Medical intervention and the natural course of evolution may be dealing a double blow to the
The findings offer a kind of epidemiological and evolutionary checkup on the most deadly form of the virus, which has killed an estimated 39 million people after rapidly expanding in the human population in the 1980s.
The very fact that researchers can witness such evolutionary change may itself be a sobering testament to how long HIV has persisted, and how deeply it has settled in its new host population since first spilling over from monkeys in the early 1900s.
HIV's rapid acceleration since the 1980s appears to have had the effect predicted by virologists and by evolutionary theory: In a new host, a virus' capacity to cause disease and ultimately to kill its host diminishes over time.
The findings also suggest that thwarting HIV transmission by treating highly symptomatic patients with drug cocktails puts additional selective pressure on the virus and decreases its replication ability, according to the study published online this week in Proceedings of the National Academy of Sciences.
“HIV adaptation to the most effective immune responses we can make against it comes at a significant cost to its ability to replicate,” the study’s lead investigator, Dr. Philip Goulder, an immunologist at
These population-level results in the study won't directly affect the pursuit of a vaccine or other cure, per se, but they suggest that the target of such efforts has changed significantly over time.
Researchers compared data from Botswana and South Africa, where the AIDS epidemic has played out in different ways. The epidemic began earlier in Botswana, and the percentage of the population infected has been higher than in South Africa, which nonetheless has the greatest absolute number of HIV infections.
HIV won the molecular battle in humans in part by chance – mutations that help it evade human immune responses. These so-called escape mutants eventually dominate.
Such an adaptation has been evident in Japan, a country with one of the lowest HIV infection rates. There, strains of HIV impervious to an immune response among people with a certain gene variant (known as HLA-B*57) eventually constituted 75% of the HIV viral population. Studies also showed that viral replication capacity decreased during the same time span.
Researchers wanted to know whether the same effect could be seen in a comparison of epidemiological data between Botswana and South Africa.
They enrolled more than 2,000 women from both countries. In the Botswana sample, certain escape mutants were more dominant, and replication rates were lower, compared with South Africa, the study found.
By looking at two different groups of women in Botswana – one enrolled from 2002-2005, and another from 2012-2013, they found that the prevalence of six different escape mutants increased over a decade. Those results jibed with studies that showed gradual accumulation of certain escape mutants over a 20-year period in Amsterdam.
Researchers next tried to test the effects of antiretroviral therapy on the virus. Those therapies have been aimed at people whose white blood cells (CD4) decline rapidly – a response to HIV with high replication capacity. They created a mathematical model that showed this selective treatment slightly accelerates the evolution of HIV variants with a lower replication capacity.
There are many caveats in the study, not the least of which is that even an evolved HIV remains deadly. And the effects of antiretroviral therapies were modeled, not measured. The study also looked at a relatively narrow set of gene variants that affect AIDS progression.
Nonetheless, Goulder noted, "Anything we can do to increase the pressure on HIV … may allow scientists to reduce the destructive power of HIV over time."