HIV particles (green) budding from a cell.
HIV,
which is spread through blood, semen, and other bodily fluids, is a prime
example disease evolution in the modern age.
Its rapid and progressive change in the face of attempted cures has
baffled scientists for years. For
instance, after the first antiretroviral drug active against HIV, zidovudine,
came out, resistant HIV strains were found in new patients within six years. But one may wonder why HIV is so much better
at evolving in response to drugs than other bacteria and viruses. The answer is two-fold. The first aspect comes from just how virulent
HIV is. Its production of new virus and overall
virus turnover is extraordinary.
According to Clavel and Hance, the lymphoid tissue of most untreated
patients has between 107 and 108 infected cells, each of
which has a half-life of one to two days.
To maintain this level, HIV must infect many new cells
continuously.
The second aspect is the rate of mutation between replications of the virus. When HIV infects a human cell, it hijacks its machinery to create more HIV. The reverse transcription process it uses, however, is very error prone. For each copy of the virus that is created, at least one error occurs – a mutation. While this may not seem significant, when it is extrapolated over the huge population of HIV found in someone’s body, it leads to a diverse set of HIV particles with a diverse set of traits. Some of them are weaker than your average virus; some are stronger and more effective.
The second aspect is the rate of mutation between replications of the virus. When HIV infects a human cell, it hijacks its machinery to create more HIV. The reverse transcription process it uses, however, is very error prone. For each copy of the virus that is created, at least one error occurs – a mutation. While this may not seem significant, when it is extrapolated over the huge population of HIV found in someone’s body, it leads to a diverse set of HIV particles with a diverse set of traits. Some of them are weaker than your average virus; some are stronger and more effective.
Word Count: 539
Sources:
Clavel, Fracois, and Allan J. Hance. "HIV drug resistance." New England Journal of Medicine 350.10 (2004): 1023-1035.
"HIV/AIDS Statistics and Surveillance." Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 19 December 2012. Web. 20 February 2013.
Image source: http://upload.wikimedia.org/wikipedia/commons/1/1a/HIV-budding-Color.jpg
If an error occurs for every copy of the virus created, that means HIV has a mutation rate of 50%. I wonder if I misunderstood this passage, because if 50% of each generation are mutants, HIV can't be very effective, since most mutations would be either neutral or slightly deleterious. Also, HIV uses our cellular machinery to replicate, and human cells don't make a mistake for every correct copy of genetic material they produce.
ReplyDeleteDoes anyone know if HAART type "medical cocktails" are used to treat other illnesses where drug resistance is an issue?
ReplyDeleteI've actually read in one of the blogs that the treatment of malaria is taking this direction -use of medical cocktails
DeleteIt seems like combination therapy is also used for tuberculosis, leprosy, cancer and malaria. The positive side of using this mode of treatment is that it is less likely to develop drug resistance.
ReplyDeleteI was not aware that there was once an effective treatment for HIV but it does not surprise me that drug resistant strains mutated based on how virulent HIV is. The concept of treating such a dangerous virus with multiple medications is also slightly worrying. Although it is true that it is unlikely that the virus will be resistance to all the medications, exposing the virus to multiple medications will promote it to acquire resistances faster since it the treatments do not fully eradicate the virus.
ReplyDeleteRecently, HIV was "functionally cured" in a toddler after receiving high doses of three antiretroviral drugs, in hopes of controlling the virus passed down from her HIV positive mother. Many researchers believe the timing of the treatment is what was key in the success of the "cure." It'll be interesting to see if this finding can translate into a more efficient and successful way of curing HIV in those already infected with it, or if it will only (or not) prove effect in treating HIV at its immediate onset, which could still prove beneficial to those who are recently affected. Here is the CNN article: http://www.cnn.com/2013/03/03/health/hiv-toddler-cured/index.html
ReplyDeleteAnother blog post mentioned using patient's dendritic cells (immune cells that function to process antigen materials) as an immunotherapy agent to target evolving strains of cancer. That method of treatment definitely has potential in combatting HIV where drug resistance is a huge problem as a well.
ReplyDeleteThis could help manage the disease but I still think HIV would evolve so fast for the dendritic cells to keep up.
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