Evidence map›Paper›PMID 20504163›Full record

ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2010

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

Timothy J Henrich, Heather J Ribaudo, Daniel R Kuritzkes

Abstract read
In one paragraph

Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Dose-response curve slope is a missing dimension in the analysis of HIV-1 drug resistance.Proceedings of the National Academy of Sciences of the United States of America · 2011
    Article
  5. Review
  6. Review
  7. Achieving a quantitative understanding of antiretroviral drug efficacy.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2010
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors.

Timothy J HenrichDivision of Infectious Disease, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Heather J Ribaudo
Daniel R Kuritzkes

Funding

AIDS Clinical Trials Group NetworkU01AI068636 · NIAID · SOCIAL AND SCIENTIFIC SYSTEMS, INC. · PI KURITZKES, DANIEL R. · 2006 to 2010
$147.1M
The impact of HIV viral diversity and cellular immunity on HIV pathogenesisP30AI060354 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Daniel Lingwood · 2004 to 2026
$94.4M
HARVARD CLINICAL AND TRANSLATIONAL SCIENCE CENTER (UL1)UL1RR025758 · NCRR · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2008 to 2011
$91.4M
Multidisciplinary HIV Training ProgramT32AI007387 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI Daniel R. Kuritzkes · 1990 to 2026
$8.8M
Harvard Clinical and Translational Science Center (KL2)KL2RR025757 · NCRR · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2008 to 2011
$4.1M
HIV-1 THERAPEUTICS AND DRUG RESISTANCEK24RR016482 · NCRR · UNIVERSITY OF COLORADO DENVER · PI KURITZKES, DANIEL R. · 2001 to 2010
$1.0M
NCRR NIH HHS K24 RR016482NCRR NIH HHS KL2 RR025757NCRR NIH HHS UL1 RR 025758NCRR NIH HHS UL1 RR025758NIAID NIH HHS P30 AI060354NIAID NIH HHS T32 AI007387NIAID NIH HHS T32 AI07387-19NIAID NIH HHS U01 AI068636
6 · The paper itself

Abstract

backgroundThe 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.

methodsThe 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.

resultsr2 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.

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

Indexed as

Antiretroviral Therapy, Highly ActiveInhibitory Concentration 50Models, BiologicalAnti-HIV AgentsDose-Response Relationship, DrugHIV-1HIV InfectionsHumansLinear ModelsRandomized Controlled Trials as TopicRNA, ViralStatistics, NonparametricViral LoadAnti-HIV AgentsRNA, Viral

Identifiers

PMID20504163
PMCPMC2880658

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.