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Mutations?
Aug 24, 2007

I'm trying to understand HIV mutations. Do mutations result only from failed medications, or do they occur spontaneously as the virus progresses? (Or both?) Was the original wild strain in the 70s/80s free of mutations?

Can some mutations be the direct result of the introduction of specific medication or class of medicines? If so, can this provide a marker for the approximate age of a virus or time of exposure? In other words, if medicine X was introduced in 1990 resulting in mutation X in the 1990s, would having this mutation indicate an exposure to the virus after the introduction of drug X?

Last question is more personal: the mutations listed in my genotype test (L10I, I13V, G16E, M36I, A71T) and susceptibility ratings indicate possible resistance to only one drug, Atazanavir. Does this mean that all the other drugs are in play for the future, or will future genotype tests be needed to look for new mutations?

Thank you for your time.

Response from Dr. Daar

Thank you for this post. What a great question. I wish I could sit down with you for an hour and discuss each of these issues since they are all very interesting. Sadly, I have a few paragraphs so I will give it a go and hope that I address at least most of your questions.

While HIV is HIV, it is genetically somewhat different in everyone. People start out with a virus that replicates at high levels, during the course of which mutations occur by chance in a random way. Whatever virus is present within the given individual is "wild type" for that person but is always changing in small ways over time. By chance select mutations can emerge that provide an advantage for the virus. The best example of this is when someone is on anti-HIV medications and a mutation develops that results in resistance. In this setting, this new mutated virus becomes predominant in the blood, at least until the drug is stopped after which the original "wild type" virus may return as the most common virus in blood. It is important to note that the virus that was resistant to the drug does appear to persist in the body forever and will rapidly be selected for if that drug is restarted. In addition, occassionally someone can become infected with a drug resistant virus that is present in the blood of someone who is on therapy. Based upon this one really can not use these drug resistant mutations very effectively to define when someone was infected. A topic for another discussion is that scientist have used the overall genetic variabilty to pinpoint the time HIV may have emerged from chimp virus some 70-80 years ago.

With regards to your mutations. In general, most of these occur by chance in people who have never been on drugs before and would not typicaly be associated with resistance to any of the protease inhibitors. Consequently, I would expect that your virus is susceptible to all of the drugs in this class. This will be helpful when you ultimately sit down with a provider to choose an effective regimen since you should have many options.

Best, Eric


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