Instantaneous Inhibitory Potential Is Similar to Inhibitory Quotient at Predicting HIV-1 Response to Antiretroviral Therapy

Background. 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. Methods. The correlation between differences in log(10) (IQ) (Delta log(10) (IQ))or differences in IIP (Delta IIP) 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 Delta log(10) (IQ(min)), Delta log(10) (IQ(max)), Delta IIPmin, Delta IIPmax, Delta log(10) (IQ(12)), Delta log(10) (IQ(24)), Delta IIP12, and Delta IIP24 and for comparative drugs were correlated with differences in percentage of subjects with HIV-1 RNA levels <50 copies/mL in each trial. log(10) (IQ(24)), log(10) (IQ(12)), IIP24, and IIP12 and were calculated using published median effect model slope values and t(1/2) values; r(2) values from linear regression and Spearman correlation coefficients were calculated for each analysis; and correlation coefficients were compared between log(10) (IQ) and IIP. Results. r(2) values were greatest for the Delta log(10) (IQ(12)) and Delta log(10) (IQ(24)) comparisons using intention-to-treat outcomes from the 17 trials. Differences in r(2) values between Delta log(10) (IQ(24)) and Delta IIP24 and between Delta log(10) (IQ(12)) and Delta IIP12 were 0.05 and 0.18, respectively. Differences in Spearman rank correlation coefficients between log(10) (IQ) and IIP at each drug concentration were not significantly different, with the exception of Delta log(10) (IQ(max)) and Delta IIPmax; the Delta log(10) (IQ(max)) correlation was significantly stronger than the Delta IIPmax correlation. Conclusions. IIP was not substantially better than log(10) (IQ) in describing the modest relationship between antiviral activity, pharmacokinetics, and virologic outcomes for antiretroviral drugs.