HIV is one of the best studied organisms in history, yet there is still much we have to learn about it. And one of the big unknowns is how the virus is changing as it spreads through the human population.
Research published this week suggests that it may be evolving to become less virulent. But how that will affect the progress of the HIV pandemic, or the number of people who will be killed by AIDS, remains almost impossible to say.
Kevin Ari毛n of the HIV and retroviral research unit at the Institute of Tropical Medicine in Antwerp, Belgium, and colleagues found evidence of diminishing virulence when they examined the HIV-1 Group M strain of the virus (see Chart). They compared samples of virus taken from HIV-positive people in 1986 to 1989 with other samples taken from people with HIV in 2002 and 2003. All the samples had been preserved in liquid nitrogen.
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After diluting each sample to ensure that they all contained the same number of virus particles, the researchers measured how quickly each replicated within T-cells taken from a single HIV-negative person. Because HIV targets T-cells, this serves as a measure of the 鈥渞eplication fitness鈥� of the different strains. Over a 12-day incubation period, the 1980s samples grew more quickly than their more recent cousins in 176 out of 238 direct comparisons (AIDS, vol 19, p 1555).
The researchers also ran the same competition in human dendritic cells, which are the first to be infected by HIV when it is transmitted sexually. That provides a measure of the 鈥渢ransmission fitness鈥� of HIV. Again, the older viruses survived and replicated better.
鈥淭he study shows nicely that the modern viral strains are outcompeted by the earlier strains in the laboratory,鈥� says Simon Mallal, director of the Centre for Clinical Immunology and Biomedical Statistics at the Royal Perth Hospital in Western Australia. However, the finding鈥檚 implications are far from clear.
For a start, it is not known whether the same would actually happen in the human body. Also, the Belgian researchers took care to ensure that none of the samples they tested came from people who had been treated with anti-HIV drugs. That allowed them to test how the virus may be evolving when left to its own devices, but it may not reflect what is happening in the real world, where drugs designed to limit the spread of HIV and the development of AIDS are becoming more common. These drugs will create their own selection pressure on the virus, and that may have a greater impact than any natural weakening of the virus, by creating drug-resistant strains.
A number of studies have found that people infected with HIV are not developing AIDS any more slowly than in the past, contrary to what would be expected if the natural virulence of HIV were diminishing. But neither is HIV progressing to AIDS more quickly. A widely publicised report earlier this year that a super-strain of HIV was infecting men in New York city, triggering early-onset AIDS, has since been debunked.
However, experts agree that not enough research has been done into the natural evolution of the virus for us to know for sure whether it is becoming more or less able to infect new hosts. In starting to fill that gap, the Belgian research has been warmly welcomed. 鈥淭his seems an important paper, and definitely suggests that something has changed in the virus since the 1980s,鈥� says Christophe Fraser, an epidemiologist at St Mary鈥檚 Hospital in London. 鈥淚t presents an important observation in an area which has been under-explored.鈥�
鈥淪amples of virus from the 1980s grew more quickly than their more recent cousins in 74 per cent of comparisons鈥�
In general, viruses are expected to become less virulent over time, as they have more chance of reproducing and spreading if they do not kill their host. For example, myxoma, the virus that causes myxomatosis in rabbits, has gradually become less virulent.
SIV, the virus that jumped from chimps into humans to become HIV-1, appears to have undergone a similar change, as it does not now cause severe clinical symptoms in chimps. The same applies to the strain of SIV that infects sooty mangabey monkeys, and jumped into people to become HIV-2. That suggests that SIV has become less virulent over time.
If so, we are seeing the end game of the SIV evolutionary story. As well as the virus itself becoming less virulent, it is likely that in the past, the only chimps or monkeys to have survived were those with strong genetic resistance to the virus. It could have killed large numbers of animals before becoming what it is today.
The same could conceivably happen with HIV. 鈥淏ut it would almost certainly take a very, very long time and would entail a lot of people dying of AIDS first,鈥� Fraser says. Lisa Frenkel, an infectious disease and virology expert at the University of Washington, Seattle, makes the same point. 鈥淚n theory, humans and the virus should co-evolve, so that HIV is less lethal,鈥� she says. 鈥淗owever, I do not expect to live to witness this transformation.鈥�
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