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Antimicrobial Agents and Chemotherapy, May 2008, p. 1642-1646, Vol. 52, No. 5
0066-4804/08/$08.00+0     doi:10.1128/AAC.01314-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Predictive Values of the Human Immunodeficiency Virus Phenotype and Genotype and of Amprenavir and Lopinavir Inhibitory Quotients in Heavily Pretreated Patients on a Ritonavir-Boosted Dual-Protease-Inhibitor Regimen{triangledown}

Aurélie Barrail-Tran,1 Laurence Morand-Joubert,2 Gwendoline Poizat,3 Gilles Raguin,4 Clotilde Le Tiec,1 François Clavel,5 Elisabeth Dam,5 Geneviève Chêne,3 Pierre-Marie Girard,4 Anne-Marie Taburet,1* and the Puzzle-1 (ANRS 104) Study Group

Assistance Publique hôpitaux de Paris, Hôpital Bicêtre, Service de Pharmacie Clinique, Paris, France,1 Assistance Publique hôpitaux de Paris, Hôpital Saint Antoine, Service de Bactériologie-Virologie, Paris, France,2 Inserm, U897, Université Victor Segalen Bordeaux 2, Bordeaux School of Public Health (ISPED), Bordeaux, France,3 Assistance Publique hôpitaux de Paris, Hôpital Saint Antoine, Service de Maladies Infectieuses et Tropicales, Paris, France,4 Université Paris VI, Inserm, U552, Hôpital Bichat, Assistance Publique hôpitaux de Paris, Paris, France5

Received 11 October 2007/ Returned for modification 28 November 2007/ Accepted 7 February 2008

The inhibitory quotient (IQ) of human immunodeficiency virus (HIV) protease inhibitors (PIs), which is the ratio of drug concentration to viral susceptibility, is considered to be predictive of the virological response. We used several approaches to calculate the IQs of amprenavir and lopinavir in a subset of heavily pretreated patients participating in the French National Agency for AIDS Research (ANRS) 104 trial and then compared their potentials for predicting changes in the plasma HIV RNA level. Thirty-seven patients were randomly assigned to receive either amprenavir (600 mg twice a day [BID]) or lopinavir (400 mg BID) plus ritonavir (100 or 200 mg BID) for 2 weeks before combining the two PIs. The 90% inhibitory concentration (IC90) was measured using a recombinant assay without or with additional human serum (IC90+serum). Total and unbound PI concentrations in plasma were measured. Univariate linear regression was used to estimate the relation between the change in viral load and the IC90 or IQ values. The amprenavir phenotypic IQ values were very similar when measured with the standard and protein binding-adjusted IC90s. No relationship was found between the viral load decline and the lopinavir IQ. During combination therapy, the amprenavir and lopinavir genotypic IQ values were predictive of the viral response at week 6 (P = 0.03). The number of protease mutations (<5 or ≥5) was related to the virological response throughout the study. These findings suggest that the combined genotypic IQ and the number of protease mutations are the best predictors of virological response. High amprenavir and lopinavir concentrations in these patients might explain why plasma concentrations and the phenotypic IQ have poor predictive value.

* Corresponding author. Mailing address: Pharmacie clinique, Hôpital Bicêtre, 78 rue du Général Leclerc, 94270 Kremlin Bicêtre, France. Phone: 33 1 45 21 29 57. Fax: 33 1 45 21 28 60. E-mail: anne-marie.taburet{at}bct.aphp.fr

{triangledown} Published ahead of print on 19 February 2008.

Antimicrobial Agents and Chemotherapy, May 2008, p. 1642-1646, Vol. 52, No. 5
0066-4804/08/$08.00+0     doi:10.1128/AAC.01314-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Eron, J. J. Jr., Park, J.-G., Haubrich, R., Aweeka, F., Bastow, B., Pakes, G. E., Yu, S., Wu, H., Richman, D. D., for the ACTG5126 Study Team, (2009). Predictive Value of Pharmacokinetics-Adjusted Phenotypic Susceptibility on Response to Ritonavir-Enhanced Protease Inhibitors (PIs) in Human Immunodeficiency Virus-Infected Subjects Failing Prior PI Therapy. Antimicrob. Agents Chemother. 53: 2335-2341 [Abstract] [Full Text]  


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