Nature Medicine | Spoonful of Medicine

Tale of two twins highlights role of chance in HIV infection


HIV is notoriously unpredictable. The virus can prove fatal rather quickly in some individuals, while it remains at bay in a rare group of people known as elite controllers. Doctors have puzzled as to why some patients can fend off the virus better with drugs, while others progress despite receiving the best antiviral medications available.

A new study from a group led by Keith Crandall of Brigham Young University just south of Salt Lake City offers some explanation as to why HIV infection can produce such variable effects. Crandall’s team analyzed blood samples from a pair of identical twins who were both accidentally infected with HIV when receiving a contaminated blood transfusion at birth. “They were infected in 1983 — that was before most people knew HIV existed,” Crandall explains.

The virus mutates in the body over time. So Crandall and his colleagues scrutinized how the virus evolved in each of the twins using blood samples taken from birth up until 1998. They found that the viral sequence in the twins was about 1% genetically different by the end of that 15 year period. “That’s quite a significant difference,” Crandall says, noting that the genes of humans and chimpanzees differ by only about 2% to 4%.

What’s particularly important is that the striking difference in genetic makeup of the viral DNA was mirrored in the twins’ dramatically different disease progression. Whereas one twin had a normal immune system, with an average CD4 T-cell count of 860 cells per microliter of blood, the other twin had a poor CD4 count of 319 cells per microliter, and showed signs of drug resistance. “You have completely different clinical outcomes,” Crandall says. The findings, which appeared in BMC Evolutionary Biology in March, hit the newspapers today.

Previous research has emphasized how various selective pressures — such as drug treatment and other external factors — can cause the HIV virus to evolve within a patient. But since the twins were exposed to similar environmental factors, the new findings underscore the role that random genetic drift can have in determining how HIV mutates in the body. Crandall notes that drug makers and vaccine developers should wisen up about where these hotspots of genetic drift are in HIV, and take this more into account when designing treatments and prevention tools. “Understanding where those changes are is really important,” he says.

(Pictured: Keith Crandall)


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