cells”.

Scientists have been probing for a functional cure for years. Some recent breakthroughs involve vaccines, stem cell transplant and gene therapy. The reactivation process of HIV plays a role in “shock-and-kill” and “silencing” strategies, two of the most viable approaches undertaken by HIV researchers.

Researchers from Gladstone Institutes, a research facility based in California, were testing the drug JQ1 on cancer patients but they were frustrated with the inconsistent results. JQ1 halts the activity of a cancer-linked protein called BDR4, however, they realized that the drug also stops a shorter form of this protein. A short BDR4 acts in an ART-like manner as it is also a co-repressor of HIV growth.

Going back to the reactivation part of the disease, JQ1 stops short BDR4 variants and the interaction “shocks” latent viruses to go out and be “killed” by antiretroviral drugs. At the same time, the resurfacing must be slow so that the body’s immune system, if strong enough, can also do its part to “silence” the viruses for good.  Both the “shock-and-kill” and “silencing” approach may potentially allow PLHIV in the future to stop taking their anti-HIV drugs.

“Silencing and reactivating HIV are often seen as competing approaches, but I think they could actually be combined to develop more effective therapies in the future,” said Melanie Ott, senior Gladstone investigator and a professor of University of California, San Francisco. “You could start by shocking and killing the virus that’s easy to target, then use silencing mechanisms to slow the resurfacing of latent virus.”

While the team’s findings are still experimental, the study is certainly a step forward in the fight of finding the elusive cure for HIV.

The study was published in Molecular Cell.

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