The Promise and Risk of ‘Flushing’ Treatments
Guest writer Jim Fox on research in to eradicating HIV from those reservoirs in our bodies where the virus hides
Recent advances in a number of research fields, particularly the antiretrovirals (ARVs) have largely transformed HIV/AIDS from a painful death sentence to a manageable illness. And additional advances in peripheral fields like gene therapy, vaccines, cellular manipulation, etc., actually have immunologists and researches using the word “cure” without fear of being tagged as irresponsible pipe-dreamers. However, so far the hypothetical end-product of most of these research paths have been qualified as “functional cures”.
A functional cure is generally defined as one in which the virus has been beaten into harmless remission and remains there without the need for adhering to an expensive drug regimen.
While remission and freedom from reliance on the cocktail is nothing to turn one’s nose up at, even the most effective treatments leave concentrations of the HIV virus lingering in the body. These viral “reservoirs” (or “latent reservoirs”) are problematic chiefly because in most HIV-positive people, when drug therapy stops, those reservoirs soon flood the body and the immune system is once again attacked. To affect an actual cure, the viral reservoirs in the brain/central nervous system, gut and other common retreats for dormant HIV must be flushed out where it can be killed by ARVs. If not, relapse is a near certainty. Researchers are working to find flushing agents on several fronts. Here are some of the most promising:
HAART. Dr. David Ho is probably one of the two biggest names in HIV research; the other being Dr. Robert Gallo. 1996 Time Man of the Year Ho has dedicated a considerable portion of his career to highly active retroviral therapy (HAART). HAART treatments block the action of reverse transcriptase and protease - two enzymes necessary to HIV’s replication and cell infiltration. Ho believes that if a patient strictly abides by their HAART drug regime even the viruses hiding in the latent reservoirs could be disabled and eliminated in roughly six years.
Drawbacks. As is the case with any powerful drugs, the HAART cocktail’s side effects can be rough and even dangerous. Plus, a sizable chunk of those committed to HIV research insist that no drug therapy can eradicate the virus entirely.
HDAC Inhibitors or HDIs. Histone deacetylase inhibitors (HDACs or HDIs) have long been used as mood-stabilizers and anti-epileptics and more recently have proved promising for battling cancer. Within the past few years, however, they’ve come to the attention of immuno-virologist specialists for their apparent efficiency at highlighting and purging dormant HIV from the cells concealing them. The two being most actively investigated are vorinostat and valproic acid.
Drawbacks. Once again, while the results emerging from very small-scale clinical trials has been promising, use of HDIs in the fight against HIV is new and they may prove prohibitively toxic. Aforementioned HIV pioneer Dr. Robert Gallo (among others) further warns that there is no 100% guarantee that all of the flushed virus will be dead or killed. If the HDIs don’t work as is hoped, they could actually contribute to the establishment of more entrenched latent reservoirs in the brain.
Disulfiram. In another strange case of drugs better known for their use in the treatment of unrelated, psychiatric/neurological disorders (and perhaps cancer), the drug disulfiram is both better known as Antabuse and for its use in the treatment of chronic alcoholism by creating an acute sensitivity to alcohol. In the lab and limited clinical trials, though, disulfiram did exhibit potential as a reservoir-draining latent HIV activator.
Drawbacks. Over the long term, disulfiram trials saw a reservoir-depletion of around 14%; which is statistically insignificant. However, researchers found that it was efficacious in short-term latent viral activation and was well tolerated, meaning it could be incorporated into a broader treatment strategy. The most troubling drawback, of course, is that one couldn’t drink during disulfiram treatment!
Prostratin and DPP. Prostratin and its chemical cousin DPP are poignant arguments for the preservation and study of forests and traditional medicinal practices around the world. They are chemicals initially derived from the bark of the Somoan mamala tree, a resource locals have been using to battle blood disorders for years. Early research into prostratin and DPP’s viability as a latent HIV activator and reservoir-depletion mechanism has been encouraging.
Drawbacks. Synthesizing prostratin and DPP have proved difficult considering the rarity of their source material and relative newness of their appearance. That newness is another drawback as possible side-effects, long-term repercussions and long-term effectiveness are not well known.
As hopeful as the prognosis is for any or all of these treatments, virtually all scientists point out that this sort of research is in its relative infancy. It’s also a branch of HIV-eradication medicine that is something of an all-or-nothing proposition. Even an effectiveness of 95% is five percent too little.
Guest writer Jim Fox is a freelance writer who studied medicine for his undergraduate degree. He frequently writes about topics pertaining to the medical industry, including affordable RX drugs. When he isn't typing the day away, Jim is either perfecting his wine recipes or lacing up his ice skates and heading for the nearest frozen water.