Separate lineages of HIV super-fast progressors
Investigators find patients by accident
Researchers at the University of Washington in Seattle made an interesting discovery during their routine study of a cohort of HIV-infected patients: Two men in the cohort were discovered to have two divergent subtype B sequences, indicating they had two independent viruses from independent people.1
"We sampled at six months post seroconversion and found only one of the lineages, and six months later the other lineage occurred," says David Nickle, MS, a research scientist in the department of microbiology. "That’s not to say the second lineage wasn’t there in the first time point, because it might have been there at a low frequency," Nickle explains.
The discovery included different lineages within HIV subtype B, meaning the lineages were independent strains and genetically distinct, Nickle says. Subtype B is the most common HIV subtype in the United States. "This is atypical," Nickle says. "You don’t expect this sort of pattern." After making the discovery, investigators applied for a grant to study the phenomenon and to study their hypothesis that dual infection leads to fast progression, since both dually infected patients were found to have progressed to AIDS within three to four years, Nickle says. Both patients died before the advent of highly active antiretroviral therapy, Nickle notes.
Dually infected patients typically aren’t discovered because most HIV tests are not designed to pursue this detail, he adds. "You have to be in a special cohort where people are sampling your blood to detect such a thing," Nickle says.
Investigators found that both subtype B clades co-existed and fluctuated in representation throughout the disease course, and that the two groups evolved at significantly different rates. "We did one experiment where you sample any independent virus in the database and see how far apart they are from each other, and these two lineages are as far apart from each other as any given random pair in the database, under subtype B," Nickle says. "What is very interesting is that these two different and separate lineages were maintained through time," Nickle says.
It’s common to expect that after many generations, one of the lineages will be lost through genetic drift, but that did not occur in the cases of the two patients, probably because the different HIV clades were using different resources within the patients, Nickle says. "So both are found in the blood, but they are not overlapping in resource use," Nickle explains.
Reference
1. Li F, Shankarappa X, He H, et al. HIV-1 evolutionary dynamics in a dually infected HIV-1 patient. Presented at the 9th Conference on Retroviruses and Opportunistic Infections. Seattle; Feb. 24-28, 2002. Poster 356-M.
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