HIV drug resistance

HIV drug resistance occurs when microevolution causes virions to become tolerant to antiretroviral treatments.

Limited effects of current drugs (outdated)

HIV develops resistance when it evades the effects of these treatments.[1] A recent study estimated the percentage of the American HIV positive population with some form of drug resistance to be 76.3%.[2] Certain intrinsic features of HIV facilitate its widespread resistance, most importantly its extremely high mutation rate.

Developing resistance (less fit mutations compared to wild type)

As a retrovirus, HIV uses the enzyme reverse transcriptase to synthesize DNA from its RNA genome and lacks a mechanism for correcting errors made while reproducing its genome.[1] As a result, HIV replicates its genome with the highest known mutation rate of any 'living' organism.[1] This creates an ideal situation for natural selection to act on the HIV population, as genetic variation is the raw material for natural selection.

These mutations accumulate over generations and in populations, resulting in the great genetic variation within populations of HIV, and an increased probability of a virion developing an evolutionary selective advantage over other virions.[1] Natural selection then acts on HIV by selecting for virions with higher fitness, as all others are eventually killed off by drug treatments.[3] The virions that are able to escape the harmful effects of the drug then create an entirely new, drug resistant population.

The virions reproduce until the patient has a population of viruses as large as they originally did before treatment reduced these numbers. This creates a cycle in which patients first experiences success with treatment, as their viral levels decrease, then experiences a decline in treatment effectiveness as the virus develops resistance and rebuilds its population of virus particles.

Contemporary treatment issues

Currently, resistance occurs in all antiretroviral treatments, if non compliant[3] This has resulted from HIV evolving in response to selection from antiretroviral drug treatments that eliminate all but the most fit viruses. Current medical and scientific opinion is mixed on the most effective treatment methods, but is focused on drug cocktails and the importance of first-line regimens.

The World Health Organization advocates a public-health approach rather than an individual-based approach to HIV treatment in order to make treatment more uniform and more available to all patients throughout the world.[4] Among treatment methods, the World Health Organization acknowledges the importance of successful first-line treatments.[4]

First-line treatments are known to affect the virus’ future response to other treatments, making the effectiveness of first-line treatments an issue of vital importance.[4] The most successful treatments are combinations of three drugs used simultaneously, as this greatly reduces the probability of the virus developing resistance.[5]

See also

References

  1. 1 2 3 4 Freeman, S., and J. C. Herron. 2007. Evolutionary Analysis. 4th ed. A case for evolutionary thinking: understanding HIV. Pearson Benjamin Cummings, San Francisco, CA.
  2. ↑ Richman, D. D., S. C. Morton, T. Wrin, N. Hellmann, S. Berry, M. F. Shapiro, and S. A. Bozzette. 2004. The prevalence of antiretroviral drug resistance in the United States. AIDS. 18: 1393–1401.
  3. 1 2 Kozal, M. J. 2009. Drug-resistant human immunodeficiency virus. Clin Microbial Infec. 15 (Suppl. 1): 69–73.
  4. 1 2 3 Gilks, C. F., S. Crowley, R. Ekpini, S. Gove, J. Perriens, Y. Souteyrand, D. Sutherland, M. Victoria, T. Guerma, and K. De Cock. 2006. The WHO public-health approach to antiretroviral treatment against HIV in resource-limited settings. Lancet 368:505–510.
  5. ↑ Cane, P. A. 2009. New developments in HIV drug resistance. J Antimicrob Chemoth. 64 (Suppl.1): 37–40.
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