128. The Normalized Inhibitory Quotient (NIQ) of Lopinavir Is Predictive of Viral Load Response over 48 Weeks in a Cohort of Highly Experienced HIV-1-Infected Individuals

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Session 28 Oral Abstract Session
Pharmacology of Antiretroviral Chemotherapeutic Agents: Pharmacokinetics and Therapeutic Drug Monitoring
Session Time: Wednesday, 11:15 am - 12:30 pm
Room 6E

11:45 128.

The Normalized Inhibitory Quotient (NIQ) of Lopinavir Is Predictive of Viral Load Response over 48 Weeks in a Cohort of Highly Experienced HIV-1-Infected Individuals
A. Castagna*¹, A. Danise¹, H. Hasson¹, E. Boeri¹, A. Lazzarin¹, M. Peeters², S. Piscitelli², and R. Hoetelmans²
¹Hosp. San Raffaele, Milan, Italy and ²Tibotec-Virco, Rockville, MD, and Mechelen, Belgium

Background: Resistance testing provides information on the susceptibility of a patient’s HIV-1 to antiretrovirals. However, it does not incorporate exposure to drugs needed to suppress replication. In this study we examined the relationship between viral susceptibility, drug exposure, and the combination of these, the normalized inhibitory quotient (NIQ, individually determined ratio of trough concentration/fold change of VirtualPhenotype (vPT), divided by the fixed ratio of mean trough concentration in the population/cut-off for resistance for vPT) and virologic outcome in a cohort of experienced HIV-1-infected patients treated with Kaletra (LPV/r) over 48 weeks.
Methods: In a cohort of HIV-1-infected patients who failed previous PI-based regimens, LPV/r was initiated with a backbone of antiretrovirals chosen by the physician. The vPT was determined at baseline, and plasma concentrations of all antiretrovirals 12 hours after last intake of LPV/r were determined during steady-state. Viral load (VL) response over 48 weeks after start of LPV/r was correlated with baseline VL, vPT for LPV, LPV trough concentration, and LPV NIQ, using linear regression analysis and mixed-effects models.
Results: The LPV vPT, LPV trough, and VL data were collected in a cohort of 55 patients. The median BL VL was 4.89 log. Overall median change in VL from BL was 1.5 log at week 4, and 1.9, 1.6, and 1.4 log at week 12, 24, and 48, respectively (data for 52, 48, 52, and 35 patients available, respectively). In a univariate linear regression analysis, baseline VL, LPV vPT, and LPV NIQ were associated with change in VL from baseline at several time points. In a mixed-effects model, only baseline VL (p<0.0001) and LPV NIQ (p=0.0008) were associated with change in VL from baseline over 48 weeks. When divided in 4 equal groups based on LPV NIQ, patients with a LPV NIQ < 0.6 had a median VL drop of 0.7 log after 48 weeks, while this was 1.1, 1.5, and 2.8 log if the LPV NIQ was between 0.6-2.6, 2.6-14.5, or >14.5, respectively (p=0.009).
Conclusions: In this cohort of highly experienced patients treated with LPV/r, baseline VL, and LPV NIQ were predictive of virologic response over 48 weeks. The NIQ was more predictive than resistance testing or drug exposure alone. These results confirm the relevance of integrating resistance testing and drug exposure on an individual basis, and warrant prospective studies to test the concept of inhibitory quotients as a tool to improve response to therapy.