Budding HIVLast week I talked about the evolution of noroviruses, which have repeatedly thrown out new strains and caused new epidemics over the past 20-odd years. In contrast — and rather unexpectedly, at least for me — it seems that HIV is not changing its virulence over time; at least, not in North America.

You can think of reasons why HIV “should have” either increased or decreased its virulence since entering North America. For example, HIV entered the human population relatively recently; perhaps it’s still adapting to its new host, and is learning how to more efficiently infect us. On the other hand, it’s widely (though incorrectly) believed that pathogens inevitably evolve toward reduced virulence; perhaps HIV follows this path as well. (Similarly, at least in theory, the human population could be adapting to the virus, something that certainly happens with other species and viruses. However, 30 years or so seems pretty short for this kind of evolution in humans.) The HIV epidemic in North America started in the early 1980s, which has given the virus lots of time to evolve one way or another (compare to noroviruses, which have thrown out six epidemic-causing variants1 since 1995).

Experimental evidence has pointed in all directions — some suggests that HIV is becoming less virulent, some that it is becoming more virulent, and some says it’s staying the same. There are all sorts of complications in measuring this. What exactly is “virulence“, anyway — time to death? Death rate? Rate of replication? Transmission? In the absence of a suitable animal model the most direct answers can’t really be tested directly. What’s more, because of the vast improvement in anti-retroviral treatment over the years, it’s hard to compare clinical course. And the virus is intrinsically so variable that you’d need large numbers just to be sure you’re analyzing a real trend.

HIV ModelA recent paper in PLoS ONE2 tried to resolve the question by looking at clinical correlates of virulence, and they reached the conclusion that the virus hasn’t changed significantly (in terms of virulence, by this definition) over time:

We tested for associations between calendar year of seroconversion and three prognostic markers of disease progression in the MACS cohort between 1984 and 2005. Our results showed no significant trends in set point plasma viral RNA load, CD4 cell count after seroconversion, or the rate of CD4 cell decline in the first three years after seroconversion. Moreover, estimates of change in these markers over time were very close to zero. Thus, the results of this study do not support the hypothesis that there has been any important change in the virulence of HIV-1 over this time period in this cohort.

Is this study likely to end the controversy? I really doubt it; there are just too many limitations in this kind of study. (I do think, though, that it helps establish bounds: it’s unlikely that HIV virulence has changed massively either way since it arrived in North America.) Nor does it help us going forward: HIV strains with different virulence may be arising even now. Still, it’s an interesting finding. My own prejudice would have been that HIV virulence would be increasing, but I’m happy to set that aside for now.

  1. Simplified![]
  2. Herbeck, J.T., Gottlieb, G.S., Li, X., Hu, Z., Detels, R., Phair, J., Rinaldo, C., Jacobson, L.P., Margolick, J.B., Mullins, J.I., Tripathy, S. (2008). Lack of Evidence for Changing Virulence of HIV-1 in North America. PLoS ONE, 3(2), e1525. DOI: 10.1371/journal.pone.0001525[]