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differences between pheno and geno testing
Apr 29, 2001

Hi Dr. Little.

I am sero-postive male, 34 yo, treatment naive, 400 cd4, 180,000 vl, hav battled hereditary depression, considering starting, with a few questions; confused about the role of resistance testing in selecting my first line of meds.

1.) If /insurance wasn't an issue would you argue in favor of a resistance test prior to starting meds?

2.) If so, which type and why? Why would I do one, say a geno instead of a pheno? If I could do both should I? Would the results of each illustrate different things?

3.) What are the measurement <cut-off> points on the tests? What does this mean? For example, one regimen I am considering starting is Kaletra/PI and Trizivir/3 nukes; however I heard Kaletra isn't included, or doesn't have established <cut-off> points for some/all resistance tests. Is this true? What does this mean?

4.) Knowing what you know about me, would you consider starting me on something different than Kaletra/Trizivir. I like this cause low pill burden (4, twice daily), I have eractic schedule and do not want to touch Sustiva with its CNS, brain, I feel suicide stuff.

Thanks in advance,

Marcus Baton Rouge, LA

Response from Dr. Little

Good questions. In general, I believe that drug resistance testing should be done in RECENTLY infected people prior to starting antiretroviral therapy. The reason for this is that if the person who infected you had drug resistance, they could have passed this on to you (transmitted drug resistance). However, the ability to detect transmitted drug resistance may decrease over time - this has to do with the absence of therapy in the newly infected person and the tendency (we think) of the virus to revert to a more drug sensitive strain over time. What this means is that drug resistant virus is likely still present, but that we may be less and less likely over time to be able to detect it in an untreated individual who becomes infected with HIV. So, given that most people are not identified within one year of HIV infection (ie recent infection), I will assume that you have been infected for several years. The difficulty here is that as I just said, our ability to detect resistance in untreated people probably goes down over time, unfortunately, I do not know (nor do I think anyone knows) what this time scale is.

The good news is that if you have been infected for several years, the chances that you were infected with a drug resistant strain is really quite low (unless you know something about prior therapy in the person who might have infected you). Given this, most providers would probably not feel that resistance testing was indicated for you. On the other hand, if you have access to resistance testing and it will not cause financial hardship, it is not a bad idea to have one. The detection of drug resistance would be very helpful, the absence of detection does not particularly help. If you can handle these odds, then either test will work. In general, the phenotype test costs a bit more (like 3 times more), but both are excellent tests. I generally recommend the one that your provider is more comfortable interpreting (the phenotype test is easier to interpret by physicians not very familiar with drug resistance and reading genotype test results).

Regarding cut off points - this applies to phenotype testing and what it means is that we do not know (exactly) what level of reduced susceptibility predicts treatment failure for each drug. Again, if your provider is familiar with these tests though, what this means is that the results are not always black and white, they are occasionally in between. But, most drug resistance experts can probably make good recommendations even with in between results. Kaletra is now included in all the drug resistance assays that I am aware of, so I don't think that this should be an issue.

Regarding the choice of medications, the use of Kaletra and Trizavir is very potent and relatively easy in terms of schedule. I think it sounds excellent.

Stop antivirals while await resistance test results
Combivir and Sustiva

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