ANTIRETROVIRAL CONCENTRATIONS IN UNTIMED PLASMA SAMPLES PREDICT THERAPY OUTCOME IN A POPULATION BASED SETTING

Christopher S Alexander^1,2, Jérôme J Asselin¹, Julio SG Montaner^1,2, Lillian Ting¹, Kelly McNabb¹, P Richard Harrigan^1,2
1British Columbia Centre for Excellence in HIV/AIDS; ²University of British Columbia

Objectives: In this retrospective observational cohort study, we attempted to determine whether plasma drug levels measured in plasma samples collected for viral load testing would contribute to the prediction of response to therapy in a population-based setting of drug naïve patients initiating HAART, as previously shown for a group with more advanced HIV disease (CD4 < 50).
Method: Patients who initiated triple therapy between 08/96 and 09/99 with CD4 counts > 50 cells/mL in the province of British Columbia, Canada, were analyzed (N= 901). Plasma NNRTI and PI concentrations were retrospectively measured in the first two plasma samples collected for viral load testing up to 1 year. Drug levels were designated a priori as "low" if below the published Cmin minus one standard deviation. Mortality, HIV RNA levels, CD4 cell counts and adherence were endpoints compared for patients with abnormally low vs. normal plasma drug concentrations.
Results: Low concentrations of PI and/or NNRTIs were observed in 353 individuals (39%) at the first visit after initiating therapy (median 7 weeks). This was significantly associated with failure to achieve viral RNA < 400 c/mL in the first year of therapy (p< 0.001), as well as earlier time to CD4 failure (p< 0.001). Low drug levels in one or more plasma samples tested was strongly associated with a failure to refill antiretroviral prescription greater than 95% of the time suggesting that incomplete adherence plays a major role in these observations (p < 0.001).
Conclusions: Abnormally low PI and NNRTI concentrations in untimed plasma samples were common and this likely primarily reflects incomplete adherence in this cohort. On a population basis, abnormally low drug levels soon after starting initial HAART therapy can predict therapeutic failure.

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