Percentage of adherence correlates with the risk of protease inhibitor (PI) treatment failure in HIV-infected patients

Objectives: To determine the effect of adherence on the rate of protease inhibitor (PI) treatment failure among human immunodeficiency virus (HIV)-infected patients. Methods: A prospective study of a cohort of 282 patients who initiated PI therapy from March 1996 to December 1997. Adherence was quantified as the percentage of prescribed doses reportedly taken and treatment failure was defined as HIV RNA levels above 200 copies/ml after 1 year on therapy. Results: Overall, 190 patients (67%) missed prescribed doses. However, mean percentage of doses taken was 91% (range, 21-100%). Demographic, virological and immunological characteristics could not predict adherence outcomes. The causes of non-adherence included intolerance or side effects (35%), complexity of treat-ment (23%), or recurrence in active drug abuse (17%), whereas abandonment owing to HIV-related disease was uncommon (6%). A degree of adherence above 90% correlated significantly with viral suppression [relative risk (RR) 1.69; 95% confidence interval (CI) 1.1-2.56; P<0.01]. In a multivariate analysis, a lower degree of adherence (RR, 0.96; P=0.006), a higher HIV viral load (RR, 2.03; P=0.0001), prior antiretroviral therapy (RR, 2.5; P=0.01), and use of saquinavir-hard gel capsules (saquinavir-HGC) (RR, 1.77; P=0.03) were strongly associated with treatment failure. Conclusion: The percentage of adherence and initial HIV viral load are the most important determinants of virological response to PI therapy and non-adherence is related to treatment-related factors in the majority of cases.