Instantaneous inhibitory potential is similar to inhibitory quotient at predicting HIV-1 response to antiretroviral therapy.

Abstract

The instantaneous inhibitory potential (IIP), a measure of antiviral activity that incorporates the slope of the dose-response curve, has been proposed as a better predictor of clinical efficacy than the inhibitory quotient (IQ). However, there are no quantitative analyses supporting this hypothesis. The correlation between differences in log10(IQ) (Deltalog10(IQ)) or differences in IIP (DeltaIIP) and the differences in percentage of subjects with plasma human immunodeficiency virus type 1 (HIV-1) RNA levels <50 copies/mL at week 48 was determined for antiretroviral drugs compared in 17 randomized clinical trials. The Deltalog10(IQmin), Deltalog10(IQmax), DeltaIIPmin, DeltaIIPmax, Deltalog10(IQ12), Deltalog10(IQ24), DeltaIIP12, and DeltaIIP24 for comparative drugs were correlated with differences in percentage of subjects with HIV-1 RNA levels <50 copies/mL in each trial. log10(IQ24), log10(IQ12), IIP24, and IIP12 were calculated using published median effect model slope values and t1/2 values; r2 values from linear regression and Spearman correlation coefficients were calculated for each analysis; and correlation coefficients were compared between log10(IQ) and IIP. r2 values were greatest for the Deltalog10(IQ12) and Deltalog10(IQ24) comparisons using intention-to-treat outcomes from the 17 trials. Differences in r2 values between Deltalog10(IQ24) and DeltaIIP24 and between Deltalog10(IQ12) and DeltaIIP12 were 0.05 and 0.18, respectively. Differences in Spearman rank correlation coefficients between log10(IQ) and IIP at each drug concentration were not significantly different, with the exception of Deltalog10(IQmax) and DeltaIIPmax; the Deltalog10(IQmax) correlation was significantly stronger than the DeltaIIPmax correlation. IIP was not substantially better than log10(IQ) in describing the modest relationship between antiviral activity, pharmacokinetics, and virologic outcomes for antiretroviral drugs.