577 Relationships among Four Measures of Medication Adherence and Virologic Response in ACTG 359 C.V. Fletcher*1, M.A. Testa2, R. Haubrich3, R. Brundage4, H. Jiang2, J. Ickovics5, A. Martinez6, S. Snyder7, R. Gulick8 1Univ of Colorado Hlth Sci Ctr, Denver; 2Harvard Sch of Public Hlth, Boston, MA; 3Univ of California at San Diego; 4Univ of Minnesota, Minneapolis; 5Yale Sch of Med, New Haven, CT; 6Div of Acquired Immunodeficiency Syndrome, Rockville, MD; 7Social and Sci Sys, Silver Spring, MD; and 8Weill Med Coll of Cornell Univ, New York, NY
Background: Medication adherence is a critical determinant of antiretroviral drug effectiveness, yet the optimal way to assess patient adherence is unknown. We studied 3 measures of adherence, and quantified drug concentrations in ACTG 359, a study of saquinavir soft gel (SQV) with ritonavir or nelfinavir, together with delavirdine, adefovir, or both in indinavir-experienced persons.
Methods: Evaluations were: 1) Week 0 to 4 medication count (MC) of remaining SQV capsules (n = 220); 2) Overall regimen adherence estimated from 2-day, self-report (SELFRPT) of proportion of pills skipped averaged across all drugs at wks 4, 8, and 16 (n = 258); 3) Therapeutic coverage as the % of time over 24 hrs that medication coverage was maintained using MEMS caps applied to SQV bottles (n = 62); and 4) SQV 24 hr area under the curve (AUC) estimated from random samples at wks 4, 8, and 16 (n = 186). The primary virologic endpoint was the wk 16 HIV RNA.
Results: Thirty percent (30%) of 254 subjects had HIV RNA = 500 cpm at wk 16. Median MC for SQV was 18 caps, or approx 1.5 days of therapy. Mean (SE, median, 25th percentile) for SELFRPT, MEMS and AUC were 0.82 (0.02, 1.0, 0.75), 0.64 (0.032, 0.72, 0.47) and 20.4 mg*h/L (1.13, 15.9, 10.2). All pair wise correlations among the 4 measures were non significant (p > 0.10). Measures weakly associated with the wk 16 change in log RNA were SELFRPT (rho = -0.15, p = 0.019, n = 244) and the SQV AUC (rho = -0.17, p = 0.023, n=180). Subjects with wk 16 HIV RNA = 500 or > 500 cpm differed significantly in SELFRPT and AUC measures (Mann-Whitney test, p = 0.03 and 0.008, respectively). Logistic regression also showed SELFRPT and AUC to be significant predictors of response after adjusting for treatment effect, with SELFRPT > 95% increasing the odds of virologic success (RNA = 500 cpm) by approx 86% (p = 0.044) and AUC increasing the odds of success by approx 3.5% per unit increase in AUC (p = 0.004).
Conclusions: This is the first concurrent evaluation of 4 putative measures of medication adherence. The lack of an association with MEMS contrasts with the findings of others. SELFRPT was a significant predictor of virologic response. SQV AUC, derived from measured concentrations on 3 separate occasions, also predicted virologic response. These evaluations provide insight into methods to assess and improve adherence.
