Delays in protease inhibitor use in clinical practice

Abstract

Objective: To determine the clinical factors associated with delayed protease inhibitor initiation.

Design: Chart review and telephone survey.

Setting: General medicine practice at an academic medical center in Boston, Mass.

Patients: One hundred ninety patients living with HIV and a viral load of more than 10,000 copies/ml.

Measurements and main results: The main outcome measurement was time to first protease inhibitor prescription after first elevated HIV viral load (>10,000 copies/ml). In this cohort, 190 patients had an elevated viral load (median age 39; 87% male; 12% history of injection drug use; 63% AIDS; 53% with depression; 17% history of pneumocystis pneumonia; 54% CD4 <200). In Cox proportional hazards modeling, significant univariate correlates for delayed protease inhibitor initiation were higher CD4 cell count (hazard ratio [HR] 2. 38 for CD4 200-500 compared with <200, 95% confidence interval [CI] 1.59, 3.57; and HR 8.33 for CD4> 500; 95% CI 2.63, 25.0), higher viral load (HR 0.43 for each 10-fold increase; 95% CI 0.31, 0.59), injection drug use (HR 2.08; 95% CI 1.05, 4.17), AIDS (HR 0.24; 95% CI 0.15, 0.36), and history of pneumocystis pneumonia (HR 0.32; 95% CI 0.21, 0.49). In multivariate models adjusted for secular trends in protease inhibitor use, factors significantly associated with delay of protease inhibitor initiation (p <.05) were higher CD4 cell count (for CD4 200-500, HR 2.63; 95% CI 1.61, 4.17; for CD4> 500, HR 11.11; 95% CI 3.57, 33.33), higher viral load (HR 0.66 for each 10-fold increase; 95% CI 0.45, 0.98), history of pneumocystis pneumonia (HR 0.57; 95% CI 0.37, 0.90), history of depression (HR 1. 49; 95% CI 1.03, 2.13), and history of injection drug use (HR 2.70; 95% CI 1.35, 5.56).

Conclusions: HIV-infected patients with higher CD4 cell counts or a history of depression or history of injection drug use have significant and lengthy delays of protease inhibitor therapy. Although some delays may be clinically appropriate, enhancement of provider and patient education might prove beneficial. Further research should examine reasons for delays in protease inhibitor initiation and their appropriateness.

FIGURE 1

Median days to protease inhibitor initiation for each categorical factor in the final model (unadjusted). Patients with CD4 cell counts of 200 to 500 had large absolute delays in protease inhibitor initiation when compared with patients with CD4 cell counts less than 200. Although we are unable to report an exact median number of days to protease initiation for patients with CD4 cell counts greater than 500 (owing to a large number of censored subjects), the median is at least 560 days. Similarly, patients with a history of injection drug use (IDU) and depression had large delays in protease inhibitor initiation when compared with patients without those factors. Those patients with a history of pneumocystis carinii pneumonia (PCP) were started on protease inhibitors more rapidly.