Nov 16, 2011
I'm trying to learn all I can about mutations, resistances, tropism, etc. Lately, I've been hearing many talk about archived resistances. I've heard some say you could have mutations that have gone hidden after being infected for several years and treatment naive that don't show up on the resistance tests.
So, does this mean you could think you're good to go on all regimens or most of them, and find out that you actually have fewer regimens that will work due to these archived mutations?
And, holding off on meds because you have good/decent numbers doesn't mean you could develop more mutations in the meantime, right? I mean, the mutations/resistances that affect HAART choices are there from the get-go?? Having said that, I have read where you could pick up another strain of HIV that is resistant, but I'm not talking about that situation.
One last question--the tropism? That is when the virus begins using the other receptor? Is that an issue with which meds would work?
Thanks for taking the time to help educate all of us. We do appreciate it very, very much. I suppose I'm wondering if these archived mutations could pop up and affect a regimen you thought would work, does this happen very often or just rarely?
Response from Dr. McGowan
Thanks for your excellent questions.
HIV usually grows best when it does not carry mutations in it's genes. This occurs when a person is not taking any medicines. The non-mutant (or "wild-type" virus) has the advantage over other strains that carry resistance mutations.
However, when conditions change...such as when medications are started, all the wild-type virus gets killed off. That is when the resistant virus may have the upper hand and, if it able to survive in the presence of the meds, will start to grow and make copies of itself. When it copies itself it adds additional mutations which help it adapt to the meds and increase its level of resistance.
The "archive" is made up of CD4 lymphocytes called Memory Cells. These cells persist for years (decades) and are responsible for protecting a person from all the infections and illnesses they have encountered over their lifetime. That is why we don't get chicken pox every yaer, and why vaccinations can give lasting protection. This is teh function of the Memory CD4 cells. When HIV infects these cells, it inserts its' genes into their chromosomes and the virus genes also can persist for years in hiding. In this way their is a "library" of all the starins of HIV that a person has carried over the years, including all the past resistant strains. If a person tries to use a past medication that had failed due to drug resistance, the resistant starin can "wake up" from the archive and grow in the presence of the medicine aince all the "wild-type" virus gets killed off. When the meds are stopped, then the wild-type (non-mutant) starin comes out of the archiev and out-competes the resistant strain. The resistant strain then falls into the minority. If the resistant starin drops to less than 10-20% of the overall population it can be missed by the resistance test (the genotype or phenotype).
Without being on medicine there is no risk of adding new resistance mutations because the virus is not reacting against anything. The mutations arise as the virus grows in the presence of the meds....strains with mutations that provide a growth advantage will predominate and one by one mutations get added making each successive strain more adapted to the medicines.
The only excepton is with tropism. As you mention, tropism is the term that refers to which pathway the virus uses to enter the CD4 cell: either through the CCR5 or the CXCR4 co-receptor. Most virus in the early stages of infection uses CCR5, which we can block with CCR5 antagonists (maraviroc). But over time, even without being exposed to the medicine, the virus can adopt the ability to use the CXCR4 co-receptor. So the tropism test should always be done or repeated just before you would plan to use these meds.
I hope this helps explain some of these tricky concepts.
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