The Origin of HIV in the Americas

Blogging on Peer-Reviewed ResearchThe mainstream media has been reporting on this paper (open access at PNAS) on the hunt for the origin of HIV in the Americas.

The surprising result was the finding that HIV first came to the United States from Haiti (rather than the previous origin which was thought to be a flight attendant from Canada) between 1966 and 1972, and flew under the radar of public health authorities for over a decade. The infection, spread initially by heterosexuals from Haiti, went undetected from as early as 1966 until 1981 and then only because it had jumped into a highly susceptible population. This article is rather humbling, because in perhaps the medically advanced country in the world, it evaded detection for so long until it finally created an epidemic in the male homosexual population.

So how did they figure this out?

Basically, they used a combination of an evolutionary understanding of viral spread through populations (with the understanding that new mutations and new strains occur with time) combined with archival samples of blood from early victims of the disease which allowed the authors to track the virus down to Haiti.

Critically, the “group M, subtype B” of HIV, which though less frequent than the pandemic virus, indicated the original pattern of HIV spread, from Africa, to Haiti, and ultimately the US and the rest of the world. By testing the sequences of the essential env and gag genes, which encode envelope proteins and group-specific antigen structural proteins (the viral matrix, capsid and nucleoproteins) respectively, they could identify where exactly where they branched off from the original viral strain from Africa. If the “Haitian spread” hypothesis were correct, one would expect the subtype B virus to be present in these older samples, and more closely resemble the African subtype.

Sure enough, this is what they found:

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In the above analysis of the branching of env genes, the green branches represent the Haitian genotypes and the bolded text represent the archival samples from early HIV cases in Haitian immigrants. Consistent with the hypothesis of a Haitian origin, they represent early branch points from the African subgroup. Based on the author’s analysis, this spread of genotypes in Haiti makes the probability of a non-Haitian origin is less than one in a thousand. If the alternative hypothesis were correct, one would expect that early samples would represent the pandemic clade from the US, and it would be more closely related to the original African virus. The authors tested other models of phylogenetic analysis and they linked the viral origin to Haiti even more strongly.

Using molecular clock analyses to determine when would have expected these mutations to have evolved is what led the researchers to believe the new strains originated in the Americas in the late 60s to early 70s.

I’m less surprised by this, given the long incubation time of the virus, that it would ultimately evade detection by public health authorities for almost 12 years. Not only does the incubation time figure into making it difficult to link the virus to the illness, but if you think about it, the exposure that caused the illness is also in distant memory of the patients making it unlikely people would consider a link between sexual partners and the presence of the disease. In retrospect, a pandemic was almost inevitable, as it would have been nearly impossible to link the behavior with the illness without large numbers of sick patients to compare common experiences. The authors even hypothesize that the reason the virus took so long to be identified was that it initially spread from a heterosexual population, which was low risk for infection, allowing it to spread slowly and undetected throughout the US. However, once it spread to the male homosexual population, which was high-risk for transmission, there was a rapid increase in the number of cases which made it possible for doctors to link the cause to the effect.

It’s a fascinating, and ultimately humbling story. HIV was spreading throughout one of the most advanced countries in the world for over a decade, undetected. Not until a highly-susceptible population acted as the canaries in the coal mine were we able to realize there was this subtle, deadly infection, capable of destroying one’s immune system years after the initial exposure, which for most patients, would be nothing but a distant memory.

A final note, I apologize if I get details of this story incorrect, viral genetics and phylogeny are not my field, but it’s such an interesting story to me as a med student that I felt I had to relate it. I am glad of any corrections to my interpretation of this paper and look forward to see the take of experts like Tara to see if they resemble my own.

M. Thomas P. Gilbert, Andrew Rambaut, Gabriela Wlasiuk, Thomas J. Spira, Arthur E. Pitchenik, and Michael Worobey The emergence of HIV/AIDS in the Americas and beyond PNAS published November 1, 2007, 10.1073/pnas.0705329104