As reported in the December 15, 2007 Journal of Acquired Immune Deficiency Syndromes, researchers compared the rate of emergence of thymidine analog mutations (TAMs) and major protease inhibitor (PI) resistance mutations in adherent patients who remained on stable regimens containing a thymidine analog and/or PI after the onset of virological failure.

The investigators performed genotypic resistance testing using archived plasma obtained from patients having 0 or 1 TAM and/or 0 or 1 major PI resistance mutation at the onset of treatment failure.

Results

• The median duration of observed failure was 691 days.

• 41 patients were on thymidine analog regimens and 34 were on regimens containing PIs; 4 patients also used ritonavir (Norvir).

• New major PI resistance mutations emerged more rapidly than new TAMs (P = 0.0019).

• New TAMs emerged more rapidly in patients taking regimens that included thymidine analog other than 3TC (lamivudine; Epivir) (P = 0.0073).

• The emergence of TAMs and major PI resistance mutations did not differ if 3TC was not part of the regimen.

• The evolution of CD4 cell counts and plasma viral loads during virological failure was similar regardless of whether or not new TAMs or major PI resistance mutations emerged or - for thymidine analog-containing regimens - whether 3TC was used.

Conclusion

Major protease inhibitor mutations arose more frequently and rapidly than did TAMs in patients with sustained virologic failure who received lamivudine," the investigators concluded.

Veterans Affairs Greater Los Angeles Healthcare System, David Geffen University of California, Los Angeles School of Medicine, Los Angeles, CA; University of Texas Medical Branch, Galveston, TX; GlaxoSmithKline, Research Triangle Park, NC

1/12/07

References
M B Goetz, M R Ferguson, X Han, and others. Evolution of HIV Resistance Mutations in Patients Maintained on a Stable Treatment Regimen After Virologic Failure. Journal of Acquired Immune Deficiency Syndromes 43(5): 541-549. December 15, 2006.