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Session 127 Poster Abstracts
Diagnostics: Measuring the Consequences of Antiretroviral Therapy
Friday, 1:30 - 3:30 pm
Hall A


745    
Use of Bilirubin as a Surrogate Marker of Medication Adherence to Atazanavir-based ART
Kyle Petersen*1,3, B Hale2,4, L Jones1,3, A Christensen2,4, M Riddle5, M Bavaro2,4, and S Tasker1,3
1Natl Naval Med Ctr, Bethesda, MD, USA; 2Triservice AIDS Clin Consortium, San Diego, CA, USA; 3Triservice AIDS Clin Consortium, San Diego, CA, USA; 4Naval Med Ctr, San Diego, CA, USA; and 5Naval Med Res, Cairo, Egypt

Background:  Poor adherence to ART is the most important factor contributing to virologic failure and HIV resistance. Using biochemical markers like mean corpuscular volume (MCV) to monitor adherence is simple and inexpensive. Increased MCV has a sensitivity of 80% and specificity of 44% for adherence to zidovudine- (AZT) or stavudine- (d4T) based regimens, but many newer once-daily regimens lack AZT or d4T, limiting use of MCV as a marker of adherence. Atazanavir (TAZ) raises bilirubin in 83% of patients. We explored the use of bilirubin as a marker of adherence in TAZ-containing regimens.

Methods:  Retrospective chart review of 92 patients on TAZ-based ART to determine bilirubin, CD4, and viral load before start of ART and at subsequent follow-ups. Durability of bilirubin rise at subsequent follow-up and effect of ritonavir on bilirubin were also studied.

Results:  Of the 92 patients, 78 met criteria for inclusion. Mean age was 39; 67% were male; baseline CD4 was 284; and median viral load was 10,000 copies/mL. Median baseline bilirubin was 0.5. Patients had taken a median of 8 ART agents previously. Median first follow-up occurred at 57 days. There was a mean decrease in viral load at first follow-up of 1.4 log (95% CI 0.8 to 2.0). Bilirubin increased by a median of 0.4. Using a 2-log drop as a marker for successful suppression, 41% of patients were suppressed at first follow-up. Association of bilirubin increase with successful viral suppression showed a statistically significant difference in bilirubin rise among responders compared to non-responders (2-sample Wilcoxon rank-sum, p = 0.001). Median bilirubin increase (IQR) for patients achieving successful viral suppression was 1.0 (0.4 to 1.9), compared with 0.2 (0.1 to 0.9) for those not achieving viral suppression. With a 2-log drop in viral load, bilirubin levels had various sensitivity and specificities as shown in the table.

 

Cut-point

Sensitivity

95% C.I.

Specificity

95% C.I.

≥ 0.2

84

67–95

48

33–63

≥ 0.3

81

64–93

61

45–75

≥ 0.4

75

57–89

65

50–79

≥ 0.5

66

47–81

67

52-80

 

Conclusions:  Our results suggest that bilirubin increase ³. 0.3 may be a good marker for adherence to TAZ (sensitivity 81%, specificity 61%). Further studies are required including a larger population cohort, longer follow-up time and determination of confounders such as Gilbert’s disease to confirm the use of bilirubin increase to measure TAZ adherence.

 

Keywords: adherence; atazanavir; bilirubin