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

TitleInstantaneous inhibitory potential is similar to inhibitory quotient at predicting HIV-1 response to antiretroviral therapy.
Publication TypeJournal Article
Year of Publication2010
AuthorsHenrich TJ, Ribaudo HJ, Kuritzkes DR
JournalClin Infect Dis
Volume51
Issue1
Pagination93-8
Date Published2010 Jul 1
ISSN1537-6591
KeywordsAnti-HIV Agents, Antiretroviral Therapy, Highly Active, Dose-Response Relationship, Drug, HIV Infections, HIV-1, Humans, Inhibitory Concentration 50, Linear Models, Models, Biological, Randomized Controlled Trials as Topic, RNA, Viral, Statistics, Nonparametric, Viral Load
Abstract

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) (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.

RESULTS: 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.

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

DOI10.1086/653430
Alternate JournalClin. Infect. Dis.
PubMed ID20504163
PubMed Central IDPMC2880658
Grant ListK24 RR016482 / RR / NCRR NIH HHS / United States
K24 RR016482 / RR / NCRR NIH HHS / United States
K24 RR016482-09 / RR / NCRR NIH HHS / United States
P30 AI060354 / AI / NIAID NIH HHS / United States
T32 AI007387 / AI / NIAID NIH HHS / United States
T32 AI07387-19 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
UL1 RR 025758 / RR / NCRR NIH HHS / United States
UL1 RR025758 / RR / NCRR NIH HHS / United States