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The workings of HIV

Jun 6, 2004

Hi Dr. Pierone:

I am trying to understand how HIV treatment works. If the treatment doesn't stop replication just controls replication what does this mean. If replication still occurs then how much HIV is still being produced and why can't you see this with viral load tests. And if wild type HIV is still being replicated then mutated HIV is also being replicated...if so wouldn't resistance occur naturally having nothing to do with someone skipping treatment?


Response from Dr. Pierone

Sometimes the terminology that we use when discussing HIV can be very confusing. The medications prevent HIV replication to varying degrees. The majority of people that are treated (and take the meds without fail) suppress replication to the point that we can no longer measure virus in the bloodstream. When someone has an undetectable viral load, this is the scenario that we are referring to.

There is evidence that people with an undetectable viral load may still have low level viral replication that is not picked up through commercially available blood testing. For example, if you do a lymph node biopsy on someone with undetectable virus and stain the slide for replicating virus you can sometimes find a rare cell that is producing virus. How much? All we can say is not enough to show up in the bloodstream.

When someone on therapy has an undetectable viral load there does not appear to be enough replication to fuel the development of resistance. This is why we see people that may have been undetectable for years and if they stop therapy they usually have wild type virus that grows with no hint of resistance.

Spontaneous mutations not related to HIV treatment are certainly part of the natural course of infection. This is related to an error-prone reverse transcriptase enzyme. These natural mutants are minority species and remain so because they are less fit than wild type virus. However, if monotherapy with an HIV medication is given (like the early days of AZT monotherapy) this minority mutant species through some happy accident of nature (happy for the virus, not the human) is resistant to AZT now has a selective advantage. AZT tends to kill off the wild-type virus and this natural mutant that can replicate in the presence of AZT can become the dominant virus. In the land of the blind, the one-eyed man becomes king.

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