HIV AIDS drug resistance
Overview
The ability of HIV to mutate and reproduce itself in the presence of antiretroviral drugs is called HIV drug resistance. HIV Drug Resistance occurs when microevolution causes virions to become tolerant to antiretroviral treatments.
Current scenario
Nearly all drugs currently used to treat HIV eventually stop working when patient develops resistance to ART. 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]
Mechanism of drug resistance
- 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.
Reference
- ↑ 1.0 1.1 1.2 1.3 Freeman, S., and J. C. Herron. 2007. Evolutionary Analysis. 4th ed. A case for evolutionary thinking: understanding HIV. Pearson Benjamin Cummings, San Francisco, CA.
- ↑ 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.
- ↑ Kozal, M. J. 2009. Drug-resistant human immunodeficiency virus. Clin Microbial Infec. 15 (Suppl. 1): 69-73.