Journal Article

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

Timothy J. Henrich, Heather J. Ribaudo and Daniel R. Kuritzkes

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 51, issue 1, pages 93-98
Published in print July 2010 | ISSN: 1058-4838
Published online July 2010 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/653430
Instantaneous Inhibitory Potential Is Similar to Inhibitory Quotient at Predicting HIV-1 Response to Antiretroviral Therapy

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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 log10 (IQ) (Δlog10 (IQ)) or differences in IIP (ΔIIP) 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 Δlog10 (IQmin), Δlog10 (IQmax), ΔIIPmin , ΔIIPmax , Δlog10 (IQ12), Δlog10 (IQ24), ΔIIP12 , and ΔIIP24 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.

Results. r2 values were greatest for the Δlog10 (IQ12) and Δlog10 (IQ24) comparisons using intention-to-treat outcomes from the 17 trials. Differences in r2 values between Δlog10 (IQ24) and ΔIIP24 and between Δlog10 (IQ12) and ΔIIP12 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 Δlog10 (IQmax) and ΔIIPmax; the Δlog10 (IQmax) correlation was significantly stronger than the ΔIIPmax correlation.

Conclusions. IIP was not substantially better than log10 (IQ) in describing the modest relationship between 10 antiviral activity, pharmacokinetics, and virologic outcomes for antiretroviral drugs.

Journal Article.  3490 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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