• Poster 740: Common, Rare, and New HIV-1 Resistance Profiles Observed in Routine Clinical Practice: A Survey of over 5,000 Isolates and the Characterization of a Novel 3TC Resistance Mutational Profile Lacking 184V (Authored by K. Hertogs, V. De Vroey, C. Van Den Eynde, P. Dehertogh, A. Vanbloor, V. Miller, T. Alcorn, B. Larder, and S. Cauwenberge. VIRCO, Mechelen, Belgium; VIRCO, Cambridge, UK; J.W. Goethe Univ., Frankfurt, Germany; and LabCorp, Raleigh, NC)
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• Poster 750: Comparison of Viral Resistance Emerging over 48 Weeks of Therapy with IDV/COM vs. ABC/COM (Authored by T. Melby, S. Tortell, D. Thorburn, A. Cutrell1, G. Pearce, B. Spreen, S. Lafon, and E. R. Lanier. Glaxo-Wellcome, Res. Triangle Park, NC; and Glaxo Wellcome, Greenford, UK)
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Poster 740: Common, Rare, and New HIV-1 Resistance Profiles Observed in Routine Clinical Practice: A Survey of over 5,000 Isolates and the Characterization of a Novel 3TC Resistance Mutational Profile Lacking 184V

Genotypic and phenotypic resistance assays are fairly new, and their interpretation is still an art. Genotypes, in particular, are difficult to interpret, and the importance of individual mutations or patterns of mutations is frequently not well defined.

In this study, over 5,000 phenotypic assays were compared in order to correlate specific mutations on the genotypes with phenotypic resistance (full sequence ABI genotypes were performed, rather than the typical commercially-available genotype which looks only at selected mutations).

Overall 85% of the tests showed resistance to at least one class of drugs: 10% to one class, 20% to two, and 70% to all three classes. Amongst the RT- associated mutations, 215 (46%) and 184 (42%) were the most common. The most common NNRTI mutation was 103 (21%) followed by 181 (15%). The mutation at position 10 (31%), a secondary mutation was the most common protease inhibitor-associated mutation, followed by 82 (16%) and 46 (15).

Multi-drug resistance (MDR) mutations against RT were relatively rare: 151 was found in 1.7% of sample, and the 69 insertion in less than 1%.

Although mutations in the NNRTI class are frequently considered to be "cross-class," 21% of those with an NNRTI mutation were still sensitive to at least one drug in this family.

The correlation of genotypic and phenotypic assays, such as this, will be useful in determining the significance of new, rare and complex mutation patterns, as well as the interrelationships of multiple mutations. Unfortunately, the expense of these tests limits our ability to do these correlations on a regular basis.

(Despite the title, I couldn't find the description of a novel 3TC- associated mutation.)

Poster 750: Comparison of Viral Resistance Emerging over 48 Weeks of Therapy with IDV/COM vs. ABC/COM

Identifying resistance mutations can be important in designing subsequent regimens. The likely mutations that develop on any given regimen are not always obvious.

This study looked at mutations developing in treatment failures on protocol CNA3005, a comparison of indinavir and combivir with abacavir and combivir. In each arm approximately 5% of patients were considered virologic failures, with viral load >400. Of interest, these failures did not return to their baseline viral load: the average viral load after failure was 1.5 logs less than baseline (1.8 log in the abacavir arm; 1.3 in the indinavir arm). 30% of failures had wild-type virus, implicating factors other than resistance.

Overwhelmingly, in both arms, the first mutation to develop was the 184 mutation associated with 3TC resistance. Other mutations, against AZT/abacavir or indinavir, only developed later in the trial. This would seem to leave open the option for effective salvage therapy.

These results give hope that "failure" of a first treatment regimen may not be the disaster that we presume. Early evaluation and intervention would seem to provide hope for successful rescue.