The Search for the Cure Heats Up! Part Three
Cure Strategies; Cure Realities
By Bob Frascino, M.D.
March 1, 2011
As I mentioned in Part I of this three-part blog-a-thon, HIV is far more clever and cunning than any of us realized in the early days of the epidemic, when we all assumed that with the three Ts -- time, talent and treasure -- we could cure HIV in the not-too-distant future. Three decades later, despite billions of dollars and the best efforts of research scientists, HIV still has no cure and has prematurely snuffed out the lives of over 25,000,000 people.
So why don't we have a cure? At the July 1996 International AIDS Conference in Vancouver, scientific evidence was presented that definitively showed effective combination antiretroviral therapy, which included the recently developed protease inhibitors, could reduce HIV in the blood to undetectable levels. Many assumed we merely needed to administer ART for a period of time, perhaps three to five years, in order for the virus to burn itself out and thus for HIVers to be cured. Unfortunately that was not reality, because each time ART was stopped, the virus came roaring back, no matter how long the individual remained undetectable before interrupting ART.
The reason for the resurgence when ART was no longer on board is the same reason curing HIV has been so incredibly challenging: viral reservoirs. So what the heck are they? Let me try to explain. Viruses, such as HIV, are not self-sufficient organisms, like certain bacteria, parasites or other germy illness-causing invaders. A virus is, in essence, just a small package containing a tiny strand of genetic material called DNA. This DNA contains the genetic code for the virus itself. For HIV to cause infection it must find a host (like me, for instance), enter the host's cells (such as my immune system CD4 T cells), and deliver its DNA payload directly into the genetic core (the nucleus) of the host cell, which is where the host DNA is stored. OK so far? Good. Let's proceed.
DNA is basically a long-chain chemical code that carries the genetic information that allows an organism to operate. It basically instructs the body's machinery, advising it to make proteins and other elements the organism needs to survive and thrive. Each of the trillions of cells in a human body contains a complete copy of its unique DNA. Cool eh? Most cells only use a small portion of the DNA strand. A human DNA strand is nearly six feet long when stretched out. That's several inches taller than me!
And so what does this have to do with HIV reservoirs? Glad you asked! HIV is an unusual virus, because it contains an enzyme (protein) called integrase. Integrase astonishingly "integrates" the small thread of viral DNA directly into the host DNA. Yeah I know, it sounds very sci-fi, doesn't it? The viral DNA then maliciously hijacks a small piece of the host cell's machinery and turns it into a crazed viral Xerox machine. The infected cell begins cranking out new HIV particles with amazing speed and efficiency. Each replication travels through the bloodstream in search of new cells to infect, transforming them into new manic viral copy machines. Frightening, eh?
So what about antiretrovirals? Effective combination ART can shut the copy machines off, halting the mass replication of the virus. But they unfortunately cannot excise the viral DNA from the host cell. The cell remains infected. Some viruses, even nasty ones like hepatitis C, can be eradicated ("cured") if viral replication is effectively turned off for a long enough period of time. But not HIV! As you may have guessed by now, HIV cunningly infects certain cells of the immune system, which are very, very long-lived. These are a subset of so-called memory cells. These memory cells help the body respond quickly to infections it has experienced in the past. It's a nifty immune mechanism, but a small portion of these remarkable memory cells (maybe only one in a million) become dormant sleeper cells. These can remain "asleep" and quiescent for decades. The dormant memory cells that are infected with HIV constitute the "latent HIV reservoir."
When these infected sleeper cells are awakened by a stimulus or immune challenge, they, too, become crazy HIV replication machines, spitting out new infectious HIV particles. Sure, if ART is on board, it can shut off viral replication and the awakened cell will eventually die. But due to the long life of some of these dormant sleeper memory cells, HIVers must stay on ART for decades and decades, essentially a lifetime. This is the crux of why a cure for HIV has been so elusive.
Of course those frustrated with the slow scientific pace toward curing HIV could turn to only one of the dozens of instant HIV cures (for a hefty fee) that are readily available on the Internet. There are a wide variety to choose from. These bogus products claim to immediately cure HIV with a zap of electricity, whiff of ozone or secret mixture of herbs. (See my blog on this topic: "Hocus-Pocus: Quantum Quackery, aka Alternative Medicines for HIV/AIDS, A View From the Reality-Based Universe"). By the way, these same products also cure cancer, diabetes, hemorrhoids, halitosis and the heartbreak of psoriasis. So you really get quite a bang for your buck.
Returning to a reality-based universe, although we still can't eradicate HIV, we are indeed closing in on a cure from several different paths. The simplest and most direct strategy for eradicating the virus involves administering a treatment to the HIVer that would wake up all the infected cells in the latent HIV reservoir so that they would start producing virus. ART would shut down viral replication, and the cell would eventually die, as it would no longer be dormant (asleep). This proposed scenario was attempted most notably with interleukin-2 and with valproic acid.
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