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Genotype results, mutations & treatment
Sep 10, 2009

Hi Doc, first I wanted to thank you for your help and suppport in order to cope with this situation. I just got my genotype (subtype B) and "NO Resistance Predicted" for all the antiretroviral drugs (NRTI, NNRTI & PI). But at the end of the report it says "Other mutations detected" RT Gene Mutations: K103R, V179I, R211K, F214L. PR Gene Mutations: L10I/L, I62I/V, L63A/V. I wanted to ask you if this info means that I dont have any resistance eventhough I have certain mutations???. What kind of treatment do you recommend me? I am not on HAART yet since my numbers are still ok vl 25000, cd4 549, cd4 31%, cd8 750, cd8% 41%. 3 months ago: vl 10000 cd4 542, cd4% 35%, cd8 500, cd8% 35%. Is it common to develop more mutations and more difficult to fight like K103N??? how people develop mutations? just from not being adherent to the treatment or are there any other reasons??

Response from Dr. Young

Hello and thanks for your post.

If you're feeling well and not having any HIV related symptoms, with your CD4 count reproducibly above 500 and with an average-to-low viral load, there's no immediate need to start treatment.

The interpretation of your HIV genotype is correct; you're very astute in picking up the mutation called K103R-- this is at the key site that when mutated to K103N is associated with high level resistance to the non-nukes (NNRTIs) efavirenz (Sustiva, Stocrin, part of Atripla) and nevirapine (Viramune, part of Triomune).

Fortunately, while similar in name, the two mutations are quite different in effect. K103R is a so-called polymorphism (or natural genetic variation) not associated with significant drug resistance, but when present with another polymorphism 179D (not the 179I your virus harbors) can cause a decrease in NNRTI susceptibility.

Now, all that said, when my worry meter starts to increase about baseline or transmitted resistance, then I'll tend to prescribe a regimen containing a ritonavir (Norvir)-boosted protease inhibitor for first line treatment. Currently, we tend to use (in alphabetical order) atazanavir (Reyataz), darunavir (Prezista), fosamprenavir (Lexiva, Telzir), and much less commonly, lopinavir (Kaletra). Such regimens tend to have a lower tendency to be sensitive to baseline resistance and on the uncommon circumstance of treatment failure, less prone to develop high level cross resistance.

I hope this helps and wish you well,

BY



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