Relationship between adherence and the development of resistance in antiretroviral-naive, HIV-1-infected patients receiving lopinavir/ritonavir or nelfinavir.
BACKGROUND
Relationships between adherence to protease inhibitor (PI)-based therapy and resistance development have not been fully characterized.


METHODS
We conducted a double-blind, randomized, controlled study of lopinavir/ritonavir versus nelfinavir, each administered with stavudine and lamivudine, in 653 antiretroviral-naive, human immunodeficiency virus (HIV)-1-infected patients. Relationships between adherence and probability of resistance development were evaluated by local linear regression or logistic regression.


RESULTS
A higher risk of detectable HIV-1 RNA loads after week 24 was associated with lower adherence (odds ratio [OR], 1.08 per 1% decrease in adherence [95% confidence interval {CI}, 1.05-1.10]; P<.001) and nelfinavir use (OR, 2.4 vs. lopinavir/ritonavir [95% CI, 1.6-3.6]; P<.001). Among all nelfinavir-treated patients, a bell-shaped relationship between adherence and the risk of nelfinavir resistance was observed, with a maximum probability of 20% at 85%-90% adherence. No lopinavir resistance was observed. A bell-shaped relationship was also observed for the probability of lamivudine resistance, with a maximum probability of 50% at 75%-80% adherence to nelfinavir and of 15% at 80%-85% adherence to lopinavir/ritonavir.


CONCLUSIONS
Bell-shaped relationships between adherence and resistance were observed. Irrespective of adherence level, the risk of detectable HIV-1 RNA loads or of PI or lamivudine resistance was significantly higher in nelfinavir-treated patients than in lopinavir/ritonavir-treated patients.
King
Martin S
MS
Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA. martin.king@abbott.com
Brun
Scott C
SC
Kempf
Dale J
DJ
D004311:Double-Blind Method; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage*; D006801:Humans; D061466:Lopinavir; D019888:Nelfinavir / Q000008:administration & dosage; D016017:Odds Ratio; D010349:Patient Compliance; D011744:Pyrimidinones / Q000008:administration & dosage; D012367:RNA, Viral / Q000097:blood; D012307:Risk Factors; D019438:Ritonavir / Q000008:administration & dosage; D019562:Viral Load
D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D012367:RNA, Viral; D061466:Lopinavir; D019888:Nelfinavir; D019438:Ritonavir