The use of virtual inhibitory quotient (VIQ) in antiretroviral (ART) experienced patients taking amprenavir/lopinavir combinations
Phillips, E., Tseng, A., Walker, S., Loutfy, M., Walmsley, S., Tailor, S. and Harrigan, P.R. (2002) The use of virtual inhibitory quotient (VIQ) in antiretroviral (ART) experienced patients taking amprenavir/lopinavir combinations. In: 9th Conference on Retroviruses and Opportunistic Infections, 24 - 28 February 2002, Seattle, U.S.A.
Background: There is increasing evidence to suggest that drug levels of protease inhibitors (Pis) correlate with virologic outcome. The appropriate application of VIQ (C min/(virtual phenotype [VP] fold change x protein corrected EC 50 for wildtype) has not been defined. VIQ may be a more useful measurement than drug levels alone in ART experienced patients since it incoporates VP as a measure of drug resistance.
Methods: To explore relationships between VIQ and virologic outcome, we measured pre- and post-PI levels in 16 ART, PI-experienced patients who had been tolerating amprenavir/lopinavir/ritonavir combinations for at least 3 months (median = 5 months, median baseline viral load [VL] = 107,035 copies/mL). VIQs were calculated from the VPs of amprenavir and lopinavir prior to starting therapy (VIRCO, UK) and the measured C min of amprenavir and lopinavir, respectively.
Results: 6/16 patients had a nondetectable VL (<50 copies/mL) at the time levels were measured while 10/16 had VL > 50 copies/mL. The median Cmins for amprenavir and lopinavir were 1085 ng/mL (219-1997 ng/mL) and 3272 ng/ml (1901-6553 ng/mL) respectively. For amprenavir the median VIQ was significantly higher in the group with VL < 50 copies/mL (VIQ = 2.58 [1-9.08]) vs those with VL > 50 copies/mL (VIQ = 0.62 [0.03-2.25]), p=0.013 (Mann Whitney U). For lopinavir there was a trend towards a higher median VIQ in the group with VL < 50 copies/mL (VIQ = 12.2 [2.73-112.7]) vs those with VL > 50 (VIQ = 1.82 [0.33-11.4]), p=0.076 (Mann Whitney U). 83% (5/6) of those with undetectable VLs (<50 copies/mL) had lopinavir VIQ > 15 and/or amprenavir VIQ > 1.3 vs only 2/10 (20%) of those with VL > 50 copies/mL (p=0.01, chi).
Conclusions: For treatment experienced patients initiating amprenavir/lopinavir combinations, VIQ may be a potentially useful tool to identify those at risk for treatment failure with conventional dosing.
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