May 02 2013

HIV Cure Close?

Only two patients have ever been demonstrably cured of HIV, the virus that causes AIDS. Timothy Brown has not had any detectable virus in his blood since receiving a bone-marrow transplant for leukemia. More recently a child infected with HIV at birth was apparently cured after receiving an early high-dose regimen of anti-retrovirals. These cases are considered “functional cures” – they have no detectable virus even off anti-retroviral medication.

The press has a habit of throwing around the word “cure” prematurely or inappropriately. We hear all the time about a potential “cure” for cancer, for example. Invariably the new treatment in question, if it pans out at all, becomes a useful treatment for cancer – one more tool in our toolbox – but not an outright cure.

I was therefore skeptical of the following headline, “HIV cure months away, Danish scientists say, citing novel new DNA treatment.” Perhaps there are Danish scientists claiming this, but that is a bold claim. I also worry about any clinical claim that a treatment is close. What does that mean, exactly? Either there is compelling clinical evidence of efficacy or there isn’t. You can’t predict the results of future research, so if the evidence isn’t here yet then we simply don’t know. At best such statements are expressing an optimistic hope.

Until the evidence is in, peer-reviewed, and published I can’t really say anything about its validity. The underlying concept, however, is interesting. Preliminary reports indicate that the scientists are working on a treatment that flushes the virus from its reservoirs in human DNA. If true, this sounds like a viable approach.

Part of the reason it is so difficult to completely eradicate HIV once an infection is established is that the virus hides out in reservoirs, hidden away from both anti-retroviral drugs and from the immune system. These reservoirs act as a continuing source of virus, so even when the virus is undetectable in the blood, it can still come back. HIV is therefore a chronic illness that need ongoing treatment, and not something that can be cured.

Another aspect of HIV that makes it difficult to fight is the fact that it is highly variable. In fact the virus tends to evolve within an infected individual. It is constantly eluding the immune system, therefore. This also makes it very difficult to create a vaccine to prevent infection.

Also, the entire strategy of the virus is to launch a preemptive strike against the host’s immune system., taking out the CD4 cells. This is what causes AIDS and the opportunistic infections and cancers that reduce life expectancy in HIV patients. Fortunately, the latest treatments reduce the viral load to the point that the immune system is not compromised. Patients can live chronically with HIV without developing AIDS.

But curing the HIV, or at least preventing its spread, has proven very difficult.

If there is a way to eradicate HIV from an infected individual, flushing the virus from its reservoirs sounds like the way to do it. So at the very least the approach sounds plausible.

It should also be noted that these Danish researchers are not the only ones to come up with this idea and to be working on this strategy. The idea here is to activate latent HIV reservoirs so that they can be targeted by anti-retroviral drugs. There are multiple research teams working on drug candidates for viral activation.

None, however, have proven efficacy in people. We seem to be getting close to this translational stage – going from candidate drugs that look promising in vitro to human trials.

The reports suggest that the Danes are at this same stage – they have a proof of concept, but not clinical data that demonstrates efficacy in people. This makes me suspicious that someone is just grabbing headlines by jumping the gun, edging out competing researchers without truly being any farther along in the research.

We will see. Perhaps they crossed a significant hurdle and moved us a step closer to human trials. It is all very encouraging. We now have very effective drugs to fight HIV, and have essentially turned it from a death sentence to a manageable chronic illness.

The next step is eradication, which will help reduce its spread. The primary hurdle for this is the latent reservoirs, and now researchers seem to be closing in on this problem as well. A “flush and destroy” approach seems likely to emerge eventually.

Regardless of which researchers cross the finish line first, this is a great victory for science. In one generation we have gone from the discovery of a new frightening infectious illness, to figuring out the viral cause and working out its entire life-cycle, and designing targeted treatments that improved to the point that we are now able to essentially put the infection into remission. We are still working on developing a vaccine, and now also on eradicating the virus entirely.

That is a dramatic success for reductionist science. Nothing in the “alternative” world can even come close. Science works. Everything else is just smoke and mirrors.

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