fighting hiv with hiv-lite? maybe, maybe not.

Epidemiologists are thinking about trying to stop the spread of HIV with more HIV, but a strain engineered to be harmless to humans.
hiv virus 3d model

Humanity’s great scourges had a rough century after their victims finally armed themselves with germ theory, vaccines, and antibiotics. Smallpox was suppressed into extinction. Tuberculosis is tamed. The plague is no longer a death sentence. Cancer remains, but we are making strides against it and starting to figure out new ways to fight it. But as we’re treating the diseases of old, new killers are emerging. Ebola is a terrifying beast which has about the same effectiveness as acute radiation poisoning, and HIV is silently killing millions with its stealth attack on immune systems, triggering the onset of AIDS. Anti-retroviral drugs seem to keep HIV at bay but there is no cure for it, and its method of transmission triggered religious interference into the matter, interference which makes things much, much worse, leading to ever more infections. Meanwhile, quacks, cranks, and opportunists who deny that HIV and AIDS are related greatly contribute to the problem by selling their nostrums to the infected and demonizing the retroviral medication which can keep them alive as a plot to scam the sick. These combined efforts create entire groups of people who won’t seek treatment and keep on infecting others, either too ashamed or too scared to get medical help, or who think they really don’t need it.

But what if there was a way to prevent future infections without requiring any active care for those infected but unwilling or unable to get treatment? Well, there might be. One idea is to spread a harmless version of HIV, stripped of its pathogenic genes, into the wild to compete with the disease itself. It sounds odd, but it actually has a sound basis in biology. Generally, the most successful virus is the one that keeps its host alive as long as possible because it has more chances to reproduce and spread, leaving traces of its presence buried in the hosts’ genomes. Up to 8% of our DNA seems to have risen from viruses which inhabited our ancestors’ cells and happily churned out more copies of themselves. So should a harmless variant of HIV infest us, any wild strain of HIV trying to attack our immune system would basically find an “occupied” sign and have a very hard time getting enough of a foothold in our bodies. And in a competition between an engineered harmless strain and a debilitating one, the harmless virus should win. Given to just 1% of those infected this stripped- down version of HIV along with anti-retroviral drugs, it should drastically drop new infection rates and lower a population’s overall prevalence from nearly 30% to 6.5% in some of the world’s most ravaged areas over the next half century since this harmless virus will quickly get to people who’ll tend to come in contact with those spreading the disease most prolifically. In a more cheerful scenario, HIV prevalence could go down to just a percent or so within a decade. Or at least that’s what a mathematical model says on the subject.

However, a mathematical model is not exactly a population study, and when it comes to biology, statistics are not necessarily a very good predictor of what will happen. Organisms constantly mutate and come in contact with all sorts of external agents which can trigger new directions in their evolution. For viruses and bacteria it happens at what seems like warp speed to macro organisms like us, which is why we now have so-called superbugs and need to dial back on our use of antibiotics. Evolution is working against us here, and we’re helping the superbugs to get even stronger and more impervious to our treatments because we keep killing their competition, competition which may be less harmful to us and can starve the superbugs into extinction. And this may be why we’re seeing a proposal to basically fight fire with fire and allow evolution to get variants of a certain virus to fight each other for new hosts while rigging the contest to make sure that one with which our bodies don’t even have to cope will starve its opponent. The scientific name for this concept is TIP, which stands for therapeutic interfering particles, and it’s been tried before with live attenuated vaccines intended to generate antibodies as quickly and efficiently as possible in an at-risk population. But, as noted by the trio of experts behind the mathematical model mentioned earlier, the idea is not without its risks. Using a stripped down version of HIV means that it could pick up or re-evolve the very genes which made it dangerous and by then, it could be living in many more people than the original virus it was meant to replace, or it could turn into something even more potent since its mutations in the wild would be impossible to control.

According to the authors the odds of the defanged HIV strain turning back into its previous form are rather low since the two viruses would be too similar and have too few genes to smoothly re-integrate. But that doesn’t exactly rule out the idea of the TIP strain developing into something different and very potent on its own, and if that were to happen after it spreads far and wide by medical intervention, the result could be a swift, stealthy epidemic. Even worse, it would be an epidemic that we started and propagated, making this a huge mess a lot of doctors would like to avoid on ethical grounds. Even with animal models and lab trials, we’re not exactly going to be guaranteed that TIPs won’t backfire on us sometime in the future because while we can try to give their evolution a shove in the direction we want, we can’t steer it, and with every new population infected with a competitor to HIV, the idea of simply readjusting its genome will become less and less plausible due not only to the logistics involved in getting everyone re-infected by a harmless virus, but with the variety of its mutations over the years and decades. When you try to fight fire with fire, you may get burned in the process and we still have a long way to go before we can confidently exploit evolution for our gain. Though maybe a future advance in nanotechnology will let us build a TIP that never mutates and could fend off HIV or another virus, but that’s a discussion that could easily take up a post in its own right.

See: Metzger, et al. (2011). Autonomous Targeting of Infectious Spreaders Using Engineered Transmissible Therapies PLoS Computational Biology, 7 (3) DOI: 10.1371/journal.pcbi.1002015

# health // aids / evolution / genetic engineering / hiv


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