cryptochrome's Journal: DAPY rhymes with Happy

The most immediate treatment for HIV happens to belong in what may be regarded as the simplest and so far only partially effective block on HIV: drugs.

Drugs are chemical compounds which inhibit, enhance, or otherwise interfere with the biochemical processes involved in disease and its defense. Most of the time they are rather small and often completely unnatural. Drugs have long been the method of choice when the body's own systems go awry due to injury, poisoning, or genetic disease, allowing us to intelligently if inelegantly regulate our own biochemical processes with natural plant and fungal compounds or more modern and powerful synthetics. More recently the class of drugs known as antibiotics revolutionized medicine by allowing us to specifically interfere with the biochemical processes at work in infectious bacteria, which are rather different from those of our own. Bacterial infections used to be the greatest danger of pre-modern times, but now rarely cause great worry.

What drugs were not very good for were viruses, which make extensive use of our normal cellular machinery to propogate themselves and have few biochemical targets of opportunity, none of them common. But when HIV failed to yield to vaccines, drugs became our second focus. Modern drug cocktails have become quite effective at keeping the virus in check, but HIV has a pronounced tendency to evolve around them.

The latest salvo in the battle is a class of drugs known as DAPYs, the power of which is twofold. Firstly, they are designed to specifically inhibit reverse transcriptase, a viral enzyme which copies the viral blueprint into our own DNA. In other words, DAPYs prevent our cells from actually becoming infected (most of the other drugs interfere with the replication within the already infected cell). Secondly, it is much more difficult for reverse transcriptase to mutate resistance to these compounds because the DAPYs under consideration are flexible, like a key that can shape itself to fit the lock. Putting it all together means you have a single drug that works as well as or better than today's complicated five-drug cocktails, and it is easy to manufacture and apparently has no significant side effects as well.

So far three DAPYs are working their way through FDA testing, with the latest - R278474, also known as ripilvirine - being the most promising. Its creators are highly optimistic, even going so far as to call it a "magic bullet that stops AIDS in its tracks." But is it a cure? The answer is probably no. In order to completely cure someone of HIV, four things would need to happen simultaneously and complementarily:

1) New infections of cells must be prevented
2) Virions must be cleared from the body
3) Virion-producing actively infected cells must be eliminated, or otherwise permanently prevented from producing virions.
4) Latently infected cells must be activated, so that they may be eliminated as in (3), or otherwise permanently prevented from producing virions.

DAPYs only prevent new infections (1). The immune system and time can handle (2) through humoral immunity and (3) through cellular and humoral immunity and cell death. But (4) is the kicker. Studies indicate HIV could stay hidden inside cells for up to 60 years. During that whole period of time, latent infections could be spontaneously activating and attempting to re-establish an acute infection - which would be largely undetectable like HIV infections now. Even if DAPYs work perfectly and no resistance was ever evolved to them, you'd have to consistently take them for the rest of your life in order to prevent you from becoming infectious again.

So although DAPYs might offer a way for people to avoid developing AIDS entirely, it is no cure for the underlying HIV infection. And if people no longer take AIDS seriously because totally effective treatments are available, they will likely stop taking precautions and undiagnosed infections will spread like wildfire through the population. All well and good if your infection is identified and you don't mind taking drugs for the rest of your life... and assuming HIV doesn't evolve resistance to DAPYs. We'd probably be better off putting it in the water before then.

There is some hope. The mechanisms by which HIV becomes latent, and the means to pull infected cells out of their latent state and thus flush out the viral reservoirs are being studied. But that research is far from yeilding any practical applications. And even if we did have them, how can we be sure the virus has been completely eliminated? In the meantime, DAPYs will be proving themselves in the real world within the next few years.