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Potential New Way to Treat HIV Discovered

It goes without saying that rarely do we read reports about patients who through early treatment have been able to somehow acquire the ability to naturally control the HIV virus (human immunodeficiency virus). While a few cases have been documented since the 1990s, the most interesting one is that of Timothy Brown. Known as “The Berlin Patient,” Brown is thought to be the only individual cured of HIV after receiving a bone marrow transplant with HIV-resistant donor stem cells.

But a case like this, as mentioned, is an exception considering scientists are still having a hard time developing an effective treatment that will successfully accomplish the elimination of the virus from human cells. The current standard treatment for HIV is known as the standard regimen, or combined antiretroviral therapy (cART). Although widely effective in terms of reducing the viral load of an infected person to undetectable levels, based on stats the regimen does not work for about one in six people.

Furthermore, the term “undetectable” does not suggest the viral count is zero. The term simply means that the numerical expression of the quantity of virus in a given volume is reduced to levels virtually undetectable by laboratory tests. In other words, if a patient takes the antiretroviral drugs religiously, the viral load as a result will be maintained at undetectable levels and prevented from increasing uncontrollably. However, since we are not obviously talking about HIV’s much hoped ‘sterilizing cure’, instances of a viral load shooting up as a consequence of some residual virus present in the body can still occur. Once that happens, the patient is considered to be on a viral rebound. That basically means the HIV could start attacking the immune system thus causing harm to the body by prompting the progression of several stages of infection.

But while the search for the elusive HIV cure has been ongoing for years, lately, and to be exact since summer of 2012, researchers and scientists have been talking more and more about the possibility of a functional cure. To some extent, this can be accomplished now—with lifelong use of cART. However, the idea of a functional cure is that of a treatment capable of suppressing the virus without patients needing to remain on cART indefinitely.

And that brings us to The Scripps Research Institute (TSRI) in Florida, where scientists seem to have discovered a new way of treating HIV.  In a new study published this week, the TSRI team said they focused their analytical research toward didehydro-Cortistatin A (dCA), a compound used to suppress HIV replication in infected “reservoir” cells. In combination with cART, the dCA drug acts in what TSRI Associate Professor Susana Valente referred to as the “block-and-lock” mechanism.

Basically what this mechanism does is that after the antiretroviral drugs bring down a person’s viral load to undetectable levels, the dCA not only blocks HIV reactivation within infected cells but also the replenishment of other infected cells which stimulate HIV spread and growth. The dCA compound then locks HIV into dormancy thus reducing the likelihood of a viral rebound.

“No other anti-retroviral used in the clinic today is able to completely suppress viral production in infected cells in vivo,” commented Valente. “When combining this drug with the standard cocktail of anti-retrovirals used to suppress infection in humanized mouse models of HIV-1 infection, our study found a drastic reduction in virus RNA present—it is really the proof-of-concept for a ‘functional cure.’”

In TSRI’s laboratory, two groups of mice underwent one month course of treatment. One group was given only cART. As a result, HIV reactivation was suppressed for 7 days after the end of the regimen. Meanwhile, the second group which was given the cART-dCA combo had viral suppression that lasted for 19 days.

TSRI has a long history with dCA. The compound was based on another HIV-disrupting natural compound called Cortistatin A, which can be extracted from the marine sponge Corticum simplex. In 2008, TSRI Chemist Phil Baran was the first person to synthesize dCA. In 2015, TSRI announced that dCA as a candidate drug against HIV and that it had more potency than its natural counterpart.

Despite cART’s success in helping HIV patients lead normal and healthy lives, the regimen is certainly not a fully functional let alone a sterilizing cure for the disease. cART is a lifetime commitment, and missing doses could eventually lead to viral rebounds, drug resistance and other adverse effects. In addition, antiretroviral drugs have many side effects though the latest ones are far safer and more tolerable than earlier versions.

A timeframe for when dCA could actually be tested on humans was not given.

It should be noted that there are uncertainties in terms of dCA’s ability as a compound to lead to a permanent virus suppression, or if it’ll be effective after a viral rebound takes place. The TSRI team is already working to address these concerns by conducting additional experiments.

HIV harms the body to a certain point that the immune system is too weak to fight infections that are normally harmless to healthy individuals. The virus destroys white blood cells called CD4+ T cells; a high viral load is often associated with a low, unhealthy CD4 count. If HIV is left untreated, this could lead to an end-stage, fatal condition called AIDS (acquired immune deficiency syndrome).

In 2016, 36.7 million people worldwide are diagnosed with HIV; out of these, 19.5 million people are on ART. In the same year, one million have already died due to AIDS-related illnesses.

As for the dCA, and as already mentioned, there are no plans when it will proceed to human trials. But once the results are validated, this discovery is sure to give hope to millions of people living with this fearful disease.

The TSRI study can be found in the journal Cell Reports.