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Resistance Mutation 103Q
Apr 2, 2004

I had a resistance test prior to starting HAART, showing resistance to nevirapine/Viramune with mutation 103Q. I have read that some of the mutations at 103 are cross-resistant but I have not been able to find any specific information on the 103Q mutation. Are all mutations at 103 cross-resistant in the NNRTI class? Should I be worried that this mutation could confer resistance to Sustiva, and in turn cause my regimine to fail sooner rather than later? Should I consider swaping out the Sustiva for a PI before that happens?

I'm 36, my current (and only) regimine is Sustiva, Epivir, & Viread. Started meds 4/03 with CD4 of 310 & VL of 67,700. My VL took five months to fall to undetectable and has stayed there so far. So, after 11 months on treatment I'm undetectable w/ CD4 at 552. I've never missed a pill, but have been late a few times. So overall I'm doing well...just wondering if I should be proactive in switching meds.

Thanks in advance for any insight you can give!

Seattle Dude

Response from Dr. Sherer

We have recently observed that novel mutations at the 103 locus - like the K103Q that you describe - can affect NNRTIs. The K103Q had a prevalence of <1% in an analysis of two large databases, so it appears to be quite uncommon. Fortunately, in this analysis, no clear impact of the K103Q was observed on either efavirenz or nevirapine, and your clinical history suggests that your virus is responsive to an efavirenz regimen. I would suggest that you stay with this regimen and discuss these issues with your doctor.

Note that it is possible that in your case, the K103Q reduced susceptibility to nevirapine, particularly if you had a phenotype test, in which your virus was tested against NVP. If your test was a genotype, then the interpretation of the presence of the K103Q mutation would depend on what alorithm the test intrepretation was using. I would discuss this question with your doctor.

To complete the description of this study, it was an analysis of >75,000 clinical isolates from the Virco database (>60,000 isolates) and the British Columbia (Canada) cohort (15,000 isolates). The most common mutation was the K103N (25% of mutations).

Of mutations at the 103 locus, 6% were K103R, 3% were K103S, and <1% for each K103T, Q, H. Loss in susceptibility (fold change)associated with these mutations was as follows: Efavirenz: K103S (10x), K103T (10x), K103H (>50x) Nevirapine: K103S, T, H (>50x each) NRTIs: no effect

The investigators concluded that rare mutants at 103 locus associated with a loss of NNRTI susceptibility were the K103S, T, and H. There was no impact of the K103Q mutation observed in this study.


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