O2 Comparison of viral drug resistance, adherence and PK indices in patients on successful and failing PI-based regimens

Abstract

Objective: To evaluate the contributions of the above parameters to failure of PI-based antiretroviral therapy. Methods: Patients on their first PI-based combination were divided into cases (HIV VL > 1000 copies/mL) and controls (VL < 50 copies/mL). The following were compared: (1) treatment adherence measured objectively by MEMS Cap (MC) and by patient questionnaire; (2) random, trough and 4-h PI plasma; (3) viral genotype and phenotype at time of recruitment (cases only). Results: Median self-reported adherence over the preceding month was significantly lower among cases (96.7%; range 50–100%; n = 26) than controls (100%; range 90.7–100%; n = 10; P < 0.02) and there was a trend to lower median adherence as measured by MC (98.2% (range 25.6–107.9%) vs. 100.9% (range 82.6–107.8%), respectively; P = 0.14); 42.3% of cases and 20% of controls displayed adherence < 95% on MC. Twenty-one per cent of cases had no detectable protease resistance mutations, while 57% displayed typical resistance patterns and 21% polymorphisms only. Lower adherence was associated with detection of fewer resistance mutations (P = 0.047). PK data will be presented. Conclusion: Failure of HAART is a complex phenomenon. A minimum level of adherence may be required to drive the emergence of viral resistance. Cases reported lower adherence than controls, but objectively the difference was less marked.