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.