In Botswana and South Africa, two countries severely affected by the HIV epidemic, evidence has been collected suggesting that HIV is subject to a kind of tradeoff: the virus may develop resistance to patients’ natural immunity, but does so at the cost of decreased virulence. This finding, the result of a study of two populations with contrasting HIV histories, is raising hopes that wider application of antiretroviral therapy may increase pressure of HIV, causing it to develop additional resistance—and grow even less virulent.

Across Botswana and South Africa, over 2,000 women with chronic HIV infection participated in a study that focused on the protection offered by HLA-B*57, a gene that expresses a human leukocyte antigen (HLA) associated with slower progression of HIV toward AIDS. HLAs enable the immune system to differentiate between the human body’s proteins and the proteins of pathogens.

The study, which was led by researchers from the University of Oxford, showed that in Botswana, where HIV has evolved to adapt to HLA-B*57 more than in South Africa, patients no longer benefit from the gene’s protective effect. However, the research team’s data show that the cost of this adaptation to HIV is that its ability to replicate is significantly reduced, therefore making the virus less virulent.

This finding was presented December 1 in the Proceedings of the National Academy of Sciences, in an article entitled, “Impact of HLA-driven HIV adaptation on virulence in populations of high HIV seroprevalence.”

“In Botswana, where the epidemic started earlier and adult seroprevalence has been higher, HIV adaptation to HLA including HLA-B*57/58:01 is greater compared with South Africa (P = 7 × 10−82), the protective effect of HLA-B*57/58:01 is absent (P = 0.0002), and population viral replicative capacity is lower (P = 0.03),” wrote the authors. “These data suggest that viral evolution is occurring relatively rapidly, and that adaptation of HIV to the most protective HLA alleles may contribute to a lowering of viral replication capacity at the population level, and a consequent reduction in HIV virulence over time.”

The research team, which included scientists from South Africa, Canada, Tokyo, Harvard University and Microsoft Research, also considered the impact of antiretroviral therapy on HIV virulence: “Models developed here suggest distinct benefits of ART, in addition to reducing HIV disease and transmission, in driving declines in HIV virulence over the course of the epidemic, thereby accelerating the effects of HLA-mediated viral adaptation.”

Lead scientist, Professor Phillip Goulder from the University of Oxford, said, “This research highlights the fact that HIV adaptation to the most effective immune responses we can make against it comes at a significant cost to its ability to replicate. Anything we can do to increase the pressure on HIV in this way may allow scientists to reduce the destructive power of HIV over time.”