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Relationship
between Adherence and the Development of Resistance in Antiretroviral-Naive
HIV Patients Receiving Lopinavir/Ritonavir or Nelfinavir
Relationships between adherence to protease
inhibitor (PI)-based therapy
and resistance development have not been fully characterized.
Researchers at Abbott laboratories conducted a double-blind, randomized,
controlled study of lopinavir/ritonavir
(Kaletra)
versus nelfinavir
(Viracept), each administered with
stavudine
(Zerit) and lamivudine (Epivir), 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
(Epivir) resistance, with a maximum probability
of 50% at 75%-80% adherence to nelfinavir and of 15% at 80%-85%
adherence to lopinavir/ritonavir.
In
conclusion, the authors write, “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.”
Global Pharmaceutical Research
and Development, Abbott Laboratories, Abbott Park, Illinois, USA.
05/27/05
Reference
M
S King, S C Brun and D J Kempf. Relationship between Adherence and
the Development of Resistance in Antiretroviral-Naive, HIV-1-Infected
Patients Receiving Lopinavir/Ritonavir or Nelfinavir. Journal of Infectious Diseases
191(12):2046-2052. June 15, 2005.
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