Response Sent to the Proceedings of the National Academy of Science
Sampling error and bias in the report on the emergence of HIV/AIDS in
the Americas and beyond
Bookmanlit's response to:Gilbert M-T-P, Rambaut A, Wlasiuk G, Spira T-J, Pitchenik A-E, Worobey M (2007) The emergence of HIV/AIDS in the Americas and beyond. Proc. Natl. Acad. Sci USA
Adapted from our response to the Editor of Proceedings of the National Academy of Science to highlight the flaws in their study tracing the origin of one subtype of HIV to Haiti.
Sampling errors of Gilbert et al may leave HIV-1-Subtype-B’s origin unanswered. They compared portions of HIV-1-Subtype-B sequence in 5 Haitians to 117 presumed non-Haitian subjects from 19 countries1. Country of testing is not synonymous with origin of subjects tested. Because of early advisories2, governments may have preferentially tested Haitian immigrants3 and their nationals travelling from Haiti. Confusing country for national origin creates bias that minimizes the biodiversity of the virus, misleading the authors to proclaim Haiti as the unique source of the HIV-1-Subtype-B pandemic.
Biodiversity in Haiti is not proof that the virus had a longer history there. Biodiversity is a function of the number of generational divisions a virus has undergone. HIV-1-Subtype-B may have initially proliferated more rapidly in Haiti, having found a susceptible population lacking CCR5 mutation, a gene that can limit the acquisition and proliferation of the virus within its host4. The author’s dating of HIV-1-Subtype-B’s origin relies on a “relaxed-molecular-clock” model that doesn’t account for the ticking of this clock at different rates due to differing population susceptibility.In addition, since Haiti has a more youthful population than the US, the sexual behavior of the two populations alone may account for the different growth rate of the disease in the two populations, having little to do with time of introduction of the infection to either country.
The history of HIV-1-subtype-B infection may be important for preventing future pandemics, but is not a prerequisite for vaccine development as the authors suggest. What's needed is knowledge of host response to infection while monitoring the changing antigenic profile of the virus in the population to be vaccinated.
We therefore reject the authors’ conclusions1 that HIV-1-Subtype-B virus came to the U.S. through Haiti and that this information is essential for developing vaccines or any other form of treatment.
1 Gilbert M-T-P, Rambaut A, Wlasiuk G, Spira T-J, Pitchenik A-E, Worobey M (2007) The emergence of HIV/AIDS in the Americas and beyond. Proc. Natl. Acad. Sci USA
2 Pitchenik A-E, Fishl M-A, Dickinson G-M, Becker D-M, Fournier A-M, O’Connell M-T, Colton R-M, Spira T-J (1983) Opportunistic infections and Kaposi's sarcoma among Haitians: evidence of a new acquired immunodeficiency state. Ann Intern Med. 98(3):277-84.
3 George J-A, (1993) Detention of HIV-Positive Haitians at Guantanamo-Human Rights and Medical Care. N Engl J Med. 329 (8):589-592
4 Kahn, J-O, Walker G-D (1998) Acute Human Immunodeficiency Virus Type 1 Infection. N Engl J Med. 339 (1):33-39
Disclosure: The Editor of the Proceedings of the National Academy of Science did not accept our response for publication . The Editor argued that the difference in incidence of CCR5 mutation between the American population and the Haitian population is insufficient to account for a different pattern ofHIV growth in the two populations.We regret not having pointed out to them that beyond differences in genetic susceptibility, demographic variations, namely Haiti’s more youthful population would result in a different pattern of sexual activity which itself could account for the differences observed in the growth of HIV in the two populations. Recognizing this demographic difference undermines the model used by the authors to calculatethe age of HIV in the Americas.At the time that we wrote the original response, the co-authors worked for the University of Miami.