Can someone explain "genotypes" to me?

[Sydney]

I've just read the thread on "discordant genotypes" - and I don't understand what this is about.
I've never had treatment before and am just about to start (Viramune + Kivexa/Epzicom).  My doctor didn't do any genotype testing prior to prescribing. Should this have been done?  What's the relevance to someone new to treatment? Should I delay starting meds and ask for genotype testing? 

Since I'm due to pop the first pills on Monday, I'd appreciate someone educating me on this.  Many thanks.

[newt]

Hello

A genotypic resistance test looks at the structure of your virus and how it has changed from normal 'wild type' virus. Different changes are associated with resistance to different drugs.

By checking the changes in your virus to these known mutations you get a good idea of which drugs are unlikely to work.

Although this test does not register very low levels of resistance, it can still be vital as a guide to choosing drugs for your next combination.

Although genotype tests cannot predict which drugs will work, they can predict which drugs will not or will be less effective

Guidelines in developed countries generally recommend a genotype resistance before starting treatment. Results take about a week. It is possible you had one done soon after diagnosis.

Genotype resistance tests give results as a list of mutations (if you have any).

These usually follow the format of a letter followed by a number followed by a letter - ie K103N.

The first letter stands for the amino acid that is normally expected at that position in the virus, ie K stands for lysine.

The number says where on the HIV DNA that the change has taken place.

In this example 103 refers to the 103rd amino acid in the reverse transcriptase section of the HIV genome.

The final letter stands for the new amino acid that the mutation makes, ie N stands for asparagine.

Not all mutations = resistance.

More imporant - if you are starting Kivexa, it is standard in developed countries to do a test for abacavir allergy. As abacavir is one of the 2 drugs in Kivexa, if this test is positive you should not use Kivexa.

Hope this helps

- matt

[leatherpoz]

Sydney,

Basically, it's checking the virus's DNA (or genomes) to see if there is any resistance to medication.

Here's a link to a description of "Genotyping" here on this site:

http://www.aidsmeds.com/articles/Resistance_4745.shtml

My doc did the genotype test to see what my virus is resistant to, or won't be affected by certain medication/treatments.  This allows him/her to get you on drug combo that will work and not be useless to a virus mutation that has made the virus immune to a drug.

It is an expensive test, takes about 1-2 weeks. If you don't have insurance, it can be cost prohibitive. Check with you doc and insurance company, if appropriate. I'm glad that my doc ordered it,and my insurance covers it, and we found out I had no known resistance to any of the meds and that opened many doors to courses of treatment.

First one (Atripla) didn't work for me because of the severe side effects (in *my* case, everyone's different on how they handle side effects, if any). Second (Viramune & Truvada) choice of meds is working much better as far as side effects, which have been minimal and manageable (gassy & poopy). I'll be having blood work in a couple of months to check my t-cells & viral load.

Best of luck, and hope you get what you need from your doc. Be honest, open and able to discuss any issues and concerns. If he/she isn't working with you in your healthcare treatments and options, time to find one you can have a good relationship with.

Mark

[J.R.E.]

Hello



More imporant - if you are starting Kivexa, it is standard in developed countries to do a test for abacavir allergy. As abacavir is one of the 2 drugs in Kivexa, if this test is positive you should not use Kivexa.

Hope this helps

- matt

Just to add a little more to what Matt stated above :

http://www.aidsmap.com:80/en/news/EDE2BB5D-B7BA-4DB7-9B11-460D7374CDC8.asp



Ray

[Sydney]

Matt,  Many thanks for taking the time to give me that detailed explanation - it was enormously helpful. And thanks too, Ray and Mark, for the extra added value. I suppose it's cliche by now, but I do feel incredibly supported having access to your knowledge and experience!  It literally brings tears of gratitude to my eyes. 

I have had the HLA-B*5701 test for sensitivity to Abacavir, and I'm negative on that - so no worries there.

After posting the question, I did a search of the topic, and I think I might understand why my doctor didn't get a genotype baseline prior to prescribing.

* Firstly, I seroconverted 23 years ago when there was no genotype testing available - so no seroconversion baseline.  And I gather that after a period of time the testing is not very informative because resistant strains may go dormant - only to be revived when challenged by medication.

* Secondly, although I can be fairly confident that my strain of virus is "treatment naive", I was concerned that other random mutations might result in drug resistance.  However, in one of the posts in the thread "Genotype and mutation" (April 15, 2007) Gerry said: "While the occurrence of random mutations are the general rule in HIV, these mutations in the absence of drug pressure do not lead to drug resistance.  The evolution of drug resistant mutations generally happens when viral replication continues to occur significantly in the presence of drug pressure from antiretrovirals".  And someone else said that genotype testing for baseline resistance "is mainly intended to rule out the presence of pre-existing (transmitted) resistance."

So can I conclude that I can be fairly confident that 23 years of random mutations (most probably) hasn't resulted in a drug-resistant mutation?  I'm going to ask for genotype testing anyway, and maybe I should hang off starting the meds until my mind is set at rest? Or maybe I'm obsessing!!??  What do you think guys?

(P.S. If there's a heaven, I'm going to meet you guys there!)

[newt]

I personally would get a genotype if you can

Heaven is a club in London and it is possible to get in even if you;s as old as me 

- matt