To examine differences among four protease inhibitor (PI)‐based drug regimens in adherence to therapy and rate of achievement of virological suppression in a cohort of antiretroviral‐naive patients initiating highly active antiretroviral therapy (HAART).

Participants were antiretroviral‐naive and were first dispensed combination therapy containing two nucleosides and a ritonavir (RTV)‐boosted PI, or unboosted nelfinavir, between 1 January 2000 and 30 September 2003. Logistic regression analysis was used to examine associations between the prescribed PI and other baseline factors associated with being >90% adherent to therapy and then to determine the associations of prescribed drug regimen, adherence to therapy and baseline variables with the odds of achieving two consecutive viral loads of <500 HIV‐1 RNA copies/mL.

A total of 385 subjects were available for analysis. Lopinavir (LPV)/RTV was prescribed for 168 patients (42% of total); 86 (22%) received indinavir (IDV)/RTV; 91 (24%) received nelfinavir (NFV) and 40 (10%) received saquinavir (SQV)/RTV. SQV/RTV‐based HAART was associated with reduced adherence to therapy [odds ratio (OR)=0.40; 95% confidence interval (CI) 0.19–0.83]. In multivariate models, IDV/RTV (OR=0.45; 95% CI 0.22–0.92), SQV/RTV (OR=0.18; 95% CI 0.07–0.43) and NFV were associated with reduced odds of achieving virological suppression within 1 year in comparison to LPV/RTV‐based therapy. For patients receiving NFV, adjusting for adherence (OR=0.73; 95% CI 0.36–1.47) rendered this association nonsignificant.

Patients prescribed IDV/RTV, NFV or SQV/RTV were less likely to achieve virological suppression on their first regimen compared with patients prescribed LPV/RTV. Reduced adherence to these therapies only partly explained these observed differences.