Background: Resistance to antiretroviral therapeutics (ARTs) is one of the key factors limiting drug efficacy. As specific drugs increase and decrease in usage, the prevalence of mutations associated with those drugs might also be expected to rise and fall. Here we have longitudinally examined the relative frequency of specific mutational patterns in a large database.

Methods: The LabCorp HIV Data Warehouse (1-1-99 to 7-1-02) was examined for the incidence of specific mutations and combinations of mutations associated with resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside RTIs (NNRTIs), and protease inhibitors (PIs). A total of 37,907 genotypes were included in this analysis. All primary mutations associated with ART resistance were examined. Preliminary statistics were calculated using 2-sided Cochran Armitage trend tests.

Results: Several mutations associated with resistance to NRTIs are shown below as examples. All major patterns will be presented.

Year	N	K65R	L74V	Y115F	M184V	41/210W/215Y
1999	5,324	0.7%	9.8%	0.6%	44.0%	17.3%
2000	5,816	0.8%	9.3%	0.9%	42.3%	14.4%
2001	16,590	0.9%	7.9%	1.0%	44.3%	12.2%
2002*	10,177	1.7%	7.8%	1.4%	41.2%	11.3%
Fold**	N/A	2.5x­	0.2x¯	2.5x­	<0.1x¯	0.4x¯

* Through July
**Fold change 1999–2002

 

K65R and Y115F increased similarly from 1999–2002 while the M184V started and remained prevalent. Thymidine analog mutations decreased steadily as shown for 41L/210W/215Y. This may be attributable to decreased dual NRTI therapy and shorter time spent on failing ART, but further studies are needed to assess the reasons behind these changes. All of the changes shown above, even the M184V decrease, were significant (p < 0.01), perhaps due to the large sample size. The NNRTI-associated mutation K103N increased from 29%–30% and Y181C decreased from 19%–12%. Several key PI associated mutations decreased to varying degrees. D30N decreased from 8%–6%; L90M from 32%–15% and 82A from 14%–8%.

Conclusions: The prevalence of some key mutations associated with ART resistance have changed significantly over the past 4 yrs, while others have remained essentially unchanged. Prescribing patterns and regimen efficacies may be key factors in these changes.