Abstract
OBJECTIVE: We compared the rate of emergence of thymidine analogue mutations (TAMs) and major protease inhibitor mutations in adherent patients who remained on stable treatment with a thymidine analogue and/or protease inhibitor after the onset of virologic failure. DESIGN: Follow-up genotypic resistance testing was done using archived plasma obtained from patients having 0 or 1 TAM and/or 0 or 1 major protease inhibitor resistance mutation at the onset of virologic failure. RESULTS: The median duration of observed failure was 691 days. There were 41 thymidine analogue regimens and 34 protease inhibitor regimens; concomitant ritonavir was used 4 times. New major protease inhibitor mutations emerged more rapidly than did new TAMs (P = 0.0019); new TAMs emerged more rapidly in thymidine analogue regimens that did not include lamivudine (P = 0.0073). The emergence of TAMs and major protease inhibitor mutations did not differ if lamivudine was not part of the thymidine analogue regimen. The evolution of CD4 cell counts and plasma viral loads (pVLs) during virologic failure was similar regardless of whether or not a new TAM or major protease inhibitor mutations emerged or, for thymidine analogue-containing regimens, whether lamivudine was or was not used. CONCLUSIONS: Major protease inhibitor mutations arose more frequently and rapidly than did TAMs in patients with sustained virologic failure who received lamivudine.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 541-549 |
| Number of pages | 9 |
| Journal | Journal of Acquired Immune Deficiency Syndromes |
| Volume | 43 |
| Issue number | 5 |
| DOIs | |
| State | Published - Dec 2006 |
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Keywords
- HIV resistance
- Protease inhibitors
- Resistance mutations
- Reverse transcriptase inhibitors
ASJC Scopus subject areas
- Virology
- Immunology
Cite this
Evolution of HIV resistance mutations in patients maintained on a stable treatment regimen after virologic failure. / Goetz, Matthew Bidwell; Ferguson, Monique; Han, Xueliang; McMillan, Greg; Clair, Marty St; Pappa, Keith A.; McClernon, Daniel R.; O'Brien, William A.
In: Journal of Acquired Immune Deficiency Syndromes, Vol. 43, No. 5, 12.2006, p. 541-549.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Evolution of HIV resistance mutations in patients maintained on a stable treatment regimen after virologic failure
AU - Goetz, Matthew Bidwell
AU - Ferguson, Monique
AU - Han, Xueliang
AU - McMillan, Greg
AU - Clair, Marty St
AU - Pappa, Keith A.
AU - McClernon, Daniel R.
AU - O'Brien, William A.
PY - 2006/12
Y1 - 2006/12
N2 - OBJECTIVE: We compared the rate of emergence of thymidine analogue mutations (TAMs) and major protease inhibitor mutations in adherent patients who remained on stable treatment with a thymidine analogue and/or protease inhibitor after the onset of virologic failure. DESIGN: Follow-up genotypic resistance testing was done using archived plasma obtained from patients having 0 or 1 TAM and/or 0 or 1 major protease inhibitor resistance mutation at the onset of virologic failure. RESULTS: The median duration of observed failure was 691 days. There were 41 thymidine analogue regimens and 34 protease inhibitor regimens; concomitant ritonavir was used 4 times. New major protease inhibitor mutations emerged more rapidly than did new TAMs (P = 0.0019); new TAMs emerged more rapidly in thymidine analogue regimens that did not include lamivudine (P = 0.0073). The emergence of TAMs and major protease inhibitor mutations did not differ if lamivudine was not part of the thymidine analogue regimen. The evolution of CD4 cell counts and plasma viral loads (pVLs) during virologic failure was similar regardless of whether or not a new TAM or major protease inhibitor mutations emerged or, for thymidine analogue-containing regimens, whether lamivudine was or was not used. CONCLUSIONS: Major protease inhibitor mutations arose more frequently and rapidly than did TAMs in patients with sustained virologic failure who received lamivudine.
AB - OBJECTIVE: We compared the rate of emergence of thymidine analogue mutations (TAMs) and major protease inhibitor mutations in adherent patients who remained on stable treatment with a thymidine analogue and/or protease inhibitor after the onset of virologic failure. DESIGN: Follow-up genotypic resistance testing was done using archived plasma obtained from patients having 0 or 1 TAM and/or 0 or 1 major protease inhibitor resistance mutation at the onset of virologic failure. RESULTS: The median duration of observed failure was 691 days. There were 41 thymidine analogue regimens and 34 protease inhibitor regimens; concomitant ritonavir was used 4 times. New major protease inhibitor mutations emerged more rapidly than did new TAMs (P = 0.0019); new TAMs emerged more rapidly in thymidine analogue regimens that did not include lamivudine (P = 0.0073). The emergence of TAMs and major protease inhibitor mutations did not differ if lamivudine was not part of the thymidine analogue regimen. The evolution of CD4 cell counts and plasma viral loads (pVLs) during virologic failure was similar regardless of whether or not a new TAM or major protease inhibitor mutations emerged or, for thymidine analogue-containing regimens, whether lamivudine was or was not used. CONCLUSIONS: Major protease inhibitor mutations arose more frequently and rapidly than did TAMs in patients with sustained virologic failure who received lamivudine.
KW - HIV resistance
KW - Protease inhibitors
KW - Resistance mutations
KW - Reverse transcriptase inhibitors
UR - http://www.scopus.com/inward/record.url?scp=33845371783&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33845371783&partnerID=8YFLogxK
U2 - 10.1097/01.qai.0000245882.28391.0c
DO - 10.1097/01.qai.0000245882.28391.0c
M3 - Article
C2 - 17075391
AN - SCOPUS:33845371783
VL - 43
SP - 541
EP - 549
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
SN - 1525-4135
IS - 5
ER -