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J Infect Dis. 2005 Jun 15;191(12):2046-52. Epub 2005 May 12.

Relationship between adherence and the development of resistance in antiretroviral-naive, HIV-1-infected patients receiving lopinavir/ritonavir or nelfinavir.

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  • 1Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA. martin.king@abbott.com

Abstract

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.

PMID:
15897990
[PubMed - indexed for MEDLINE]
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