The causes and consequences of HIV evolution

Rambaut A, Posasa D, Crandall KA & Holmes EC

(2004) Nature Reviews Genetics 5, 52-61.

Understanding the evolution of the human immunodeficiency virus (HIV) is crucial for reconstructing its origin, deciphering its interaction with the immune system and developing effective control strategies. Although it is clear that HIV-1 and HIV-2 originated in African primates, dating their transmission to humans is problematic, especially because of frequent recombination. Our ability to predict the spread of drug-resistance and immune-escape mutations depends on understanding how HIV evolution differs within and among hosts and on the role played by positive selection. For this purpose, extensive sampling of HIV genetic diversity is required, and is essential for informing the design of HIV vaccines.

  • The present genetic diversity of HIV is the result of multiple cross-species transfers to humans from African non-human primates.
  • HIV-1 has its origin in chimpanzees and is the result of three separate transfers to humans; by contrast, HIV-2 is most closely related to strains in the sooty mangabey and is the result of at least four transfers.
  • The most recent common ancestor of HIV-1 group M (the virus that causes the vast majority of infections globally) is estimated to have existed in the 1930s, although more 'fossil' viruses are needed to confirm this.
  • HIV-1 subtypes arise as the consequence of founder events and incomplete sampling.
  • Over the course of an infection, positive natural selection is the dominant mode of HIV evolution within a single patient.
  • Over the epidemic as a whole, stochastic processes are more important for the evolution of the virus between patients. There is little evidence that fitness differences among strains determine their population structure and distribution.
  • Genetic recombination is a fundamental mechanism for the evolution of HIV.
  • The development of drug treatments has greatly extended life expectancy and quality of life for those who are HIV positive but the development of drug resistance has been a major setback.
  • Recombination can rapidly bring together resistance mutations for multiple drugs during combination therapy.
  • The development of a vaccine for HIV has been a frustratingly slow process with the few candidate vaccines that have made it to phase III trials demonstrating no efficacy.
  • The high rate of evolution means that the pattern of diversity of HIV is changing at an alarming rate. Vaccines are therefore aiming at a constantly moving target.

Andrew Rambaut, 2007